Yourlawyer.com (Accutane News)

Accutane Pulled from Market Amid Lawsuits, Increased Generic Competition

Mon, 29 Jun 2009 00:00:00 -0700

Accutane is being pulled from the market by its maker, Roche AG. According to the Associated Press, Roche said the decision to withdraw Accutane was made for economic rather than safety reasons. But as anyone who reads this blog known, over the past couple of years, Roche has lost several Accutane lawsuits, and been ordered to pay more than $33 million to people who claim they were injured by the drug.

Approved by the Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to hundreds of cases of suicide in the United States. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.

Most recently, Roche lost several Accutane lawsuits brought by people who claimed the drug caused them to develop inflammatory bowel disease (IBD). In November 2008, a New Jersey jury ordered the company to pay $13 million to three such plaintiffs. The previous April, another New Jersey jury awarded $10.5 million to a woman who blamed the drug for her ulcerative colitis. In May 2007, another New Jersey trial resulted in an award of $2.62 million to a patient who needed to have his colon and most of his rectum removed after taking the drug. In October that same year, a Florida jury awarded $7 million in damages to another Accutane user who developed the IBD.

In announcing its decision to pull Accutane, Roche did cite the high cost of product liability suits - it currently faces 5000 such lawsuits - involving the drug. But according to Bloomberg.com, the company also said a reevaluation of its product line had shown Accutane faced serious competition from generics.

Roche said Accutane will be pulled in the U.S. and 11 other countries. The last date for distribution in the United States was June 25. According to Reuters, Accutane is now no longer available from Roche directly but patients may still be able to get it from pharmacies.

Study Links Accutane to Depression

Thu, 29 May 2008 00:00:00 -0700

The active ingredient in the acne drug Accutane— known generically as isotretinoin—more than doubles the risk of depression, according to a recent study. The study is the first controlled investigation to find a statistically significant link between Accutane and depression, Dr Anick Berard, from CHU Sainte-Justine Research Centre in Montreal, and colleagues, state in a report in the Journal of Clinical Psychiatry. “Current guidelines should possibly be modified to include psychiatric assessments of patients prior to and during isotretinoin therapy," the researchers wrote.

Berard's team studied 30,496 people from Quebec, Canada, who received at least one Accutane or isotretinoin prescription from 1984 through 2003. During the study period, 126 of these individuals received a depression-related diagnosis, hospitalization, or treatment. Also, based on earlier research, the researchers focused on isotretinoin use in the five months prior to the depression diagnosis—the risk period—as compared with a five-month period a year before the diagnosis—the control period. After accounting for potential factors that might influence the results, isotretinoin exposure was associated with a greater than 2.6-fold relative risk of depression, the team found. "Because depression could have serious consequences, close monitoring of isotretinoin users is indicated," Berard and colleagues concluded.

Suicide is common in the US, representing the fourth leading cause of death for those aged 18 to 65 and the third leading cause for those aged 15 to 24. Add to those figures the complexity of medications. And recently, reports have been filed with drug makers and the Food and Drug Administration (FDA) on at least six drugs or drug classes that may be linked to suicide or suicidal thoughts; the acne drug, Accutane, is among these.

Recently, the Food & Drug Administration (FDA) released notices about several such medications including Singlulair; epilepsy drugs including carbamazepine, gabapentin, felbamate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, and valproate; and the smoking-cessation drug Chantix. Reports have been filed on SSRI antidepressants including Paxil and Prozac, the influenza drug Tamiflu, and the acne medicine Accutane. "The brain is a complex organ, and most of the drugs are complex as well,’’ says Dr. Thomas Laughren, head of the division of psychiatric products at the FDA. "It’s not unreasonable to think that a drug that gets into the brain may have effects other than you hope they would.’’

Kelly Posner, principal investigator at the Center for Suicide Risk Assessment at Columbia University in New York, is working with the FDA to determine suicide risks and at-risk categories; Posner’s quantitative tools and questionnaires are being applied to drugs on the market and in testing. "We know that whether or not these drugs actually cause suicidal thought or action is a question we have to answer, but up until now, none of the clinical trials for the drugs were set up to address the question,’’ says Posner.

Meanwhile, Congressman Bart Stupak (Democrat-Michigan) reported his teenage son B.J. killed himself in 1999 after several months on Accutane and said in 1998, the FDA publicly noted reports of depression, psychosis, and suicidal thoughts and actions with Accutane; in 1999 when B.J. was prescribed Accutane, their doctor did not inform them of the risk and the prescription’s patient information did not include it.

Many Popular Drugs Linked to Suicide

Thu, 08 May 2008 00:00:00 -0700

Suicide is common in the US, representing the fourth leading cause of death for those aged 18 to 65 and the third leading cause for those aged 15 to 24. Add to those figures the complexity of medications. In recent years, disturbing reports have suggested that side effects of some popular drugs - such as Chantix, Accutane, Singular and Paxil - include suicidal thoughts and behavior.

Reports have been filed with drug makers and the Food and Drug Administration (FDA) on at least six drugs or drug classes that may be linked to suicide or suicidal thoughts. Recently, the FDA released notices about several such medications including Singlulair; Epilepsy drugs including carbamazepine, gabapentin, felbamate, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, and valproate; and the smoking-cessation drug Chantix. Reports have been filed on SSRI antidepressants including Paxil and Prozac, the influenza drug Tamiflu, and the acne medicine Accutane. "The brain is a complex organ, and most of the drugs are complex as well,’’ says Dr. Thomas Laughren, head of the division of psychiatric products at the FDA. "It’s not unreasonable to think that a drug that gets into the brain may have effects other than you hope they would.’’

Kelly Posner, principal investigator at the Center for Suicide Risk Assessment at Columbia University in New York, is working with the FDA to determine suicide risks and at-risk categories; Posner’s quantitative tools and questionnaires are being applied to drugs on the market and in testing. "We know that whether or not these drugs actually cause suicidal thought or action is a question we have to answer, but up until now, none of the clinical trials for the drugs were set up to address the question,’’ says Posner.

There are theories, says Jason Noel, director of clinical pharmacy services at Rosewood Center in Owings Mills, Maryland. Asthma medication Singulair has a similar chemical pathway to steroids, which can affect behavior and mood and an asthma diagnosis can trigger suicide or depression because it adversely affects daily living. Fatigue is a symptom of depression, the initial benefit of antidepressants is increased energy, and improving depression can take weeks; therefore, some may use extra energy to act on suicidal thoughts. Suicidal thoughts in patients taking epilepsy drugs have been reported in patients on such medications for epilepsy, depression, or other psychiatric conditions; however, not generally in those on the drugs for migraines. Chantix blocks pleasure pathways that make nicotine so satisfying, which suppresses other pleasure and happiness, leading to depression. But, stopping smoking can be a risk factor for depression and smoking is a risk factor for suicide.

Finding links has risks. When the FDA discovered an increase in suicidal thinking in children and young adults taking antidepressants, warnings were added to Paxil and Prozac labeling. "Use of antidepressants went down and the suicide rate went up,’’ says Dr. Paula Clayton, medical director of the American Foundation for Suicide Prevention in New York.

Meanwhile, Congressman Bart Stupak (Democrat-Michigan) reported his teenage son B.J. killed himself in 1999 after several months on Accutane and said in 1998, the FDA publicly noted reports of depression, psychosis, and suicidal thoughts and actions with Accutane; in 1999 when B.J. was prescribed Accutane, their doctor did not inform them of the risk and the prescription’s patient information did not include it.

Accutane Injury Results in $10.5 Million Judgment

Wed, 23 Apr 2008 00:00:00 -0700

A woman who said she developed ulcerative colitis from taking Accutane was awarded $10.5 million by a New Jersey jury yesterday. It was the third of 425 lawsuits alleging that Accutane caused inflammatory bowel disease in some users to go to trial. All three cases have resulted in multi-million dollar judgments against Hoffman-LaRoche, Inc., the maker of Accutane.

Approved by the Food & Drug Administration (FDA) in 1982, Accutane has been the subject of controversy for years. In addition to inflammatory bowel disease, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. In addition to inflammatory bowel disease, Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.

Inflammatory bowel disease refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. In ulcerative colitis, the inner lining of the intestine becomes inflamed and develops ulcers. Ulcerative colitis is often the most severe in the rectal area, which can cause frequent diarrhea. Mucus and blood often appear in the stool if the lining of the colon is damaged.

According to the Wall Street Journal, Kamie Kendall, a 24-year-old Utah hairdresser, started taking Accutane at age 12. She was diagnosed with ulcerative colitis at the age of 14, and in 2006 she had her colon removed and now suffers from debilitating diarrhea. The jury awarded Kendall $10.5 million of compensatory damages plus $78,500 for medical expenses. The judge presiding over the case ruled there was insufficient evidence to allow the jury to consider punitive damages or consumer fraud.

Kendall is the third Accutane plaintiff to successfully sue Hoffman-LaRoche over inflammatory bowel disease. In May, another New Jersey jury awarded $2.62 million in damages to a patient who needed to have his colon and most of his rectum removed after taking the drug Accutane. In October, A Florida jury awarded $7 million in damages to another Accutane user who developed the disorder and said Hoffman-LaRoche failed to adequately warn of the drug's risks.

Hoffman-LaRoche has said it will appeal all of the verdicts, and insisted that the link between Accutane and inflammatory bowel disease has not yet been proven. In a statement, the company also said that "the Accutane labeling has contained a warning about IBD for more than 20 years."

Accutane Access Now Easier With Changes to iPledge

Thu, 06 Dec 2007 00:00:00 -0800

Accutane prescriptions might now be a little easier for women to fill. The government announced some changes Wednesday designed to ease access to the drug. A program entitled iPledge-a risk management program designed to reduce the risk of fetal exposure to isotetinoin (Accutane) prescribed for the treatment of severe recalcitrant nodular acne-was amended to ensure that every user of Accutane (or its generic substitutes), every doctor who prescribes it, and every pharmacy that sells it follow strict rules ensure sure women do not become pregnant while on the drug. Among those rules are month-by-month prescriptions based on monthly pregnancy tests.

But last summer, the Food and Drug Administration (FDA) heard evidence that iPledge has not ended the problem. There were 122 pregnancies in the program's first year and another 37 in the four months since. Another 19 pregnancies occurred in women who managed to get the drug despite never enrolling in iPledge. Despite this, in October, the FDA agreed to a few changes, announcing Wednesday that iPledge is now implementing these changes. Women of childbearing age who do not fill a prescription within seven days of a pregnancy test will be allowed to get another test and then fill the prescription, with the exception of the initial prescription. Until now, those who didn't act within seven days were frozen out of the program for the next 23 days. Those women will have to fill the prescription within seven days of a pregnancy test rather than within seven days of first seeing their doctor.

Accutane is considered the biggest breakthrough in acne drug therapy in the past two decades and is the only drug with the potential to clear acne permanently after once course of treatment, which is usually five months. Accutane should be reserved for cases of severe recalcitrant nodular acne, the type of acne resistant to standard acne treatment, including oral antibiotics, and is characterized by many nodules or cysts-inflammatory lesions filled with pus and lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.

Since the FDA approved Accutane in 1982, nearly 5 million people in the U.S. and 12 million worldwide have been treated with it. Half the patients taking the are females, most of childbearing age. Accutane is known to be teratogenic, or able to cause birth defects, and is designated Category X, meaning it must be avoided under all circumstances during pregnancy. Nursing mothers also should not use Accutane. Birth defect risk among pregnant women is extremely high-25 to 35 percent-and include hydrocephaly (enlargement of the brain's fluid-filled spaces) and microcephaly (small head), heart defects, facial deformities such as cleft lip and missing ears, and mental retardation. This does not account for other defects not detectable at birth, such as learning disabilities. Also, patients may develop serious problems affecting organs such as the liver, intestines, eyes, ears, and skeletal system. Some patients have developed serious psychiatric problems, including depression; some have developed suicidal behavior and others have succeeded in their suicide attempts.

Accutane Could Cause Depression by Lowering Serotonin Levels

Tue, 13 Nov 2007 00:00:00 -0800

Accutane, a controversial drug used to treat severe acne, has long been associated with higher rates of depression among users. Now, researchers in Britain and the United States believe they have discovered the cause for this Accutane side effect. It seems that Accutane decreases serotonin levels in the brain, which in turn can lead to depression and even aggressive behavior.

Introduced in 1982, Accutane has been the subject of controversy for years. It has been associated with psychiatric problems, and has been linked to 266 cases of suicide in the United States. In addition to its connection with depression, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. Accutane has also been linked to problems of the liver, kidneys, digestive tract, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.

Earlier this year, scientists from Bath University in conjunction with the University of Texas in Austin conducted experiments on mice that showed that Accutane made the mice behave in ways comparable to depression in humans. Now, in an article published in the journal Experimental Biology and Medicine, those same scientists have revealed a potential mechanism that might link Accutane to reported cases of depression in some patients taking the medication. Using cells cultured in a laboratory, the researchers monitored the effect of Accutane on the chemistry of the cells that produce serotonin. The researchers now say that Accutane could be disrupting the process by which serotonin relays signals between neurons in the brain.

Serotonin is a hormone found in the pineal gland, blood platelets, the digestive tract, and the brain. Serotonin acts both as a chemical messenger that transmits nerve signals between nerve cells and that causes blood vessels to narrow. Changes in the serotonin levels in the brain can alter the mood, and low levels of serotonin have been linked to depression, as well as bipolar disorder and anxiety disorders.

The link between low serotonin levels and Accutane use is further confirmation that this drug causes psychiatric problems – something that has been known for quite a long time. In fact, the manufacture of Accutane, Roche AG, knew about these problems long before they were made public. A 2004 USA Today article reported that, in the mid-1990s, contrary to advice from its own doctors, Roche executives chose not to issue stronger warnings about Accutane’s depression risks. According to the article, Roche decided against the warnings after its marketing department expressed concern that doing so would hurt sales. At the time, Accutane was one of Roche’s top-selling medications, bringing in more than $1.2 million every year. In 1999, in the face of mounting evidence, the Food & Drug Administration finally required Roche to include a suicide warning on the Accutane package insert.

Accutane Label, iPledge Monitoring Program Changes Approved by FDA

Thu, 18 Oct 2007 00:00:00 -0700

The label for Accutane will be changed in an effort to improve the effectiveness of the iPledge pregnancy risk management program. The changes were announced by the Food & Drug Administration (FDA) earlier this month, and are based on recommendations made by an outside advisory panel over the summer. The label changes will apply to both Accutane, the name brand of isotretinoin, and to its generic counterparts.

Accutane and other forms of isotretinoin are used to treat severe acne, but they carry an extremely high risk of causing birth defects if a female patient is pregnant. For that reason, pregnant women are barred from using Accutane. The iPledge program was established in 2006 as a way to make sure that women taking accutane were not or did not become pregnant while using it. It required, among other things, that female patients submit to regular pregnancy tests and that they sign a promise to use contraceptives while taking Accutane.

But earlier this summer, a report was released showing that the FDA’s iPledge program was not entirely successful in keeping the drug from expectant mothers. In its first year, 122 women in the iPledge program were either pregnant when they started taking Accutane, or became pregnant while doing so. In some cases, the pregnancy test the women took prior to getting their Accutane prescription had a false-negative reading. In two cases, the women actually convinced their doctor to enter fake test results into the iPledge database. But most of the pregnancies were the result of contraceptive failure.

Many dermatologists also complained that the iPledge program was too complicated and unwieldy. This summer, an FDA advisory panel agreed with this assessment and recommended several changes to the iPledge program. For example, it recommended doing away with rules that said a woman must have a pregnancy test and fill her Accutane prescription within seven days of seeing her doctor. The panel recommended changing the rule to allow such a patient to get an Accutane prescription from her doctor within seven days of the test. Another recommendation was to allow a patient to have a second pregnancy test and receive a new prescription if she misses the seven day window. The FDA has decided to follow the advisory panel’s recommendation, and the new Accutane labeling will reflect these changes to the iPledge program.

Many of the changes were originally proposed by Roche AG, the maker of Accutane, and the other isotretinoin manufacturers. They say the modifications will improve the flexibility of the iPledge program, reduce interruptions in treatment and reduce the burden on patients, doctors and pharmacies.

FDA Accutane Panel Says to Loosen Restrictions, Despite Risk of Birth Defects

Fri, 03 Aug 2007 00:00:00 -0700

Despite the fact that Accutane and other isotretinoin-containing medicines are still being used by pregnant women, a Food and Drug Administration (FDA) advisory panel recommended loosening restrictions on the drugs. Accutane and other drugs in its class are used to treat acne. However, these medications pose a substantial risk of birth defects if taken by pregnant women.

Just days before the FDA advisory panel made its recommendations, a report was released showing that the FDA’s iPledge program was not entirely successful in keeping the drug from expectant mothers. The iPledge program, which became mandatory last year, requires that all patients sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must sign a pledge promising to use birth control while taking Accutane. In its first year, 122 women in the iPledge program were either pregnant when they started taking Accutane, or became pregnant while doing so. In some cases, the pregnancy test the women took prior to getting their Accutane prescription had a false-negative reading. In two cases, the women actually convinced their doctor to enter fake test results into the iPledge database. But most of the pregnancies were the result of contraceptive failure.

The FDA advisory panel wants to lift some of the restrictions of the iPledge program. For example, under current rules a woman must have a pregnancy test and fill her Accutane prescription within seven days of seeing her doctor. The panel wants to change the rule so that a patient can get an Accutane prescription within seven days of the test. Another rule change would allow a patient to have a second pregnancy test and receive a new prescription if she misses the seven day window. Currently, if a patient does miss that window, they must wait 23 days to take another test before getting Accutane.

The panel also suggested that the iPledge program should encourage Accutane users who do become pregnant to provide the FDA follow-up information on their pregnancies. Of the 122 women who became pregnant, only about a dozen supplied such information. The FDA panel criticized a questionnaire the iPledge program used for this purpose, saying that it had a “punitive” tone. For instance, the panel did not like the way questions about educational background followed those about contraceptive failure. According to an Associated Press report, one panel member said that the questions implied that a woman became pregnant because she was “stupid”.

The FDA panel said that the proposed rule changes are minor, and should not affect pregnancy rates among Accutane users. They maintained that the alterations would make compliance easier.

In addition to birth defects, Accutane has been linked to Inflammatory Bowel Disorder, as well as psychiatric problems. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems. Accutane and the other drugs in its class are only supposed to be used for the most severe types of acne. However, it has long been known that doctors prescribe these medications to patients with milder acne.

Accutane Still Reaching Pregnant Women Despite Much Touted iPledge Program

Wed, 01 Aug 2007 00:00:00 -0700

Women taking Accutane are still becoming pregnant, despite a program that is supposed to keep the drug away from expectant mothers. The program, known as iPledge, was designed to insure that pregnant women would not take Accutane and other medications containing isotretinoin, an agent known to cause birth defects.

The iPledge program was initiated by the Food and Drug Administration (FDA) and became mandatory last year. All patients using isotretinoin must enroll in iPledge, as well as doctors who prescribe the drug and the pharmacies that sell it. The program requires patients to sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must sign a pledge promising to use birth control while taking Accutane.

When iPledge was first introduced, the FDA hailed the program as an effective vehicle for preventing the birth defects associated with Accutane. But a report issued by the FDA and the companies that manufacture isotretinoin-containing drugs released earlier this week says that the program is falling short. In the first year of iPledge, 122 pregnancies were reported among female participants. Of those, 78 were taking the drug when they became pregnant, and 10 were already pregnant when they were first prescribed the drug. Incredibly, two of those women are known to have had their doctors falsify their pregnancy tests. Most of the pregnancies that occurred after the woman started taking isotretinoin came about because the patients were not diligent about using contraceptives.

Accutane and other isotretinoin-containing medications are never safe during pregnancy. Even if an expectant mother takes the drug in small doses over a short period of time, her baby has a greater chance of suffering severe brain and heart defects, mental retardation and other problems. And the risk continues for about thirty days after a woman stops using Accutane. In addition to birth defects, Accutane has been associated with myriad other serious side effects. It has been linked to Inflammatory Bowel Disorder, as well as psychiatric problems. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems. Accutane and the other drugs in its class are only supposed to be used for the most severe types of acne. However, it has long been known that doctors prescribe these medications to patients with milder acne.

The March of Dimes, an organization dedicated to preventing birth defects, said on its website that it is evaluating the report and will carefully review any proposed changes to the iPledge program. The FDA has scheduled a meeting of its Dermatologic and Ophthalmic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee for later today to discuss the iPledge program’s shortcomings.

Accutane Maker Roche AG Ordered to Pay $2.62 Million to Patient Who Developed Inflammatory Bowel Syndrome After Using Drug

Wed, 13 Jun 2007 00:00:00 -0700

A New Jersey jury has awarded $2.62 million in damages to a patient who needed to have his colon removed after taking the drug Accutane. The case was the first of more than 400 suits pending against Roche Holdings AG, the manufacturer of Accutane acne medication. The verdict, issued on May 29, could be ominous news for Roche, as many legal analysts believe it portends more findings against the company.

Andrew McCarrell, the plaintiff in the case, developed Inflammatory Bowel Disease (IBD) after taking Accutane for four months in 1995. In addition to having his colon removed, McCarrel also had most of his rectum removed and had to wear a colostomy bag for years. He recently had surgery that rid him of the colostomy bag, but the 36-year-old software manager testified that he still suffers from severe, chronic diarrhea.

The jury agreed with McCarrell’s lawyers that the Accutane label did not provide sufficient warning about the drug’s IBD risk. In addition to the $2.62 million, the jury also awarded McCarrel $119,000 to cover medical expenses.

Introduced in 1982, Accutane has been the subject of controversy for years. In addition to IBD, the drug has been associated with myriad other serious side effects. It first garnered attention in the late eighties for causing severe birth defects. It has also been known to cause psychiatric problems, and has been linked to 266 cases of suicide in the United States. Accutane has also been associated with problems of the liver, kidneys, central nervous system, and pancreas, as well as the cardiovascular, musculoskeletal and auto-immune systems.

A 2004 USA Today article reported that, in the mid-1990s, contrary to advice from its own doctors, Roche executives chose not to issue stronger warnings about Accutane’s depression risks. According to the article, Roche decided against the warnings after its marketing department expressed concern that doing so would hurt sales. At the time, Accutane was one of Roche’s top-selling medications, bringing in more than $1.2 million every year.

In 1997, in the face of mounting evidence, the FDA finally required Roche to include a suicide warning on the Accutane package insert. Then in 2006, the FDA began the iPledge registry program. This program requires patients to sign a document informing them of the drug’s risks. Patients must also agree not to share their medication with anyone else, and to make follow up visits with their doctors. The program has special requirements for women of childbearing age, including the requirement that they submit to regular pregnancy tests at their doctor’s office. The prescribing physician is then required to enter the results of the tests into the iPledge database. Women also must to sign a pledge that they would use birth control while taking Accutane. Despite these precautions, many consumer advocacy organizations have called for Accutane to be removed from the market, contending that its risks far outweigh its benefits.

Research shows link between acne treatment and depression

Tue, 19 Sep 2006 00:00:00 -0700

The first scientific evidence of a link between a drug for severe acne and depression was unveiled yesterday, following years of denials by the manufacturer that the prescription medicine could be in any way responsible for suicides.

Roaccutane has been linked to more than 100 suicides and attempted suicides worldwide. In April last year, an inquest heard that Jason Spiller, 16, killed himself after starting the drug. The coroner said, as have other coroners, that there was no clear evidence of a relationship between Roaccutane and depression. The previous year, David Roberts, a 20-year-old, killed himself while on the drug. Seumas Todd, 20, son of the actor Richard Todd, killed himself in 1997 while taking Roaccutane.

Roche, the manufacturer, maintains that the drug is not the problem, pointing out that the underlying condition could be to blame. The drug's information leaflet has, since 1998, warned patients may be at risk of becoming suicidal, at the request of the Medicines and Healthcare Products Regulatory Authority (MHRA).

But yesterday, scientists from Bath University, with the University of Texas, revealed that they have conducted experiments on mice which show that the drug makes them behave in a way that is recognised as the result of depression.

Sarah Bailey from the department of pharmacy and pharmacology at Bath, said that more research would be needed before anybody could be sure the same effect occurs in humans on the drug.

"Establishing a link between the active molecules within the drug and a change in depression-related behaviour, albeit in mice, is an important step forward in our understanding of the effects of this drug," she said. "To date the only evidence for any link with patients has come from individual case reports and such patient data is complicated by the psychosocial effects of having severe acne."

The researchers injected mice with Roaccutane for six weeks to achieve similar levels in the blood to those of humans taking the tablets. Then they put them through tests recognised as models for measuring the effects of depression in rodents. One was a "forced swim" test, where the animals were placed in water. The time they spent attempting to climb out was compared with the behaviour of mice that had not been given the drug.

The mice on Roaccutane spent longer immobile, without attempting to escape - a recognised sign of depressed behaviour - the researchers report in the journal Neuropsychopharmacology.

The father of Liam Grant, 19, from Dublin, is suing Roche in an attempt to prove Roaccutane caused his death. Mr Grant - also called Liam - has spent £340,000 on studies, including one published by the American Academy of Psychiatry, which scanned the brains of 15 people on Roaccutane and 15 on other acne medication. They found changes in part of the brain associated with depression. Mr Grant has been offered, without any admission of liability, a settlement of all his costs and the maximum compensation payable in the event of winning his case by Roche around £800,000 - but he has refused to take it. Roche said it has not had time to examine the new results.

Backstory

Roaccutane is intended for patients over the age of 12 with severe acne and is sometimes prescribed when antibiotics have failed. It is known to damage the foetus, so women of an age to become pregnant can only have a month's supply at a time and may have to undergo a pregnancy test. Concerns over links to depression and suicide have been around for some years. The Medicines and Healthcare Products Regulatory Authority has received 1,588 reports of suspected adverse events experienced by people taking the drug between licensing in 1983 and September this year. In 38 cases, people died and 25 of those were suicide. The MHRA says the safety of roaccutane is under constant scrutiny. In June last year an expert working group recommended patients be monitored for signs of depression.

Accutane heart, liver risks higher than expected

Mon, 21 Aug 2006 00:00:00 -0700

Accutane, the powerful acne drug already known to cause birth defects, seems to raise the risk for potential heart and liver problems more than doctors had expected, according to a new study.

The findings came from lab tests on 13,772 patients taking the popular acne drug and underscore the need to closely monitor people taking isotretinoin, which is sold as Accutane and in three generic versions. Abnormal results for cholesterol and liver function were more common than expected.

While those conditions can lead to problems over the long term, abnormal lab tests don’t necessarily mean patients will develop heart or liver problems, said study co-author Dr. Lee Zane of the University of California, San Francisco.

“An elevation in cholesterol doesn’t guarantee a heart attack. A high level of liver enzymes doesn’t mean cirrhosis of the liver,” Zane said.

Further studies would be needed to determine any long-term health effects, he said, but in the current study, most patients’ abnormal lab tests returned to normal when they quit taking the drug.

Patients usually take it for less than a year at a cost of $10 to $15 per daily pill. It’s considered one of the most effective treatments for the severest acne.

On March 1, the U.S. Food and Drug Administration began requiring patients and doctors to register their use of the drug, a program intended to stop birth defects.

Isotretinoin can cause brain and heart defects in infants if a woman takes it during or immediately before pregnancy. More than 71,000 patients have registered in the FDA’s registry. Women who take it must have pregnancy tests and use birth control or abstain from sex.

Most dermatologists already knew the drug also could increase levels of cholesterol, liver enzymes and blood fats called triglycerides that can raise the risk of heart disease. But the new study found higher than expected percentages of patients developing these abnormal lab results.

Among patients with normal lab tests before they started taking the drug, 44 percent developed high levels of triglycerides. The package insert, by contrast, cites high triglycerides in 25 percent of patients.

Thirty-one percent of healthy patients in the study developed high cholesterol levels and 11 percent developed abnormal liver tests.

The patients ranged in age from 13 to 50 and were treated between March 1995 and September 2002. They were all members of the Kaiser Permanente health plan in northern California. The findings were published in Monday’s Archives of Dermatology.

Some patients in the study had more lab tests than others during their treatment with the acne drug, but, for their analysis, the researchers used only the most abnormal test result for each different test each patient had.

The researchers also looked at lab tests for levels of white blood cells, hemoglobin and platelets. They found these were rarely abnormal.

The study won’t change medical practice because dermatologists already carefully test patients taking Accutane, said Dr. John Strauss, professor emeritus at the University of Iowa College of Medicine. Strauss is a former consultant for Roche Laboratories Inc., the maker of Accutane, he said.

Roche representatives did not reply to an e-mail seeking comment on the study.

The drug is sometimes the only way to treat severely disfiguring acne, Strauss said. Some risk could be acceptable for patients whose acne is severe, he said.

“I’ve got patients who have said to me, ’You’ve saved my life with this drug,”’ Strauss said.

Health Canada probes Accutane side effects

Mon, 17 Apr 2006 00:00:00 -0700

Health Canada is investigating reports of strokes and heart attacks in people taking Accutane, the controversial acne drug that causes birth defects and has been linked with psychiatric problems.

Twenty-nine cases of patients who developed a vascular disorder after taking isotretinoin, the generic name for Accutane, have been reported since the drug was approved in Canada in 1983.

Eleven involved strokes, blood clots or a heart attack, none of which are labelled as possible reactions in the drug's prescribing information. The patients ranged in age from 15 to 48.

One 18-year-old with no known risk factors suffered a stroke two months after starting the drug.

"Health-care professionals are encouraged to report any cases of myocardial infarction, cerebrovascular and thromboembolic disorders suspected of being associated with isotretinoin," a new Health Canada report on adverse drug reactions says.

Canadian retail pharmacies filled 224,515 prescriptions for Accutane last year, worth $33.8 million, according to IMS Health Canada. Isotretinoin's use is expected to grow as cheaper generic versions reach the market.

A spokesperson for Health Canada stressed there is no evidence Accutane caused the rare reports of stroke and blood clots in users. They're based on suspicions only and could be due to some underlying illness. Some of the patients had risk factors for stroke, such as high blood pressure or obesity.

"This information at this point is strictly observational, they are only suspected to be associated with Accutane. Causal relationships have not been determined," Health Canada spokesperson Chris Williams said.

The cases were published in the latest issue of the Canadian Adverse Reaction Newsletter "to stimulate reporting to see if something needs to be done," Williams said. "That's why we're putting it out."

It's been estimated that as few as one per cent of suspected reactions are ever reported under Canada's voluntary reporting system,

Accutane Registry to Begin on March 1 as Planned – FDA Refuses to Delay Program Any Further

Mon, 27 Feb 2006 00:00:00 -0800

Although the American Academy of Dermatology and other critics of the iPledge registry (designed to prevent pregnant women from using the acne drug Accutane) mounted a last-minute campaign to further postpone the system from going into effect, the FDA has decided to adhere to the March 1 starting date.

After only a few months of trial use of the registry system, the nation’s leading dermatology association told an FDA advisory panel that the program was a “disaster.” The program was originally scheduled to begin on November 1, 2005.

According to Academy member Dr. Diane M. Thiboutot: “Pharmacies, prescribers and patients are confused and frustrated." There have been hundreds of complaints from dermatologists prompting the association to request that the FDA delay the system's mandatory starting date of March 1 by at least two months.

The agency had indicated it would rule on the postponement request within a week. Supporters of the registry system maintain that the problems being encountered are being overblown.

The iPledge system was an effort to keep Accutane from being pulled from the market. The four manufacturers of the drug fully realized that, without reducing the number of miscarriages, abortions, and birth defects, Accutane’s days were numbered.

As we previously reported, the strange thing about Accutane is that it was never intended to treat the huge number of patients for whom it is being prescribed. The severe, disfiguring type of acne the drug was designed for only affects some 6,000 women of childbearing age in the U.S. Doctor’s, however, may prescribe the drug as they choose. Thus, in 2002-2003, some 156,800 women of childbearing age were prescribed the drug, or 2,600% more than actually fit the profile for which the drug is intended.

As a result of what critics consider the over-prescribing of the drug, some 100,000 prescriptions each month are filled by women; many of these women become pregnant while taking the drug. The over-prescribing has also had the effect of making Accutane a big moneymaker for it s manufacturers.

The problems with the system appear to be that it is inconvenient, cumbersome, and difficult to manage, while also suffering from slow telephone support when a doctor needs assistance. As a result, doctors are becoming discouraged and may simply stop prescribing the drug.

The FDA says it is aware of the problems and Covance, the company that operates the system, claims to be fixing them as quickly as possible. The process, however, often takes weeks to complete.

The strict regulations imposed by the iPledge system are seen as absolutely necessary by those who advocate tighter control of Accutane. Although over 27,000 people have signed up so far, there is a long way to go before all those who must sign up have registered. As reported in the New York Times, Dr. Peter A. Gross, the panel's chairman and chairman of the department of internal medicine at Hackensack University Medical Center in New Jersey, dismissed the complaints. "You get no sympathy from me. If it takes a little more time, tough."

In addition, Dr. Sidney Wolfe, director of health research at Public Citizen stated: "There is this never-ending whimpering coming from many dermatologists that someone is cramping their style and making it more difficult to prescribe something. The reason there are all these failed efforts to limit pregnancies is that dermatologists are prescribing Accutane to way too many people."

According to the New York Times article: “Representative Bart Stupak, a Democrat from Michigan who has long advocated that Accutane be withdrawn from the market, said complaints about the new system were exaggerated. Mr. Stupak sent a letter to the committee insisting that there be no delays in putting the new control system in place.”

“‘But I expect that the F.D.A. will once again cop out and not do the right thing’ and agree to a delay, Mr. Stupak said in an interview.” Apparently, however, the FDA has decided that, notwithstanding the procedural difficulties, the program should be launched. While critics of the drug are pleased by the decision, they remain adamant that Accutane (and its equivalents) should be removed from the market entirely.

For years, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.

Both Accutane and its generic versions, which include the active ingredient known as isotretodnin, are known to cause birth defects when taken by pregnant women.

The FDA and the drug’s manufacturer, Hoffman-LaRoche, already provide information about this adverse health risk in the labeling and packet information for Accutane.

Unfortunately, research continues to indicate that despite all the warnings, some women continue to use Accutane while pregnant. This has been an ongoing problem for 23 years during which time the FDA has been unsuccessful in some 40 initiatives to prevent women from taking the drug while pregnant.

While most of the 2,000-plus reported pregnancies during Accutane use have resulted in abortions or miscarriages, there have been over 160 babies born with isotretodnin-related birth defects. It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies for many years.

A report appearing online in Birth Defect Research in 2005 found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn’t remember hearing the guidelines relating to Accutane usage and pregnancy. (A teratogen is a substance that causes birth defects.)

Surprisingly, eight of the 34 women said that they didn’t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.

In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane that will become mandatory on March 1.

Previously, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.

The new program, called “iPLEDGE,” requires that all women of childbearing age take the following steps:

•    Sign an informed consent form in their doctor’s office;
•    Personally register with iPLEDGE;
•    Take two negative pregnancy tests in a doctor’s office within seven days of beginning treatment;
•    Agree to use two forms of birth control while taking the drug;
•    And get another negative pregnancy test in a doctor’s office within one week of requesting a refill.

Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.

Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. Doctors must make sure that patients are aware of the drug’s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.

Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.

Information about the iPLEDGE program was also made available at (866) 495-0654, or online at www.ipledgeprogram.com.

Since its approval in 1982, Accutane has been linked to serious potential side-effects including:
•    birth defects when taken by pregnant women
•    psychological problems including possible suicide
•    neurological problems
•    stomach, bone and muscle problems
•    hearing and vision problems
•    problems with fats and cholesterol in the blood
•    ulcerative colitis
•    Crohn’s disease
•    inflammatory bowel disorder
•    rectal bleeding
•    abdominal pain
•    central nervous system injuries
•    bone and muscle loss
•    cardiovascular injuries
•    liver and kidney damage
•    pancreatitis
•    immune system disorder
•    lupus
•    thyroid disorders
•    various allergic reactions
•    Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.

In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.”

This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.

By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.

Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.

The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.

As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.

In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.

Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.

Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.

In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.

The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain, an area known to mediate symptoms of depression.

The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.

The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauded the recent efforts of the FDA. Still, the organization had its doubts about the new registry. For one thing, the registry does not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.

There was also concern that people might get confused with the many generic forms of isotretodnin and may still end up taking Accutane and putting themselves at risk without even knowing it.

In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:

•    Feelings of sadness or crying spells
•    Loss of interest in activities once enjoyed
•    Sleeping too much or having trouble sleeping
•    Having increased irritability, anger, or aggressively (i.e. temper outbursts, thoughts of violence)
•    Change in appetite or body weight
•    Trouble concentrating
•    Withdrawal from family or friends
•    Loss of energy
•    Feelings of worthlessness or inappropriate guilt
•    Thoughts of self-harm or suicide

In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.

Currently, litigation involving the following injuries is either in progress or being considered in a number of states:

•    Inflammatory Bowel Disease
•    Premature Closure of Growth Plates
•    Birth Defects
•    Ulcerative Colitis
•    Crohn's Disease
•    Inflammatory Bowel Syndrome
•    Rectal Bleeding
•    Abdominal Pain
•    Central Nervous System Injuries
•    Bone and Muscle Loss
•    Cardiovascular Injuries
•    Liver and Kidney Damage
•    Pancreatitis
•    Immune System Disorder
•    Lupus
•    Hearing and Vision Damage
•    Thyroid Disorders

Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.

The basis for the strong opposition to the drug was expressed best in the Public Citizen publication Worst Pills Best Pills (April 2004 Newsletter. The more compelling sections of that article are as follow:

“Public Citizen’s Health Research Group has been warning the FDA about the risks of birth defects and mental retardation for fetuses exposed to isotretinoin (ACCUTANE) for over 20 years. In 1983 we sent a petition recommending patient package inserts and a black box warning describing the risks of birth defects and life-threatening side effects of the drug. The next year we sent a letter advocating improved pregnancy surveillance and lower dosing regimens. In 1988 we described isotretinoin as an imminent public health hazard to an FDA Advisory Committee and we urged the FDA to remove it from the market unless tight restrictions were implemented and proved effective.

The following year we testified and again urged the FDA to remove isotretinoin from the market unless our previously proposed restrictions were immediately adopted…Then, in 2000 we testified and recommended a Patient Medication Guide and again advised removal from the market unless the restrictions were implemented and shown to be effective.

In 1989, the CDC testified before an FDA Advisory Committee, stating that, ‘[t]he birth of babies with defects caused by fetal exposure to Accutane is unnecessary,’ and the ‘...FDA decision to allow the marketing of Accutane [is] a failed regulatory experiment.’ They also declared that a ‘...decision to depend on better contraception alone, without active intervention to reduce the number of users, is a decision to leave the number of affected babies at an unacceptably high level.’ They suggested that ‘[p]erhaps a formal IND would be a suitable mechanism...to reduce the frequency of Accutane embryopathy.’ This echoes Public Citizen’s recommendation to remove Accutane from the market and reintroduce it only under strict Investigational New Drug (IND) restrictions.

Since there is currently no reporting requirement for pregnancies exposed to isotretinoin, the actual numbers of affected pregnancies are unknown. There is information from surveys and spontaneous reporting, however, and according to data presented at the 2000 FDA Advisory Committee meeting, there have been 1,995 pregnancies exposed to Accutane between 1982 and 2000. The known outcomes of these pregnancies included 1,214 elective abortions, 383 live births, and 162 infants with birth defects. During the first year of S.M.A.R.T., the System to Manage Accutane Related Teratogenicity, there were 156,800 ‘unique’ women who were given the drug, and the pregnancy rate was estimated at 0.35%. We can therefore calculate that there would be 548 total pregnancies, which is 4.6 times higher than the 120 pregnancies spontaneously reported. Of 61 pregnancies with known outcomes, 48/61 or 78.7% resulted in elective abortions.

Applied to the 548 estimated pregnancies, there would have been 431 elective abortions in that year. Of 61 pregnancies with known outcomes, 7/61 or 11.5% resulted in deliveries. Based on the 548 estimated pregnancies, there would have been 63 deliveries. Using estimates of 25% birth defects and 50% mental retardation, this would result in 16 infants with birth defects and 31 with mental retardation.

Proposals of S.M.A.R.T. and the new Roche, the drug’s manufacturer, have failed to seriously address two major issues. The first is the need for at least a 95% reduction in prescribing. The CDC estimated in 1989 that there were no more than 4,000 women of child-bearing age with severe cystic acne. Adjusting for population growth, this number may now be 6,000. Given that there were 156,800 ‘unique’ women of child-bearing age who got the drug in 2002-2003, this represents a twenty-six fold excess in prescribing over the number of on-label prescriptions. The second problem is the need for mandatory pregnancy test results (not just assurance) before starting therapy and monthly while on therapy as a prerequisite for getting every prescription filled.

We therefore insist on the withdrawal of isotretinoin from the market. Twenty years of failed voluntary and, more recently, mandatory restrictions have led to a total of more pregnancy exposures because the total number of prescriptions has increased. As we recommended in 1988 and the CDC suggested the next year, a ban on marketing with subsequent availability only under a tightly controlled investigational new drug application (IND) procedure is the only feasible way to significantly reduce prescriptions and pregnancy exposures.

The S.M.A.R.T program is clearly a failure. Without these proposed IND restrictions, this administration and this advisory committee will continue to put its imprimatur on the reckless use of a drug that each year causes the need for hundreds of abortions and many seriously deformed infants with birth defects and/or mental retardation. It is time to end the more than twenty years of voluntary restrictions that have failed to reduce its prescribing for more than ten times as many women as would be using the drug if it were limited to the approved indications.”

Clearly, the iPledge program is the last real hope of countering the devastating effects of Accutane associated with pregnant women and their unborn fetuses. Beyond that, many experts, including doctors within the FDA itself, continue to call for the complete withdrawal of the drug based upon its extremely serious side-effects and potential adverse reactions in all patients and not just pregnant women.

Accutane Registry to Begin Next Week

Wed, 22 Feb 2006 00:00:00 -0800

Dermatologists are renewing their concerns that efforts to prevent pregnant women from using a drug that can cause birth defects may also keep the drug from patients who need it for severe acne.

The iPledge program to register women of childbearing age who use the drug Accutane and its generic versions requiring them to have pregnancy tests before getting a prescription is scheduled to take effect March 1.

The American Academy of Dermatology had urged the Food and Drug Administration to postpone the start of iPledge, but said Tuesday the FDA had advised it that the program will begin as planned.

The FDA had delayed implementation from last November to March 1, but did not immediately confirm the decision not to postpone it further.

The program focuses on the drug isotretinoin, best known as Accutane but also sold generically as Amnesteem, Claravis and Sotret.

AAD President Dr. Clay J. Cockerell said in a statement he was disappointed in the decision not to delay iPledge, adding that "it is now the duty of the FDA to guarantee that the flaws, inconsistencies and confusion" in the program are resolved.

Dr. Diane M. Thiboutot of the Penn State University College of Medicine in Hershey, Pa., said attempts to use the system have shown it to be complex and that it may prevent patients from getting medicine for forms of acne that can cause severe scarring.

The system requires patients, physicians and pharmacies to register via computer and the patients must fill their prescription within a seven-day window. However, she said, some didn't get passwords in time, resulting in their being prevented from getting the drug for 23 days. She said other problems also occurred.

This is the only drug that can prevent severe scarring and "we're really concerned that this system may mark the beginning of an inability of patients who need the medication to get medication," Thiboutot said.

If a pregnant woman uses the drug, or if a woman becomes pregnant within a month of taking it, her baby runs a significant risk of brain and heart defects, as well as mental retardation.

While the manufacturers of the four drugs have operated similar but smaller registry programs, FDA estimates that 100 to 140 pregnancies a year still occur in the United States in women on the drug. About 100,000 Americans are prescribed the drug monthly.

Since Accutane sales began in 1982, the FDA has received reports of more than 2,000 pregnancies among users. Most ended in abortion or miscarriage, but the FDA counts more than 160 babies born with drug-caused defects.

Under iPledge, women of childbearing age must undergo two tests to ensure they're not pregnant before the initial prescription, and monthly pregnancy testing before each refill. Home pregnancy tests won't do. The doctor must enter the pregnancy test results into the iPledge system, and the woman must buy her pills within seven days.

These women also must agree to use two forms of birth control while using the drug, and must self-register on iPledge in addition to the doctor's initial registration to report that they're doing so.

Congressman's Family Uses Clout to Raise Accutane Awareness

Fri, 03 Feb 2006 00:00:00 -0800

The possible dangerous side effects of Accutane have been in the news for some time. Doctors say the drug prescribed for severe acne can cause depression and even suicidal thoughts.

A Menasha couple is warning parents not to agree to Accutane prescriptions for their children. Their son, Justin Zimmer, took his life last month, less than four weeks after he began using the drug (see related story), and they say there were never any warning signs.

U.S. Congressman Bart Stupak of Menominee, Michigan, and his family went through a similar situation almost six years ago. Stupak's son was 17 and using Accutane when he killed himself.

B.J. Stupak was an all-American boy in high school. Besides having tons of friends, he was active in football, baseball, and student council. On the morning after his junior prom in May, 2000, he did something that nobody saw coming.

"He went upstairs. I had kept a handgun in my nightstand, which I kept for security, safety reasons, and he somehow took the handgun and shot himself," his mother, Laurie Stupak, recalled.

His devastated family could not find an answer to the question why. "We had never gotten any type of warning whatsoever."

His mother was in search of answers so she did some research on the Internet.

"Typed in the word 'Accutane' and that's when I found links between Accutane and depression and suicide."

The family says they were never warned of that information. Since then, the Stupaks have utilized their political power to get the word out.

"Our ultimate goal is to prevent tragedies occurring for other families," she said.

The fight is paying off somewhat. Since August 2005, the drug's packaged label information has read "Accutane may cause depression and rarely suicide."

The Food and Drug Administration's Web site says it is continuously "assessing reports of suicide associated with the drug's use."

Stupak says the expensive drug, which is meant for severe acne cases, is still overprescribed while its dangerous side effects are underpublicized.

"It makes us feel frustrated to know that we work so hard but yet there are other cases out there where people aren't getting the necessary info."

Information the Stupaks say would have prevented them from investing in this drug in the first place.

Acne Drug Blamed for Son's Suicide

Thu, 02 Feb 2006 00:00:00 -0800

A Menasha couple blames the acne drug Accutane for there son's suicide.

Warren and Wendy Zimmer say there is no other reason their son would suddenly take his own life. By all accounts, Justin Zimmer was a good kid with a great future ahead of him. He was an A student, class president, and very good athlete in three sports.

But he had complexion issues, and on December 19, his doctor prescribed Accutane. Less than a month later, on January 15, Justin took his own life.

His parents put the blame squarely on the side effects of Accutane, which include depression.

"We were thinking that it would be something like a progressive thing that you would notice a change," Warren Zimmer said.

"He promised us that if he felt any differently that he would definitely talk to us. We were comfortable with that," said Justin's mother.

Justin's parents say neither they nor any of his friends detected any signs of depression or suicidal tendencies.

"He had so many things to look forward to. His birthday is tomorrow. He was supposed to get his drivers license tomorrow," Wendy Zimmer said. "He was looking forward to that!"

The Zimmers say the medical community is suddenly silent about Accutane. The Zimmers, however, have a message for anyone about to use Accutane, even if it was clearing their son's complexion.

"Don't do it," they said. "It's not worth it."

"Justin was a beautiful person inside. It didn't matter what his face looked like."

Researchers Find Some Women Still Unaware of Serious Birth Defects Linked to Accutane Use during Pregnancy

Sun, 16 Oct 2005 00:00:00 -0700

For some time now, it has been well-publicized that Accutane, a drug used to treat severe acne, can pose a significant risk of birth defects if taken during pregnancy.

Both Accutane and its generic versions, which include the active ingredient known as Isotretonin, are known to cause birth defects when taken by pregnant women.

The FDA and the drug’s manufacturer, Hoffman-LaRoche, now provide information about this adverse health risk in the labeling and packet information for Accutane.

New information, however, indicates, that despite all the warnings, some women continue to use Accutane while pregnant.

A recent report appearing online in Birth Defect Research found that 34 women called a hotline run by the Organization of Teratology Information Services between April 2002 and September 2004 claiming they didn’t remember hearing the guidelines relating to Acctuane usage and pregnancy. (A teratogen is a substance that causes birth defects.)

Surprisingly, eight of the 34 women said that they didn’t recall being counseled about birth control prior to taking Accutane, and 25 said that they had not taken a second pregnancy test before taking the drug.

In light of these continued problems connected to education about the drug, the FDA introduced a new program with an entirely new set of rules for Accutane.

Up until recently, women who wished to begin treatment with Accutane had to get birth control counseling and have two negative pregnancy tests prior to beginning treatment with the drug.

The new program, called “iPLEDGE,” requires that all women of childbearing age take the following steps:

• Sign an informed consent form in their doctor’s office;
• Personally register with iPLEDGE;
• Take two negative pregnancy tests in a doctor’s office within seven days of beginning treatment;
• Agree to use two forms of birth control while taking the drug;
• And get another negative pregnancy test in a doctor’s office within one week of requesting a refill.

Men are also asked to sign an informed consent form to indicate that they too are aware of the risks but they do not have to personally register with iPLEDGE.

Doctors, pharmacies, and wholesalers are required to register with iPLEDGE. Doctors must make sure that patients are aware of the drug’s risks before they sign a consent form and begin the procedures to ensure safety in relation to Accutane usage.

Pharmacies must make sure that they log onto iPLEDGE before filling a prescription for Accutane to make sure that the patient has taken the necessary safety steps. Finally, wholesalers must agree to only supply Accutane to pharmacies that have registered with iPLEDGE.

For more information about iPLEDGE visit www.ipledgeprogram.com or call (866) 495-0654.

Since its approval in 1982, Accutane has been linked to serious potential side-effects including:

• birth defects when taken by pregnant women
• psychological problems including possible suicide
• neurological problems
• stomach, bone and muscle problems
• hearing and vision problems
• problems with fats and cholesterol in the blood
• ulcerative colitis
• Crohn’s disease
• inflammatory bowel disorder
• rectal bleeding
• abdominal pain
• central nervous system injuries
• bone and muscle loss
• cardiovascular injuries
• liver and kidney damage
• pancreatitis
• immune system disorder
• lupus
• thyroid disorders
• various allergic reactions
• Some minor side effects include dry
skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.

In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression.

Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.” This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.

By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.

Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.

The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.

As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.

In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.

Since Accutane’s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.

It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.

Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.
Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.

In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.

The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain an area known to mediate symptoms of depression.
The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.

The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauds the recent efforts of the FDA. Still, the organization has its doubts about the new registry.

For one thing, the registry will not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.

There is also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.

In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:

• Feelings of sadness or crying spells
• Loss of interest in activities once enjoyed
• Sleeping too much or having trouble sleeping
• Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
• Change in appetite or body weight
• Trouble concentrating
• Withdrawal from family or friends
• Loss of energy
• Feelings of worthlessness or inappropriate guilt
• Thoughts of self-harm or suicide
In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.

Currently, litigation involving the following injuries is either in progress or being considered in a number of states:

• Inflammatory Bowel Disease
• Premature Closure of Growth Plates
• Birth Defects
• Ulcerative Colitis
• Crohn's Disease
• Inflammatory Bowel Syndrome
• Rectal Bleeding
• Abdominal Pain
• Central Nervous System Injuries
• Bone and Muscle Loss
• Cardiovascular Injuries
• Liver and Kidney Damage
• Pancreatitis
• Immune System Disorder
• Lupus
• Hearing and Vision Damage
• Thyroid Disorders

Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.

Suicide Victim's Parents Push to Get Acne Drug Off Market

Wed, 28 Sep 2005 00:00:00 -0700

Belief that Accutane, a prescription acne medication with the chemical name isotretinoin, contributed to the suicide death of their son, Tammy and David Hestand of Bloomfield want to let as many people as possible know the drug's risks.

"It's my honest feeling that a minor, especially under 18, shouldn't be on this medication, because you can't watch them," Tammy said. "To give it to adults and let them take their life into their own hands is one thing, but to give it to someone 21 and under is another. I'm not sure people understand the true risks."

She said young people don't think they're going to die or that anything bad will happen to them. Knowing that if they tell the doctor they're having suicidal thoughts he'll take the "miracle drug" away, Tammy isn't sure they'd admit it.

"I think of it like heroin," she said. "I think people get addicted to it. Like I said my gosh his skin was beautiful. I think there's a fear factor of having it taken away.

"I can't see kids having responsibility enough to take it."

She said the majority of people taking isotretinoin are between the ages of 18 and 21.

"That freaks me out even more because the majority of those kids are off at college," Tammy said. "Who's watching them?"

Shelley Rosenstock, executive director of public affairs for Roche, the company that markets Accutane, said "the predominant number of Accutane patients is between 15 and 24 years of age."

Even when teens live at home, the Hestands said, it's hard to keep tabs on them 24/7 and, as Tammy pointed out, "Who knows what a teenager is thinking on a good day?"

She and David truly believe everything was fine on the Sunday morning Caleb took his life. She said the family simply noticed that no one had seen Caleb for a couple hours and began to look for him.

"He was fine, then two hours later he was gone," Tammy said.

"It looks like girls go into long-term depressive symptoms, but these high-achieving boys just go from zero to dead in a short time."

But Rosenstock said numerous scientific preclinical, clinical and epidemiological studies have failed to show a cause-and-effect relationship between Accutane and psychiatric events.

"The psychiatric events reported to the company and health authorities in association with Accutane treatment reflect the multiple risk factors in the population of adolescents and young adults," she said. "Suicide among young people occurs at such alarming levels that the U.S. Surgeon General, the Centers for Disease Control and Prevention, and a number of other federal and private groups have issued programs specifically directed at prevention of suicide in this age group.

"Mood disorders among teenagers are widespread and difficult to diagnose. In addition, there is extensive literature more than 50 studies documenting an association between acne and depression in adolescents."

The U.S. Food and Drug Administration has approved a risk management program called iPLEDGE to make sure females don't become pregnant while taking isotretinoin. But Tammy said her impression is that they're not looking at other side effects.

According to an FDA patient information sheet on isotretinoin, they assess reports of suicide or suicide attempts associated with the use of isotretinoin. The sheet also states: "All patients treated with isotretinoin should be observed closely for symptoms of depression or suicidal thoughts, such as sad mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating, or for mood disturbance, psychosis, or aggression. Patients should stop isotretinoin and they or their caregiver should contact their healthcare professional right away if the patient has any of the previously mentioned symptoms. Discontinuation of treatment may be insufficient and further evaluation may be necessary."

"It is important to note that the side effects reported in the product label are the result of reports from doctors and patients and do not establish that there is any cause-and-effect relationship between the drug and the particular condition," Rosenstock said.

"Over the years Roche has maintained constant vigilance regarding reports of mood disorders and suicides, and has discussed with them with FDA and other experts. As a result, the professional and patient information, including labeling, packaging, and prescriber and patient educational materials, have been enhanced through the years with comprehensive support materials, such as informed-consent forms and educational information. These changes have reflected prescriber and patient experience and even concerns about which there was no scientific validation, all for the cause of patient safety."

Still, Tammy said, people have been pulling together since 1999 to get isotretinoin off the market. She said a U.S. senator and a U.S. congressman each lost a child who was taking Accutane® to suicide. She said one of the legislators, in particular, has been lobbying for the drug to be taken off the market.

There have been a number of lawsuits, Tammy said, but it's a matter for the FDA, not the courts, to decide if isotretinoin will be removed from the market.

"VIOXX and others were voluntarily pulled," she said. "It's apparent with this drug they're not going to do anything willingly."

Talking to an Indiana trial lawyer with the Indiana Supreme Court, Tammy learned that if Roche loses Accutane, they'll lose half their profits. She said the company will fight hard to keep it on the market.

The Hestands said they also learned about a group of dermatologists who saw a pattern that wasn't being studied and began their own study. They documented more than 2,900 cases of suicide in Accutane users in the last three months of 1999, Tammy said. Roche stepped in and said the information wasn't accurate, so patients on any other medications, patients with previous mental health problems, and patients affected by various other environmental factors that might cause them to commit suicide, were removed from the study results. That left 173 individuals with absolutely no extenuating factors except that they took Accutane, David said.

"Sitting here in Bloomfield, we didn't know," Tammy said. "We want our neighbors here to know. We want people in Linton to know."

She said they could sue Roche and possibly receive a settlement, according to the lawyer in Indianapolis, but if they did hit the company in the wallet, they wouldn't be able to talk about it.

"It's more important to let people know what's going on," she said.

Looking around the packed Bloomfield High School Gymnasium during Caleb's funeral service, Tammy said, she couldn't help thinking "You can't tell me no one else in this room isn't on it."

She said she's e-mailed the legislators she read about in Washington, D.C., with the full intent of seeing what she and David can do to help spread the word about isotretinoin's potential dangers.

Both Tammy and David are concerned that people will think they're just looking for someone to blame for Caleb's death. But their goal is to spread the word so people will educate themselves before making a decision about using isotretinoin or letting their child take the medication. Tammy encourages people to look it up on the Internet by using a search engine to search for "Accutane" or "acne and suicide." She said she found everything from FDA information sheets to stories like their own posted by parents.

"We were so ignorant and in the dark that when we started talking about it, we were surprised at the people that did know about it and its side effects," Tammy said. "A lot of people in our family said 'Oh gosh, he wasn't taking Accutane, was he?' "

Family members have been spreading the word in their communities, and the Hestands have received a number of calls from parents who've taken their children off isotretinoin after hearing Caleb's story.

"I'm very comfortable to openly say to anybody, 'This medication took our son,' " Tammy said. "That's it in a nutshell. It doesn't feel any different to me than if a serial killer took him. Some people think it should make us feel better because it wasn't something we did, but it doesn't, because it's something that just should not have been."

Family of Suicide Victim Learns His Acne Treatment Lists Suicide As Side Effect

Tue, 27 Sep 2005 00:00:00 -0700

Tammy and David Hestand of rural Bloomfield are concerned that a prescription acne medication may have contributed to the suicide of their 17-year-old son, Caleb.

"He had the world at his feet," Tammy said. "He had a beautiful life with everything going for him. Then on August 28th he committed suicide with no warning.

"We talked to his friends, our pastor and we can't come up with anything else. Things were good with his girlfriend, his job, his friends. He had a car and money for dates. He was focusing on West Point. He had more freedom than he'd ever had. He had a great summer."

The young man, who would soon have been 18 and was a senior at Bloomfield High School, had an admissions appointment at the United States Military Academy at West Point and was excitedly preparing his paperwork. He was heavily involved in Junior ROTC, participated in track and field, and was in honor society, according to his parents. He planned to study chemical engineering at West Point.

"He was mature and responsible and always on a straight line," Tammy said.

"There wasn't a morning of his life that he didn't wake up and ask 'What can I do for you, Mom?' "

He was a modest kid who voluntarily helped others, as well, the Hestands found out at his funeral service. They said people they didn't even know approached them to say how Caleb had helped them in various ways, such as weeding an elderly person's lawn or bringing an elderly lady her newspaper.

The Hestands said they truly believe everything was fine with Caleb right up to the morning of his death and that his suicide was not planned. David said his son had told his girlfriend he'd be over to help her with her algebra the day he killed himself, and he'd recently invested $2,000 in a gaming computer.

"Things like that just don't make sense," David said.

After Caleb's death, Tammy found an insert for his acne medication, Accutane®, which is marketed by Roche. She was disturbed at what she read.

"One whole side of the insert is dedicated to psychiatric events," she said, adding that she looked up more about it on the Internet.

"I think the most disturbing thing was story after story like ours just change the name.

"Pretty much the overall defense of the pharmaceutical company was that these kids were so deformed by acne that they were suicidal before."

Depression, psychosis (seeing or hearing things that aren't real), thoughts of suicide, and suicide are listed as possible side effects of Accutane®. According to the MICROMEDEX® Healthcare Series, other potential side effects include everything from dry eyes to Crohn's Disease, hearing loss to violent or aggressive behavior, kidney disease to dry, brittle skin, nails and hair. Bruising, chest pain, hyperglycemia, hyperthyroidism, abnormal lipids, increased or decreased appetite, inflammatory bowel disease, ulcerative colitis, nausea and vomiting, pancreatitis, anemia, bleeding, hepatitis, tendonitis, arthritis, arrested growth, muscle damage, headache, confusion, lethargy and fatigue, watery eyes, conjunctivitis, cataracts, night blindness, sexual dysfunction, bronchospasms, and respiratory infections are among other symptoms documented in users of isotretinoin, which is the chemical name for Accutane®. Birth defects, miscarriage and other pregnancy-related risks also are indicated with isotretinoin use.

Once the primary patent on Accutane® expired, other companies came out with their own bioequivalent versions. Sotret®, by Ranbaxy Pharmaceuticals; Claravis, by Barr Laboratories; and Oratane®, by Douglas Pharmaceuticals, are examples. Tammy believes this has made it easier for patients to afford and, therefore, it's prescribed more often.

"You had to have systemic cystic acne to get it at first," she said. "Now kids with a few pimples are getting it. It's much easier now."

Isotretinoin is recommended for severe nodular or cystic acne that's been unresponsive to conventional therapies, including antibiotics. Shelley Rosenstock, executive director for public affairs at Roche, defines cystic or nodular acne as a "chronic (long-term) condition in which painful, disfiguring, fluid- or pus-filled cysts form under the skin of the face, neck, chest and back." She said the risk of scarring is significant. Isotretinoin provides "complete and prolonged remission" for acne. In other words, it clears it up pretty much permanently.

"Accutane® isotretinoin and its generic versions are the only approved and effective treatment for severe cystic or nodular acne that has not responded to other treatments," Rosenstock said. "Healthcare providers worldwide have used it for 23 years to help more than 14 million patients."

She explained that acne is a disease of the hair follicle unit consisting of the hair shaft, hair and oil (sebum) gland. Acne occurs from the interaction of several different factors, including increase in sebum production, obstruction of the hair follicle caused by abnormal cell production, overgrowth of a specific bacteria, and inflammation resulting from the leakage of sebum, bacteria, and other cells into the lower layers of skin. In severe nodular acne, these factors combine to cause nodules, or inflamed lesions, that can be painful and may result in scarring if left untreated, she said.

Isotretinoin treats this form of acne by four different mechanisms, according to Rosenstock. It reduces sebum production by 60 percent to 80 percent; restores proper balance of cell growth and eliminates stickiness in the hair follicle; significantly reduces bacteria on the skin and in the hair follicle; and reduces immune response in the skin by about 98 percent. Normal levels and responses return after treatment, she said.

"The effect of the way the product works usually prevents the acne from returning," Rosenstock added.

Tammy said a dermatologist recommended Accutane® for Caleb, explaining that it was a last resort and that it was controversial. She said he told them about the birth defects and liver issues, but said he was confident in giving it to Caleb. She said her son had to have fasting liver tests before his appointments with the doctor every four weeks.

The Accutane® did clear up Caleb's acne, and there were no noticeable side effects, she said. The only thing they noticed was an uncharacteristic lapse of judgment a couple times during the summer. They chalked it up to feelings of empowerment that come with the freedom teens gain when they hit a certain age.

"I have to give it credit," Tammy said. "It was a miracle drug. His skin was beautiful."

After Caleb's death, she said, the doctor told her he checked Caleb's file to be sure he'd asked him about depression and suicidal feelings. He had, and Caleb had denied any of those feelings. The doctor told Tammy that he'd prescribed Accutane® for 20 years without a problem. Then why, she wondered, did he check Caleb's file when he learned of the teen's death?

Call For Ban On Acne Drug Linked to Suicide

Wed, 21 Sep 2005 00:00:00 -0700

The mother of a talented student who committed suicide after taking an anti-acne drug that has been linked with scores of deaths around the world is calling for it to be banned.

David Roberts, 20, had been taking Roaccutane for three months when he was found hanged from a tree near his home in Allerton, Liverpool.

Data collected by the World Health Organisation indicate that Roaccutane has been implicated in 720 reports of psychiatric problems, including more than 100 suicides and suicide attempts.

Figures supplied by Roche, the manufacturer, show that it has received reports of 84 suicides and suicide attempts, it has been reported.

David’s mother, Anne, said that she had no idea how dangerous the drug was. She told Liverpool Coroner’s Court: “I absolutely believe that David’s death was directly due to the drug he was taking.”

After the hearing Mrs Roberts added: “From what I have since learnt it is clear this drug is a danger to young people. There are too many people suffering from adverse reactions to this drug. We hope the ministers for health in the UK and EU will take action and carry out a thorough investigation. How many more people have to die before they take action?

The Department of Health should revoke the licence to prescribe Roaccutane. A company that manufactures these drugs aimed at young people should be at the inquest to answer to the families. You would think they would want to defend it, Instead they didn’t even show the decency to accept the coroner’s invite to the inquest.”

Roche Pharmaceuticals was rebuked by Andre Rebello, the coroner, for not turning up.

Mr Rebello said: “As Roche were one of the properly interested parties they were advised to come to this inquest. They didn’t even acknowledge my letters.

“For any court to be treated in contempt in that way is not a very good start. They completely ignored notification. They were not charged with blame or liability but simply to give their side of events.”

Roche Products Ltd said that it was saddened by the death. A spokeswoman said: “Unfortunately, severe acne can cause some sufferers to become depressed and can also affect their mood and self-esteem.

“This is why the information provided with Roaccutane carries a warning that some patients may experience mood changes, including an increase in depression.”

The spokeswoman said the information in each pack told patients to tell their doctor if they suffered from depression or if they noticed any change in moods. More than 13 million people worldwide had been successfully treated for severe acne using Roaccutane over the past 20 years. She said that, while no causal link has been established between Roaccutane and depression or suicide, the company monitored all safety databases worldwide.

The drug, a “last resort” treatment for severe acne that can be prescribed only by consultant dermatologists, was used more than 3,000 times last year in Britain.

Mr Roberts, who had been accepted at Manchester University to study pharmacology, had been prescribed the drug by the dermatologist Arun Baratti. Dr Baratti told the inquest that he was aware of rare side-effects caused by Roaccutane, including suicidal tendencies and potential for self-harm. “We ask patients to look out for loss of interest, loss of appetite and changing sleep patterns. If there was any indication of this I would have given him psychiatric assistance.”

The coroner recorded a “narrative verdict” saying that he did not know all the facts surrounding David’s death and probably never would.

FAMILIES, DEATH AND BLAME

Liam Grant, 20, died in 1997. His father has claimed his son’s suicide was a side-effect of his use of Roaccutane. He has spent hundreds of thousands of pounds on independent research to try to prove that the drug causes depression.

In November the family of Jon Medland, a medical student who killed himself after taking the drug, called for a worldwide inquiry into Roaccutane. Mr Medland, from Barnstaple, Devon, was in the final year of his medical degree at Manchester University when he hanged himself at his student lodgings. His inquest was told that Mr Medland changed from a “bubbly, outgoing” young man to withdrawn and depressed with suicidal thoughts.

In 1997 Seumas Todd, the 20-year-old son of Richard Todd, the actor, committed suicide after taking Roaccutane. His father believes that the drug was “undoubtedly” a factor in his death.

Isotretinoin-Related Birth Defects

Fri, 16 Sep 2005 00:00:00 -0700

Isotretinoin (also known as Accutane) is a drug used to treat severe acne, but it can cause birth defects when taken by pregnant women.

Because of these risks, the U.S. Food and Drug Administration and Roche Pharmaceuticals (Accutane's manufacturer) developed a voluntary pregnancy prevention program (PPP) in 1988 to try and prevent conception in women taking the drug. This program was replaced in the U.S. in 2002 with the System to Manage Accutane Related Teratogenicity (SMART), a program that placed more emphasis on pregnancy testing and contraception.

A study published online October 14, 2005 in Birth Defects Research (Part A): Clinical and Molecular Teratology (www.interscience.wiley.com/journal/bdr) surveyed pregnant women who contacted a birth defect information service seeking information on the effects of isotretinoin. The purpose of the survey was to determine how the drug was dispensed in women who subsequently became pregnant and to identify possible reasons for failure in preventing conception.

Led by Julia Robertson of the Birth Defects and Genetics Program at the Utah Department of Health in Salt Lake City, researchers surveyed 34 women who had called a member service of the Organization of Teratology Information Services (OTIS) between April 2002 and September 2004 because they had become pregnant while taking isotretinoin. "The results of the OTIS survey show that the majority of women who participated were treated for less severe disease than is recommended in the SMART program," the researchers state.

A total of 24 percent of the women reported receiving contraception counseling while taking the drug. In addition, the results showed that healthcare professionals and their patients failed to comply with a number of key SMART and/or PPP requirements. According to these requirements, women must have two negative pregnancy tests before receiving a prescription, yet 76 percent of the women in the study said they did not have a second pregnancy test during menstruation.

When asked about the SMART requirement of receiving a pregnancy test each month before refilling a prescription, 35 percent of the women surveyed said they did not have monthly pregnancy tests during the therapy. SMART also requires women to use two forms of birth control simultaneously while taking isotretinoin, yet only 62 percent of the women reported using birth control and only 29 percent of these women reported using two forms of contraception. In addition, only 53 percent of the women reported signing the informed consent required by SMART prior to taking the drug.

The authors point out that the study's strengths include using counselors with extensive experience in communicating with women about their reproductive concerns and the fact that most initial interviews were completed within 3 months of exposure, before fetal outcome was known. They acknowledge that the study's limitations include the small number of women surveyed and the fact that responses are based on patient self-reporting and may be subject to recall error. "Nonetheless, women were surveyed prior to the outcome of the pregnancy, so we believe the responses provided in this report can be useful in elucidating important factors that hinder the success of pregnancy prevention programs," the authors state.

Last year, the FDA began examining ways of designing a new pregnancy program with stricter requirements to prevent isotretinoin-related birth defects and in August 2005 the new plan, called iPLEDGE, was announced. Beginning December 31, 2005, the regulations will require doctors and patients to register in an electronic database before the drug can be dispensed. The plan also includes the two pregnancy tests, two birth control methods, and other safeguards previously recommended by SMART.

Despite Severe Warnings and a New Registry Program, Many Question Whether an Acne Drug Is Really Worth the Enormous Risks Posed by Accutane

Sun, 28 Aug 2005 00:00:00 -0700

For years, Accutane has been under siege from numerous medical experts, consumer watchdog groups, and even many officials within the FDA itself because of the many serious health risks linked to the drug.

One problem associated with the current FDA approval and review process that is quite troublesome, is the dramatic increase in the harm or risk that will be tolerated when weighing the potential benefits of a new prescription drug.

Traditionally, even drugs which promised significant benefits would be subjected to greater testing over longer periods of time when significant side-effects or adverse reactions were possible. If the drug was developed to treat a relatively minor condition, the possibility of dangerous side effects usually spelled the end of the drug in terms of FDA approval for marketing.

Today, however, drugs are routinely given FDA approval without sufficient long-term testing using large study groups and without adequate warnings despite evidence of significant side-effects and adverse reactions. Drugs are also permitted to remain on the market far longer than they should be once significant problems are suspected or even confirmed.

This has repeatedly resulted either in the need for upgraded warnings one or more times after a drug is already on the market or in dangerous drugs being pulled from the market only after causing numerous serious injuries or deaths.

Probably the most alarming situation today, however, is when a drug designed to treat a relatively minor condition is approved by the FDA and permitted to remain on the market despite clear evidence of significant side effects or adverse reactions.

In such cases, the risk versus benefit equation has all but vanished from the pharmaceutical companies’ consideration and the FDA’s standards. Accutane is an example of such a drug.

For all of the positive results it might have achieved, Accutane is still nothing more than an acne drug. This fact alone has caused a wide range of critics of the drug to wonder how it has been permitted to remain on the market at all.

Recent developments with respect to the drug and the manner in which Accutane is regulated and monitored requires a fresh look at the drug and its uncanny ability to survive when other drugs used to treat far more serious conditions with considerably less serious side-effects have been pulled from the market.

Accutane is manufactured by Hoffman-LaRoche Pharmaceuticals. Its active ingredient is known as isotretinoin and it is primarily used to treat nodular acne, a condition that is resistant to other treatments, including antibiotics, and is characterized by the appearance of many nodules or cysts.

These nodules are inflammatory lesions filled with pus and get lodged deep within the skin. The lesions can cause pain, permanent scarring, and negative psychological effects.

Since its approval in 1982, Accutane has been linked to serious potential side-effects including:

•    birth defects when taken by pregnant women
•    psychological problems including possible suicide
•    neurological problems
•    stomach, bone and muscle problems
•    hearing and vision problems
•    problems with fats and cholesterol in the blood
•    ulcerative colitis
•    Crohn’s disease
•    inflammatory bowel disorder
•    rectal bleeding
•    abdominal pain
•    central nervous system injuries
•    bone and muscle loss
•    cardiovascular injuries
•    liver and kidney damage
•    pancreatitis
•    immune system disorder
•    lupus
•    thyroid disorders
•    various allergic reactions
•    Some minor side effects include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds.

In 1998, the Food and Drug Administration advised doctors who prescribe Accutane to watch their patients for signs of depression. Afterward, Hoffman-LaRoche, the maker of Accutane, notified doctors that the drug “may cause depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide.”

This was one of the first indications that Accutane was headed for further problems. In January 2001, Roche began mailing doctors, psychiatrists, and pharmacists, information about the recent discovery of links between Accutane and various psychological problems.

By that time, the FDA had already received reports concerning 66 suicides and 1,373 cases of psychiatric problems. The drug’s information packet had already been updated in 1986 to include information about links between Accutane and depression.

Birth defects are perhaps the most severe side effects to be linked to Accutane. The list of possible birth defects include: hydrocephaly (enlargement of the fluid-filled spaces of the brain); microcephaly (small head); heart defects; facial deformities; and mental retardation.

The warnings originally released with Accutane in 1982 designated it as Category X, which means that it must be avoided under all circumstances by pregnant women and nursing mothers. Yet in 1983 reports of babies being born with certain defects began to surface.

As a result, in 1988, Roche launched the Pregnancy Prevention Program (PPP) with a kit that included a contraceptive booklet, checklists to help assess whether patients could comply with the drug’s requirements, and a consent form for patients to sign stating that they were fully aware of the risk of birth defects.

In 2001, Roche and the FDA also developed what is known as the System to Manage Accutane-Related Teratogenicity (SMART), a plan which requires those female Accutane users in their childbearing years, who have not had hysterectomies, to take and submit a pregnancy test every month before receiving a 30-day refill of the medication.

Since Accutane’s market approval, there have been 2,000 incidences of pregnancies among users, many of which ended in abortion. The FDA, however, has calculated that more than 160 babies were born with defects directly attributable to Accutane usage.

It is likely that there were actually more pregnancies that occurred in female Accutane users because there was no system for reporting Accutane-linked pregnancies at the time.

Apparently, however, these precautions and amendments relating to Accutane were not enough to prevent the continuation of some of the most severe side effects associated with the drug.

Reports of suicides and birth defects relating to Accutane continued to surface forcing the FDA and Roche to once again review Accutane’s warning label.

In May of 2005, a new study published in the American Journal of Psychiatry suggested that Accutane can actually change brain functioning. This is the first study to monitor brain functioning of Accutane patients and the first to show a direct biological link between the drug and depression.

The team of psychiatrists conducting the study found that the group of young adults taking Accutane showed decreased brain functioning of up to 21% in the front part of the brain an area known to mediate symptoms of depression.

The authors of the study have now urged the FDA and Hoffman-La Roche to conduct further research on the drug. Accutane has now been linked to 266 cases of suicide in the United States including some high-profile cases such as the death of U.S. Congressman Bart Stupak’s son.

Just this past month, the FDA announced that there would be a new National Registry for all Accutane users that will take effect in December 2005. Both male and female patients will have to enroll in the registry as well as doctors and pharmacies.

The purpose of this registry, called iPLEDGE is to eliminate the risk of birth defects by strictly monitoring female patients to make sure that they are not pregnant when beginning treatment and that they do not become pregnant during treatment.

Until now, women of childbearing age have been required to use two forms of birth control, get two negative pregnancy tests before their first Accutane prescription, and show proof of another negative pregnancy test before each refill.

The computerized registry system will now make sure that these precautionary measures take place as each woman will have to enter this information into the registry either by phone or by internet.

While the registry doesn’t officially begin until December, it opened on August 22 in order to allow doctors, patients, and pharmacies time to understand how to use it before everyone signs on at the end of the year.

In addition to taking part in the registry, all patients will also have to read, review, and sign a document informing them of the risks associated with Accutane, specifically psychiatric side effects and pregnancy-related issues.

The March of Dimes, a national voluntary health agency whose mission is to improve the health of babies by preventing birth defects, premature birth and infant mortality, applauds the recent efforts of the FDA. Still, the organization has its doubts about the new registry.

For one thing, the registry will not regulate internet sales, therefore people can still acquire Accutane over the internet without understanding the severity of the health risks associated with it.

There is also concern that people might get confused with the many generic forms of isotretinoin and may still end up taking Accutane and putting themselves at risk without even knowing it.

In their alert regarding Accutane released in May of 2005, the FDA advised all Accutane patients to discontinue usage of the drug and inform their health care professional immediately if they experienced any of the following symptoms:

•    Feelings of sadness or crying spells
•    Loss of interest in activities once enjoyed
•    Sleeping too much or having trouble sleeping
•    Having increased irritability, anger, or aggressivity (i.e. temper outbursts, thoughts of violence)
•    Change in appetite or body weight
•    Trouble concentrating
•    Withdrawal from family or friends
•    Loss of energy
•    Feelings of worthlessness or inappropriate guilt
•    Thoughts of self-harm or suicide

In some situations, discontinuing the drug may not alleviate the problem and psychiatric evaluation or further medical investigation may be necessary.

Currently, litigation involving the following injuries is either in progress or being considered in a number of states:

•    Inflammatory Bowel Disease
•    Premature Closure of Growth Plates
•    Birth Defects
•    Ulcerative Colitis
•    Crohn's Disease
•    Inflammatory Bowel Syndrome
•    Rectal Bleeding
•    Abdominal Pain
•    Central Nervous System Injuries
•    Bone and Muscle Loss
•    Cardiovascular Injuries
•    Liver and Kidney Damage
•    Pancreatitis
•    Immune System Disorder
•    Lupus
•    Hearing and Vision Damage
•    Thyroid Disorders

Many experts and consumer advocates believe the range of serious health risks (physical and psychological) associated with Accutane should have doomed the drug long ago. The fact that it is nothing more than a treatment for acne (regardless of how serious it may be) makes its survival all the more astounding to its critics.

FDA Puts New Restrictions on Accutane

Sat, 13 Aug 2005 00:00:00 -0700

The thousands of Americans who take the acne drug Accutane and people who prescribe and dispense it must enroll in a national registry, part of a major government program to tighten access to the medicine that causes birth defects.

The Food and Drug Administration enacted unprecedented curbs Friday in trying to keep Accutane and its generic competitors on the market while ensuring that women who use the risky pills don't get pregnant. Critics see it as the drug's last chance, after two decades of safety warnings and other restrictions failed to end Accutane-damaged pregnancies.

"This is a system that has been long in the works and many would say is long overdue," acknowledged Dr. Sandra Kweder, FDA's deputy drug chief. "The responsibility for ensuring that fetuses are not exposed to this medicine is enormous, and is shared by everyone" who takes, prescribes or sells it.

If a woman becomes pregnant while taking the acne drug, her baby can suffer severe brain and heart defects, mental retardation and other abnormalities, even if the mother took only a small dose for a short period. That's a risk for 30 days after stopping the drug, too.

Under the program, every patient men and women must enroll in the iPLEDGE computerized registry starting Dec. 31 to receive Accutane or generic versions of the drug isotretinoin.

Doctors must register, too, if they wish to continue prescribing the pills. Drugstores and wholesalers also must register in order for the pills' manufacturers to ship them any supplies.

How does the program work?

All patients seeking a prescription must sign a document informing them of Accutane's risks, including the possibility that it contributes to depression or suicidal thoughts — a warning on the drug's label that FDA also strengthened Friday.

Patients must agree to monthly doctor visits for refills and not to share the pills with anyone. Then the doctor registers each patient into the iPLEDGE database, giving him or her a special identifying code number, and writes the prescription.

But for women of childbearing age, there are some additional steps:

_They must undergo two tests to ensure they're not pregnant in a laboratory or doctor's office before the initial prescription, and monthly pregnancy testing before each refill. Home pregnancy tests don't count. The doctor must enter the pregnancy test results into the iPLEDGE system, and the woman must buy her pills within seven days.

_These women also must agree to use two forms of birth control while using Accutane, and must self-register on iPLEDGE — in addition to the doctor's initial registration — to report that they're doing so. There's no way to know if women lie in this step, but FDA sees it as an additional opportunity to warn of the pills' danger.

The pharmacist must check the computer database before filling a prescription to ensure that patients followed all these rules. Accutane manufacturer Hoffman-La Roche and generic manufacturers will monitor drugstores and wholesalers, and are supposed to cut off violators' sales supplies.

Accutane is supposed to be used for severe acne only, but it is widely acknowledged to be prescribed for more minor cases. The FDA estimates that 100,000 prescriptions for Accutane and generics are filled each month.

"We are very happy that this has happened and wish it had been done years ago," said Dr. Nancy Green, medical director of the March of Dimes.

But the organization, which fights birth defects, will be watching closely to see if the program stops fetal exposure to the risky pill something tough to do considering the acne drug's chief market is young people, and that half of all U.S. pregnancies are unplanned.

"If it looks like this is a leaky system despite FDA's efforts to really step it up, we may very well call for it to be taken off the market," Green warned.

Since Accutane began selling in 1982, the FDA has reports of well over 2,000 pregnancies among users. The vast majority ended in abortion or miscarriage, but the FDA counts more than 160 babies born with drug-caused defects. Critics note there likely were many more pregnancies because doctors haven't been required to report Accutane-linked pregnancies. Friday's new rules mandate that they do.

FDA first attempted to tighten Accutane access in 2001, but the restrictions were largely voluntary and didn't work: The FDA counted 120 pregnancies among the drug's users in the first year of that program, just seven fewer than in the previous year even though overall prescriptions dropped by 23 percent.

The registry actually opens on Aug. 22, giving users extra time to learn how it works before the provisions become mandatory at year's end. On that date, patients may enroll at http://www.ipledgeprogram.com or by phone at 1-866-495-0654.

FDA Increases Restrictions on Acne Drug

Sat, 13 Aug 2005 00:00:00 -0700

Although welcomed by some experts, the FDA's actions are unlikely to satisfy critics who say the agency has neglected its duty as a drug safety watchdog. Accutane has been on the market for many years, and these critics say the measures the FDA has taken will not keep doctors from prescribing it to patients who may not need such strong medicine.

Accutane was one of five drugs named in the fall in congressional testimony by FDA whistle-blower Dr. David Graham as deserving a critical reexamination of their risks and benefits. In an interview Friday, Graham questioned whether the new monitoring program would work.

"It will not sufficiently reduce the use of Accutane for less severe forms of acne," said Graham, a drug safety officer.

"A restricted distribution system should have been in place 15 years ago, and FDA scientists from both the drug safety office and the [drug] reviewing division were urging that it be adopted," he added.

It is fairly common for regulators to restrict access to powerful drugs, and patient registries are a standard tool for closely monitoring safety, but a computerized system involving so many players is new territory for the FDA.

"This is a system long in the works, and many would say it is long overdue," said Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs. "The responsibility that fetuses not be exposed to this medicine is enormous and is shared by everyone who participates" in distributing, prescribing or taking the drug.

About 100,000 prescriptions a month are written for Accutane or its generic equivalent, isotretinoin. Although the FDA says it should be used only to treat a disfiguring condition known as severe recalcitrant nodular acne, doctors are free to prescribe it as they judge best.

Graham said an estimated 3,000 to 4,000 women a year get pregnant while taking Accutane, and most opt to have abortions. Other drug experts said the FDA's actions were an encouraging sign.

A more comprehensive tracking system was needed because current efforts have not been effective in keeping women from getting pregnant while using the drug, said Dr. Brian Strom, chairman of the biostatistics and epidemiology department at the University of Pennsylvania School of Medicine.

"This has been a public health dilemma," Strom said. "It is an extraordinarily effective drug. Simply put, you take it for four months and your acne goes away for life. But it's also extremely effective at causing birth defects. How many birth defects and how many abortions are acceptable? But the flip side is, do you deny this drug to men and women who are responsible about how they take it?"

Strom was a member of an FDA advisory committee that more than a year ago recommended much more stringent precautions for patients taking Accutane, including monthly pregnancy tests.

The FDA's new tracking system, called iPledge, will go into effect Dec. 31. Wholesalers, pharmacies, doctors and patients will have to register with the system to sell, prescribe or take Accutane and its generic versions. Patients will be able to register on the Internet or through a toll-free number.

All patients will have to acknowledge that they have been counseled about the risks of Accutane. Women of childbearing age will have to provide two negative pregnancy tests before starting to take the drug, a negative pregnancy test every month while taking it and another negative test a month after their treatment ends. Home pregnancy tests will not be accepted.

Women must also agree to use two forms of birth control during treatment or to abstain from sex.

Doctors and pharmacists will access the iPledge system when prescribing and dispensing the drug. If a patient is not registered in the system, or if pregnancy test results are missing, pharmacists will not be able to fill a prescription.

Accutane manufacturer Roche said it strongly supported the new system.

Top seller

The FDA introduced a system to track the distribution and use of pills containing isotretinoin, the active ingredient in Accutane and its generic competitors. Isotretinoin carries a risk of birth defects if it is taken during pregnancy.

Market share for all prescription acne drugs in 2004

Accutane: 31.6%

Amnesteem: 21.9%

Retin-A Micro cream: 12.7%

Tretinoin cream: 9.3%

Claravis: 7.6%

Other: 16.9%

(Generic isotretinoin is also sold as Sotret (not shown) and under the chemical name Accutane)

FDA Launches Site to Warn Patients, Doctors of Drug Risks

Fri, 20 May 2005 00:00:00 -0700

The U.S. Food and Drug Administration has begun issuing alerts to patients and doctors on its Web site about emerging drug-safety concerns, including dangers posed by drugs prescribed for unapproved purposes.

The new site, called Drug Watch, marks a significant change in how the agency communicates risks to the public. In the past, the FDA has spent months or years privately weighing and debating risk information with drug companies until a final determination was made on the scientific significance of the danger.

After being bashed by Congress and consumers for its slow response to emerging information about heart risks posed by blockbuster pain medications such as Vioxx, the FDA now is beginning to make risk information available to the public much sooner.

"This is really a fundamental change," said Dr. Steven Galson, the acting director of the FDA's Center for Drug Evaluation and Research. "We do intend to give companies a heads up before posting something new about their drugs, but we're not going to discuss it with them. They're not going to review it."

The safety alerts posted so far on the site http://www.fda.gov/cder/drugSafety.htm are notable also because they emphasize risks posed by doctors prescribing drugs for purposes never approved by the FDA. It's a practice called "off-label prescribing" because it involves using drugs in ways and to treat conditions not covered by the safety and effectiveness determinations on their FDA-approved labels.

"That's a very important aspect of this," Galson said. "As you know, we don't regulate the practice of medicine. We have no way of preventing physicians from using drugs off label."

But Galson said the agency does have a responsibility to let people know about known risks of off-label uses. "This is very controversial, of course," he said.

Some off-label drug uses are beneficial and based on good science, others have little proof of effectiveness and still others have been proved worthless in studies.

Officials at the American Medical Association, which represents doctors, and the Pharmaceutical Research and Manufacturers of America, which represents drugmakers, declined to comment, saying they are evaluating the Drug Watch site and will submit formal comments to the FDA.

Ed Sagebiel, a spokesman for Indianapolis-based drugmaker Eli Lilly, said the company generally supports the FDA's new effort. The site includes alerts for Eli Lilly drugs Prozac, warning of suicide risks related to it and other antidepressants, and Zyprexa, warning of an increased risk of death when it and other atypical antipsychotics are prescribed off-label to treat dementia in elderly patients.

"We just want, from our standpoint, to properly balance warning people and patients of safety concerns without frightening them or inadvertently making them stop taking their medicines," Sagebiel said.

Galson said others in the drug industry have expressed similar concerns. "They're worried we may be over-warning and dissuading patients from using products that may do good," he said. "We expected we would get that sort of push-back."

Advocates for patients called the site an incremental move in the right direction, even though it requires patients to seek out the information on the Internet, rather than it being given to them when they pick up their medicines. The emphasis on early and off-label risk information is a departure for the FDA, they said.

"I don't think they had the political courage even a few years ago to take these kinds of steps," said Larry Sasich, a pharmacist with Public Citizen's Health Research Group, a consumer watchdog that publishes a searchable database of drug risks at www.worstpills.org.

Sasich said he thinks the FDA is realizing that the only way to change risky prescribing is for consumers to know more about the drugs they take. Changing the official labeling on drugs and sending letters to doctors about new risks hasn't worked, he said.

Sasich expressed concern that elderly patients who are the biggest consumers of prescription drugs won't have enough access to Drug Watch information that's available only on the Web.

Cynthia Pearson, the executive director of the National Women's Health Network in Washington, praised the direct communication of risks listed atop several drugs on the site.

"Our position always has been: Get people access to good information and they can make good decisions," Pearson said.

The Drug Watch site, still being developed, lists information on about 200 drugs. Most of them include routine prescribing information. Among those tagged with an "FDA Alert:"

Accutane, a drug for severe acne. "The FDA continues to assess reports of suicide or suicide attempts" associated with this drug. All patients "should be observed closely for symptoms of depression or suicidal thoughts," the alert warns.

Cytotec, also called misoprostol, a drug approved to prevent ulcers. The alert warns of risks in its off-label use in labor and delivery. "These uses are not approved by the FDA. No company has sent the FDA scientific proof that (Cytotec) is safe and effective for these uses. There can be serious side effects, including a torn uterus..." the alert warns.

Zyprexa, Risperdal and several other psychiatric drugs called atypical antipsychotics. The FDA warns that when prescribed off label as a treatment for dementia, older patients "had a higher chance for death than patients who did not take the medicine."

Amiodarone, marketed also as Cordarone and Pacerone, a popular heart drug approved only to treat a specific life-threatening rhythm disorder. It is widely prescribed off label for non-life-threatening atrial fibrillation. The alert warns of potentially fatal side effects including lung toxicity, liver injury and worsened heart rhythm problems.

Gabitril, a drug approved to treat seizures. The alert warns that it risks causing seizures when used off label. Gabitril's "safety and effectiveness have not been established for any other use," the alert notes, adding that the drug's maker, Cephalon, will be educating doctors "to discourage off-label use."

Sheryl Williams, a Cephalon spokeswoman, said through Drug Watch, the FDA appears to be trying to do a better job of communicating and addressing the increasing prevalence of off-label prescribing.

A Knight Ridder investigation published in 2003 found that patients are being injured and killed when doctors routinely prescribe medications in ways that the FDA has never approved as safe and effective. Off-label prescriptions for top-selling drugs accounted for nearly a quarter of their retail sales.

Williams said most of the prescriptions that doctors write for Gabitril are to treat psychiatric conditions - not epileptic seizures. Bipolar disorder is a particularly popular use, she said.

"The problem is there is no guidance for them to do so. We haven't done double-blind studies. We haven't even done single-blind studies," Williams said. "Our scientific team doesn't believe there is sufficient evidence that a drug like Gabitril would be effective in bipolar disorder."

While Gabitril is effective in reducing the frequency of seizures in people with epilepsy, she said, when used off label the drug has been associated with seizures in people without epilepsy.

Study Finds Acne Drug Can Affect Brain

Tue, 03 May 2005 00:00:00 -0700

A new study suggests Accutane, the controversial acne treatment that has been linked to suicide, can change brain functioning.

As a result, the authors of the study urged the Food and Drug Administration and the drug's manufacturers, including Nutley- based Hoffmann-La Roche, to conduct further research into a medicine that is regularly prescribed to millions of Americans each year.

"The drug can cause symptoms of depression in a small percentage of people, so there should be screening for psychiatric disorders before going on the medication," Douglas Bremner, the lead author and an Emory University psychiatry professor, said.

The study, which was published in the American Journal of Psychiatry, is the latest salvo in an ongoing debate over the safety of the drug. Approved in 1982, Accutane has been blamed for birth defects and its usage is more closely monitored than other medicines.

The findings also come amid a heated controversy over the safety of prescription medicines. The issue erupted last fall after Merck withdrew Vioxx and concerns were raised over side effects caused by several antidepressants.

The latest study is the first to attempt to monitor brain functioning of Accutane patients and follows charges made last fall by an FDA medical reviewer that Accutane is one of five dangerous drugs that should not be on the market.

Concerns over Accutane and psychiatric side effects aren't new, though.

A growing number of lawsuits have charged the medicine causes suicide. Court documents in Florida revealed Roche's internal estimates show the depression rate is 1.5 times higher among Accutane users, according to a published report last year.

Three years ago, the FDA issued new prescribing instructions for physicians and required Roche to update the drug warning label to reflect psychiatric side effects. To date, Accutane has been linked to 266 cases of suicide in the United States and overseas, according to the FDA.

Nonetheless, many doctors say teenagers with acne may suffer depression. A Roche spokeswoman, Shelley Rosenstock, yesterday repeated earlier arguments that no scientific evidence links Accutane to suicide. She also challenged the methodology of the new study.

An FDA spokeswoman, meanwhile, said the agency will continue to monitor information about Accutane, as well as three newer generic versions, and will review the study. However, critics say the FDA has not paid sufficient attention to suicide links.

"Without tighter distribution controls and further research into the cause of these potentially deadly side effects, the FDA cannot tell the American people it is adequately protecting their health and the health of their children," said U.S. Rep. Bart Stupak (D-Mich.), whose son committed suicide while on the drug.

The new study scanned the brains of 28 healthy men and women whose median age was 26. Funding was provided mostly by an accountant in Ireland, whose teenage son committed suicide while taking Accutane several years ago, as well as several lawyers.

Nashville Beautician Warns of Acutane Dangers

Fri, 25 Mar 2005 00:00:00 -0800

In an age where concerns about Accutane are widespread, some students are beginning to turn to a series of facials, a potentially safer alternative to treat acne.

Nicole Diamond, a local beautician, said that a six-week treatment plan of facials and related products is safe and extremely effective.

"Far more people are prescribed Accutane than actually need it," Diamond said. "Accutane is an extreme, and it has become a common solution."

Diamond's plan includes glycolic-based facials and the popular M.D. Formulations skin products. Her plan is particularly geared towards acne-prone individuals, but she also has facials for wrinkled and sun-damaged skin.

And Diamond's method has always given results.

"I have seen significant improvement of breakouts every time," says Diamond. Some of Diamond's satisfied customers include Vanderbilt students, who prefer her treatments to Accutane and other therapies.

"My skin has totally turned around since I did the treatment plan. I don't wear makeup in the day anymore!" says senior Amy Elhoff.

Diamond offers other beauty services to her clients, particularly waxing.

"Nicole does the best waxing job of anyone I have ever met," says senior Mollie Mulloy.

Diamond considers her profession more than just a job--to her it is a form of art.

"I see the face as a canvas. I like helping people look and feel the best they can," says Diamond.

Customers of the Look Salon where Diamond performs facials and waxes are satisfied with both service and atmosphere.

"Nicole is not just great at what she does, she's a great person," says Elhoff.

The local beautician has given facials and waxes to celebrities from Nashville to Los Angeles (Diamond recently moved from California). She also sells the popular Bare Escentuals all-natural cosmetics and treatments that are guaranteed not to clog pores.

In addition to her salon services, Diamond models and sings, giving her an inside perspective on beauty services in the entertainment industry.

Grieving Father Spends $1 Million Nest Egg To Investigate Accutane

Wed, 26 Jan 2005 00:00:00 -0800

Liam Grant says he's sure his son's acne medication caused the Irish university student to commit suicide.

So sure he's spent roughly $1 million of his retirement nest egg on scientific research examining the effects of Accutane, the acne drug manufactured by Roche.

So sure that he helped organize a Web site aimed at restricting use of the drug and investigating what the manufacturer knows about its safety.

And so sure that he rejected a settlement offer from Roche and several co-defendants that could total at least hundreds of thousands of dollars.

Early next month, Grant is scheduled to square off with a division of the Swiss-based pharmaceutical giant for a hearing in a Dublin court. If he prevails at the proceeding, which comes as a U.S. congressman seeks a Washington hearing on Accutane's safety, Grant could move closer to obtaining internal company records about the drug. That, in turn, could provide legal ammunition for plaintiffs in roughly 70 pending Accutane cases in the United States, where there have been few settlements involving suicide or depression.

The 57-year-old forensic accountant says he's optimistic about the David vs. Goliath confrontation. "How do you bring an elephant to the ground? Small bites," said Grant during one in a series of recent telephone interviews. "That's what I'm doing. Small bites."

In response, the company said: "Roche feels a great deal of sympathy for Liam Grant regarding the loss of his son, but according to a significant body of scientific evidence, there is no cause-and-effect relationship between Accutane and psychiatric events."

Accutane, introduced in the USA in 1982 to treat severe acne that fails to respond to other drugs, is safe when prescribed and used appropriately, Roche says. Many dermatologists and acne patients also say it's more effective than other drugs.

However, the drug has been linked to birth defects among children of pregnant women who have taken it. A Food and Drug Administration researcher told a Senate committee in November that Accutane was one of five drugs that should be studied for potential withdrawal from the market. Moreover, since the late 1990s Accutane's label has warned that adverse reactions reported by some users include "depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide."

But regulators in the USA and Europe hadn't yet required that warning when Grant's 19-year-old son, also named Liam, went to his family doctor in November 1996 for acne treatment.

The younger Grant, one of four siblings, was an engineering student at University College Dublin. His father says Liam played guitar and drums in bands and hoped to launch a career recording music.

Medical records show that Liam did not suffer from the severe, treatment-resistant acne for which Accutane is prescribed. Dr. Pamela Mangal prescribed an antibiotic, then wrote a stronger prescription in December when Liam was unhappy with the results. One month later, she referred him to Dr. Gillian Murphy, a dermatologist, who prescribed Roaccutane, the drug's market name in Ireland. Liam started taking it in February 1997.

His father says he should have noticed the potential warning signs that ensued. Liam, previously outgoing and enthusiastic about his plans, increasingly spent time alone in his bedroom. When friends called, he asked one of his brothers to tell them he was unavailable.

Jury investigates

In June 1997, Liam was found dead, hanging from a tree outside Dublin. A jury, impaneled to investigate the case, ruled the death a suicide and called for more research on Accutane and its side effects.

Grant, backed by his wife, Loyola, and three surviving children, took on the mission.

First, he hired a local scientific researcher to check the drug's history. She discovered that France had added a suicide warning to Accutane's warning label in 1997, during the time Liam had taken the drug.

Grant said he wrote to dermatology associations asking them to conduct research on the possible brain effects of Accutane or urge Roche to undertake such studies. Receiving no response, he decided on an unusual scientific research program: He'd fund some study costs himself by selling two real estate properties he'd bought as part of his retirement portfolio.

He sought out scientific experts at universities in the USA, with the aim of prompting unprecedented research about Accutane. In Massachusetts, he made contact with the University of Massachusetts Medical School and the Eunice Kennedy Shriver Center. In Atlanta, he contacted Emory University.

Although rare, the move isn't unprecedented. Cure Autism Now is a group founded by families to raise funds and seek research that would help relatives suffering from the mysterious disorder. Similarly, Texas billionaire H. Ross Perot paid for research on illnesses afflicting U.S. soldiers who served in the 1991 Persian Gulf War.

So far, Grant funded two studies aimed at securing government grants for additional Accutane research. Results from one, published last April in the Proceedings of the National Academy of Sciences, showed that the active component of Accutane reduced cell creation in the brains of mice that had received clinical doses. In turn, that outcome appeared to impair the mice's ability to learn a maze task.

Could the medication have a similar effect on the human brain? "We can suggest it is a possibility, but we can't say that's the case absolutely," said Peter McCaffery, a University of Massachusetts Medical School researcher who worked on the project.

The second study is undergoing scientific peer review, a vetting process designed to spot any weaknesses or mistakes, in preparation for March publication in the American Journal of Psychiatry. Twenty-eight acne sufferers underwent initial brain scans, along with psychological tests that ruled out any connection between their acne and whether they felt depressed.

For four months, the patients received either Accutane or an antibiotic. New scans conducted on the group afterward showed the Accutane patients had decreased activity in an area of the brain thought to be involved with regulating mood.

"What we can say is that Accutane affects brain function ... and the areas that are affected are the areas involved with depression," said Dr. J. Douglas Bremner, who led the research project at Emory University Hospital in Atlanta.

Grant concedes that some might argue that his personal stake could raise doubts about the integrity of the research. He said he tried to guard against that by channeling the funding through the respective universities involved and required that the study results be published, "no matter what the outcome."

"If you're a scientific researcher, you have a responsibility to do the best work you can while being objective," said Bremner. "In our case, the study showed a change in brain function. That's not something that's an interpretation one way or the other."

Roche responds

Roche, however, questioned the studies and Grant's advocacy role in funding them.

Commenting on McCaffery's research with mice, the company said: "It is widely recognized that animal studies are not predictive of human behavior as it relates to depression and suicide."

Roche said there is no scientific unanimity that the area of the human brain studied by Bremner definitely mediates depression. The company also noted that Bremner's tests showed no differences in severity of depression symptoms among the patients who received Accutane or an antibiotic.

While noting that it's common for pharmaceutical companies to fund drug research, Roche said, "It is quite another matter, in our view, for a plaintiff in a lawsuit to fund a study to support his allegations where there are no published studies that even suggest a cause-and-effect relationship between Accutane and psychiatric events."

Roche also cited three other scientific studies that showed Accutane was not associated with increased risk for depression, other psychiatric disorders or suicide. The studies, funded by Roche, include one that found similar risk rates among more than 7,500 acne patients who took Accutane and nearly 14,000 who took antibiotics.

Grant has cited the differing results of the studies he funded along with other scientific and legal information about Accutane on a Web site (www.accutaneaction.com) that features contributions by individuals and families who say they have suffered serious medical side effects from the drug. Their goal, stated on the Web site, is to prompt a coordinated international investigation of Accutane.

"I don't let this take over my life," said Grant, who explains that he pursues his mission with the investigative approach he uses in his accounting work. He even stopped reading letters from families whose loved ones allegedly died or suffered other serious Accutane-related side effects, "because it got to be too much emotionally."

While preparing for next month's court hearing, however, he has kept in touch with others fighting Accutane battles. One is Rep. Bart Stupak, D-Mich., who is seeking a new congressional hearing on the drug he blames for his own son's suicide. Grant has also spoken with U.S. lawyers interested in any Irish court decision that could support their own Accutane cases.

In a Sept. 7 letter, a Dublin law firm representing Roche and other defendants said the group, though sympathetic about the death of Grant's son, bore no "responsibility for his death." But, even while predicting that position would ultimately be vindicated in court, the letter offered a settlement.

Under the deal, the defendants, including Roche, would pay the maximum damages Grant would be entitled to under Irish law, plus related legal costs. However, the letter stated the settlement would come "strictly without any admission of liability." Responding to questions from USA TODAY, Roche said, "It made financial sense to offer to settle rather than incur the costs of a protracted legal battle" because Ireland has a statutory limit on awards in such cases.

Grant estimated any settlement could total nearly $1.5 million, including the research costs which Roche says it does not intend to pay. But he rejected a deal, even knowing that defense attorneys would likely seek a court-ordered end to the case on grounds he had turned down everything he might ultimately win in court. "That's wrong," says Grant. "Because what I can get from a court is a ruling that Accutane caused the death of my son and that Roche knew that the drug was a serious risk."

Even if the hearing goes his way, Grant faces at least a year of additional legal procedures before a trial that could produce the verdict he's seeking. He says he's determined to fight on, based on "a conviction that I'm 100% correct."

"The death of one person from this drug is too many," Grant said. "Somebody had to say stop. And that person happened to be me."

Five Brands of Risk

Tue, 07 Dec 2004 00:00:00 -0800

It's been a tough couple of weeks for the U.S. Food and Drug Administration (FDA) and pharmaceutical companies. But it's also been difficult for the millions of people who are taking any of five medications cited as potentially dangerous at a Nov. 18 Senate hearing.

That hearing was held to explore the FDA's record on warning people about drug risks. During his testimony, David J. Graham, associate director of the FDA's office of drug safety, said underpublicized safety risks of five drugs weight loss medication Meridia; acne drug Accutane; asthma medication Serevent; cholesterol drug Crestor; and painkiller Bextra could lead to restrictions or withdrawal of the drugs from the market.

More than 15 million prescriptions were filled for the five drugs during the first nine months of this year, according to IMS Health, a pharmaceutical information and health care consulting company. While the makers rigorously defend the drugs' safety when taken as directed, some people who take them are scared.

Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland Medical Center in Baltimore, said at least 10 patients have called asking what to do. While some research suggests that Crestor carries greater risk of serious side effects than other statins, Miller said current knowledge does not warrant taking most patients off the drug. He will continue to monitor patients carefully and won't prescribe Crestor to those at high risk for the most serious side effects.

If you are taking one of these drugs and want to consider another treatment, experts recommend consulting with your doctor before stopping or changing any regimen. Some drugs interact with others, so you should tell your doctor about any drugs -- prescription or over-the-counter -- you're taking on a regular basis.

For those taking any of the five drugs, risks and options are discussed below.

Meridia Used for weight loss, works by "acting on the appetite control centers in the brain," according to its maker, Abbott Laboratories. The drug works best when combined with a low-calorie diet, the company says.

Risks Elevated risk of cardiovascular side effects, including heart attack and stroke.

Drugmaker Response Illinois-based Abbott says it stands behind the safety of the drug.

Alternatives The best way to drop pounds: Eat less, move more, doctors said. "I very much believe in behavior modification and lifestyle changes," said Tania Heller, medical director of Suburban Hospital's Center for Eating Disorders and Adolescent Obesity. For patients at high risk for complications of obesity -- such as those with type 2 diabetes -- drugs may help speed weight loss, Heller said. "But the key point to get across is not to rely only on medication" to lose weight, she said.

For patients who need medication, obesity drug Xenical, made by Roche Pharmaceuticals, is another option. The drug works by preventing about a third of the fat in the food you eat from being digested. Studies show that patients taking the drug lost twice as much weight as those on the same diet without medication. Side effects -- increased frequency and urgent need to empty the bowels, and gas with an oily discharge do not enhance its popularity.

Accutane A synthetic form of Vitamin A, used to treat severe acne.

Risks Can cause severe birth defects when taken by pregnant women.

Drugmaker Response The risk for birth defects when the drug is taken by pregnant women has been known since its 1982 approval, said Carolyn Glynn, spokeswoman for Roche Pharmaceuticals. Roche and the companies that distribute the three generic forms of Accutane require doctors to test women for pregnancy before prescribing the drug, and to sign forms stating they've educated patients about known risks.

Alternatives Oral antibiotics and topical medications should be tried before taking Accutane. But neither type of drug is considered as effective as Accutane in treating the most severe cases of acne, said Paula Bourelly, assistant professor of dermatology at Georgetown University Hospital. Since Accutane is the only medication considered effective for the most severe forms of acne, patients with the very worst cases have limited options. Bourelly said she has had new patients report taking antibiotics for months in an effort to clear up their acne.

Serevent A long-acting inhaled bronchodilator (a drug that widens the airways in the lungs) used for long-term management of asthma and chronic obstructive pulmonary disease.

Risks "Rare but serious asthma episodes and asthma-related fatalities occurred in a study with Serevent," GlaxoSmithKline reports on its Web site. "These risks may be greater in African Americans." Researchers think risks are higher for people with certain types of beta receptors (which exist on cells that line the surface of organs, including the lungs); this type of receptor seems more common in black patients. Some people of other races may have this type of beta receptor, too, doctors said.

Drugmaker Response GlaxoSmithKline says it addressed this concern by adding a "black box" to Serevent's label in August 2003, warning patients and doctors of this risk, according to a written statement the company issued on the day of Graham's testimony. Patients should not stop taking Serevent without their doctor's approval, the statement says.

Alternatives For those who don't want to take Serevent, there are several options, depending on the severity of the patient's asthma. Those with mild asthma may use a rescue medication like albuterol, which is taken only when the patient feels short of breath or has other asthmatic symptoms, said Martha White, an allergist at the Institute for Asthma and Allergy in Wheaton and Chevy Chase.

People with asthma who have symptoms at least twice a week need more treatment, White said. Options include another long-acting bronchodilator called Foradil, inhaled corticosteroids and Singulair, a leukotriene inhibitor (which is thought to work by blocking a substance that is released by cells in the lungs during asthma attacks).

Inhaled corticosteroids are considered the most effective at managing asthma symptoms, but they carry a heightened risk particularly at higher dosages of oral thrush (mouth infection), skin thinning and bruising with long-term use. The side effects for Foradil, usually used in combination with inhaled corticosteroids, include tremors, fast or irregular heartbeat, headache, muscle cramps or pain and, in rare cases, bronchospasms (narrowing of the airways). The side effects for Singulair which is not as effective as inhaled corticosteroids at controlling asthma symptoms include fatigue, fever, stomach pain and upset stomach.

Bextra A COX-2 painkiller often used to treat osteoarthritis.

Risks Bextra may have the same cardiovascular risks as those that caused Merck & Co. to pull Vioxx from the market in September. Some experts say that COX-2 drugs in general may be unsafe for long-term use. Existing research both confirms and refutes this risk, so more studies are needed.

Drugmaker Response Pfizer considers the drug to be "safe and effective," said spokeswoman Mariann Caprino. The drug company looks forward to the FDA's February 2005 meeting on the safety of Bextra and Celebrex, the only other COX-2 drug left on the market, Caprino said.

Alternatives Other choices include NSAIDs (nonsteroidal anti-inflammatory drugs), available by prescription (including Mobic and Daypro) and over-the-counter (including Motrin, Aleve and Advil).

Weight loss, if needed, and regular exercise may also ease pain. To relieve pain temporarily, heat and ice may help. Topical medications such as corticosteroids, Bengay and capsaicin may also ease soreness. Some patients may find relief through corticosteroid or hyaluronic acid injections into sore joints. Injection complications include infection, and repeated corticosteroid shots can increase risks of cataracts and bone weakening. In rare cases, skin whitens and thins at the injection site.

Crestor A statin drug used to treat high cholesterol.

Risks Kidney failure and rhabdomyolysis, a rare but potentially fatal muscle disease. Complications are more likely at higher doses (the highest approved dose in the United States is 20 milligrams; highest dosages elsewhere extend to 40 milligrams).

Drugmaker Response In a written statement issued Nov. 19, AstraZeneca said senior FDA officials reassured the firm that "there is no concern in relation to Crestor's safety and that they [the FDA] have issued a statement explaining that Dr. Graham's testimony does not reflect the views of the agency." The company has also run newspaper advertisements to reassure patients taking Crestor of the drug's safety.

Alternative treatments Other statin drugs include Lipitor, Zocor, Pravachol and Lescol. The decision on which to take should be made in consultation with your doctor, since dose and duration of treatment may vary depending on how high your cholesterol is, how low the target is and other factors. All statin drugs carry some risk for rhabdomyolysis, as well as risk of increasing liver enzymes. Liver function should be monitored regularly.

Diet and exercise are also powerful tools to help keep cholesterol and blood pressure in check, though doctors caution patients not to forego medication for levels deemed dangerously high by their doctors.

But don't stop taking your medication even if your cholesterol levels dip into safer territory. Former president Bill Clinton, who underwent emergency heart bypass surgery in September, had stopped taking his statin medication after losing weight and becoming more fit. His LDL or "bad" cholesterol level had decreased since his last presidential physical, from 177 to 114 when measured the week before his heart surgery. The recommended LDL level is less than 70.

Drugmaker Rebuffed Call To Monitor Users

Mon, 06 Dec 2004 00:00:00 -0800

The maker of Accutane, a controversial acne medication, disregarded a company doctor's recommendation that users of the drug be monitored for signs of depression and that a warning to that effect be added to the drug's U.S. label, allegations in a federal court case show.

The Florida lawsuit against the drugmaker, Hoffmann-La Roche, charges that the Swiss drug giant omitted the warning after its marketing officials argued that such an alert could cost the firm sales or prompt lawsuits. The doctor's recommendation and the marketing debate sketched in legal filings have not been previously publicized.

There has been no official finding that links Accutane to depression or other psychiatric illnesses. Roche says the drug is effective when used properly. Nonetheless, a senior Roche official, testifying in a pretrial deposition for the Florida case, said the firm's internal analysis showed Accutane "probably caused" depression and other psychiatric illnesses in some patients, according to a summary of the deposition in a court brief.

The internal debate alleged in the case comes to light after a U.S. Food and Drug Administration researcher last month told a Senate panel Accutane was one of five drugs that should be studied for possible withdrawal from the market. The FDA has since moved to tighten safeguards against the major side effect: birth defects in children whose mothers took Accutane while pregnant.

The alleged internal corporate debate over an Accutane warning, which emerged from a USA TODAY review of Accutane lawsuits, also comes as the recent withdrawal of another drug, Merck's pain reliever Vioxx, has intensified scrutiny of both drug companies and the FDA's oversight of the industry.

Accutane made its U.S. debut in 1982 as a prescription drug that provided relief to many who have a severe form of acne that fails to respond to other treatments. Although still widely used, the drug has been the focus of more than 20 years of medical and regulatory controversy.

Roche is a target of about 70 lawsuits for alleged adverse reactions that include suicides, depression, birth defects and gastrointestinal injuries.

Among those lawsuits is the Florida case filed by relatives of Charles Bishop, a 15-year-old who committed suicide in 2002 by stealing a small plane and crashing it into a Tampa skyscraper. His family alleges that Accutane, which Bishop began taking for acne eight months before he died, was responsible.

Similarly, Debbie Banner, a 33-year-old Virginia mother of two, contends the drug nearly incapacitated her with depression and caused severe birth defects in her first child.

And the family of Amanda Callais, 21, alleges in a New Jersey lawsuit that Accutane triggered the depression that caused the young Louisiana woman to try to commit suicide in 1997.

Higher rates of depression

Court records filed in the Bishop case show that Martin Huber, Roche's global head of drug safety, answered questions about reports of Accutane psychiatric effects as he testified in a pretrial deposition. Huber said the company's internal assessments showed Accutane "probably caused" depression and other psychiatric ailments in some users, according to the court file summary of his deposition.

The FDA and Roche consultants had told company officials the rate of depression among Accutane users was 1.5 times higher than among non-users, the summary shows Huber testified.

Daniel Zabrowski, Roche's global head of drug regulatory affairs, testified separately that Peter Schifferdecker, a company doctor based at the Basel, Switzerland, headquarters, in 1997 studied data on depression and other adverse psychiatric events reported by Accutane patients.

A summary of Zabrowski's deposition testimony filed in a court brief shows that Schifferdecker wrote a report that recommended changes in the drug's U.S. label and core data sheet the internal company document used by Roche to ensure consistency of the firm's products worldwide.

According to legal summaries of depositions by Zabrowski and other Roche officials, Schifferdecker recommended that Accutane's U.S. label warn that users "should be supervised for signs of depression during therapy and, if necessary, referred for appropriate treatment."

Warning label fears?

The company modified the core data sheet to reflect Schifferdecker's recommendation, records in the Bishop case state. But Zabrowski testified Roche's marketing division feared that placing the monitoring warning on the drug's U.S. label could hurt Accutane sales, the summary of his deposition shows.

Ulf Wiegand and John McLane, medical consultants in the marketing department, revised Schifferdecker's report to remove the reference to monitoring, and the firm sent the edited report to the FDA, Zabrowski testified, according to the summary of his deposition. The FDA declined to comment.

Records in the Bishop case also show that Angela Bylancik, another marketing staffer, wrote an e-mail stating that any decision "to add the proposed label change" should not be finalized "without full consideration of the enhancements to Dr. Schifferdecker's report."

"It is important to the International Dermatology Marketing Team that the change not be made to the core data sheet without full consideration of all available data and the potential impact on marketing strategy and product liability," Bylancik also wrote in the e-mail, which was included in the Bishop case court files.

Michael Ryan, a Fort Lauderdale attorney who is co-lead counsel coordinating that lawsuit and other Accutane cases filed against Roche in federal and state courts, said in telephone interviews the Bishop case filings showed that "the company put profits over safety."

In 1998, the FDA announced that Accutane packaging would be changed to warn that adverse reactions reported by some users included "depression, psychosis, and, rarely, suicidal ideation, suicide attempts and suicide." Roche sent alert letters to doctors advising of the change and telling them to monitor patients for any unexpected emotional shifts. But the FDA-prompted change, added to Accutane's label in 2000, was unrelated to Schifferdecker's monitoring recommendation.

Ryan argues that the exclusion serves as silent evidence that Roche's marketing division trumped the company's drug safety experts. "There is no good reason why that recommendation wasn't followed, other than profits," the attorney said.

Carolyn Glynn, a senior U.S. spokeswoman for Roche, said she could not comment on the matter because the company does not discuss pending litigation. Glynn, however, said Roche maintains "there is no causal relationship" that links Accutane to depression or other psychiatric illnesses.

In separate comments on Nov. 18, the day that FDA researcher David Graham told the Senate Finance Committee Accutane should be studied for possible withdrawal from the market, other Roche representatives said the drug was beneficial when used appropriately.

Long history of controversy

Despite those assurances, Accutane's record of controversy is even broader than the drug's extended warning label:

In 1986, four years after Accutane's U.S. debut, Roche changed the drug's package insert for doctors to advise that some patients had reported depression. An FDA memo of a 1994 telephone conference with Roche showed the firm had reviewed reports of suicide and depression related to Accutane and had "concurred that there does appear to be a problem."

Drug regulators in France required Roche to add suicide as a potential side effect to Accutane labels there in 1997. The FDA, which only learned of the action months later, reached its agreement with Roche on a similar label advisory in February 1998. Days later, the FDA sent Roche a warning letter over what regulators called "false or misleading" promotional material that suggested Accutane treated "psychosocial trauma" and "emotional suffering" associated with acne.

Janet Woodcock, director of the FDA Center for Drug Evaluation and Research, told a House subcommittee in 2002 that the agency had received reports of 3,104 adverse psychiatric events involving Accutane. She said the FDA at the time knew of 173 suicide reports associated with Accutane.

In 1988, Godfrey Oakley, director of the Division of Birth Defects and Developmental Disabilities at the Centers for Disease Control, wrote that "40 infants born alive after first trimester exposure to Accutane have died because of the developmental errors that Accutane caused." Oakley argued that "we simply need to remove the drug from the market."

In 1990, more than 14 years before his recent Senate testimony, Graham wrote that Accutane "cannot safely be given to women of childbearing age or potential" because the drug causes birth defects and results in abortions among women unwilling to give birth to children with deformities.

Graham, who calculated separately that the risk of severe adverse reactions from Accutane was roughly 3 per 100, "one to two orders of magnitude greater" than other drugs, concluded: "There is no alternative to immediate withdrawal of Accutane from the market. To delay only compounds the body count."

An attorney collaborating with Ryan on multiple Accutane lawsuits filed against Roche, said many of the cases allege the drug caused gastrointestinal illnesses. Accutane's label warns that the drug "has been associated with inflammatory bowel disease in patients without a prior history of intestinal disorders."

Adam Mason, a 28-year-old Florida resident unable to return to work as a welder since surgeons removed most of his colon to treat inflammatory bowel disease. In an interview last week, Mason said he's convinced that Accutane caused his illness. "I'm angry about what I have to go through every day of my life because someone didn't do their research properly," he said.

Motivated by concern about birth defects and other medical problems reported with Accutane, Public Citizen, a national consumer advocacy group, petitioned the FDA in 1988 for a ban on the drug. But the agency did not grant the petition or act on the recommendations that Accutane be pulled.

Instead, the FDA over several years considered establishing a mandatory registry for doctors who prescribe Accutane, pharmacists who dispense the drug and patients who take it. The registry proposal was aimed at strengthening efforts to keep pregnant women from taking Accutane. Regulators also considered using the registry for adverse psychiatric problems associated with the drug.

The FDA didn't take final action until last month, when it announced formal plans for an Accutane pregnancy registry. Under the move, a negative pregnancy test will be a prerequisite for a woman who's prescribed the drug. Refills will require a new pregnancy test.

Internal Roche documents uncovered by congressional investigators for the 2002 House subcommittee hearing show the company officials listed the absence of immediate FDA action on the proposed Accutane registry on an internal list of corporate "successes."

Other records found by the investigators include an October 2001 e-mail written by Cynthia Dinella, a Roche vice president of drug regulatory affairs. The message, addressed to Roche U.S. CEO George Abercrombie and other company officials, said the firm should "CELEBRATE" the FDA's non-action at the time. Noting that a registry might have "alienated" dermatologists who prescribe Accutane, Dinella wrote that "the outcome could have been drastically different" but for Roche's efforts.

Lawsuits claim tragic results

Debbie Banner says her life would have been drastically different if she hadn't taken Accutane.

A doctor prescribed it for the Virginia Beach resident in 1995, when Banner was a 24-year-old student at Old Dominion University and worked as a part-time aerobics instructor and coffee shop employee.

"From the beginning, I developed severe headaches and nausea," Banner said in an interview.

Within weeks, Banner said, she also found herself "constantly thinking about dying."

"Suicidal thoughts just came out of nowhere. It was very scary," she said.

A friend who noticed the behavior changes took her to a psychiatrist, who Banner said advised her to stop using the drug. Banner said her symptoms cleared up. But not before potential harm of the fetus she learned she was carrying the result of what Banner described as unprotected sex during Accutane-caused depression.

Banner said she rejected doctors who recommended an abortion. She said her son, now 8, was diagnosed with cerebral palsy and other severe defects at birth. Today, he requires a feeding tube to help with nutrition, suffers continuing seizures and bowel accidents and attends a special education program.

"He has a very difficult time doing anything for himself," Banner said. "He's going to need help all his life."

Banner and her husband sued Roche, but lost in a New Jersey court ruling that said Accutane's label adequately warned of the risks of taking the drug while pregnant. A state appeals court is weighing the case, in part on grounds that some internal Roche documents about Accutane weren't disclosed for the lower court proceeding.

Testifying at an FDA hearing this year, Banner detailed her son's injuries and urged the agency to impose tougher, mandatory safeguards to prevent pregnant women from taking Accutane.

In her words, "To leave this decision to patients who may be in denial and cannot protect themselves is to guarantee more birth defects and abortions."

Drug Makers Get Help With Accutane Safety

Wed, 24 Nov 2004 00:00:00 -0800

The manufacturer of the acne drug Accutane and companies producing generic versions of the medicine said yesterday they will step up efforts to reduce the risks of birth defects by borrowing from a system Celgene uses to restrict distribution of Thalomid.

The agreement comes less than a week after David Graham, a veteran scientist with the Food and Drug Administration, told a congressional committee that five drugs, including Accutane, may be too dangerous to keep on the market.

The deal allows Hoffmann-LaRoche, the maker of Accutane, and generic drug makers Barr Pharmaceuticals, Mylan Laboratories and Ranbaxy Laboratories to license the rights to Celgene's national registry for Thalomid. The companies did not disclose the financial details, but a spokesman for Celgene called the arrangements "modest."

Celgene, based in Warren Township, uses the registry to monitor physicians and pharmacists who prescribe and dispense Thalomid, Celgene's name for the notorious drug thalidomide.

Thalidomide was blamed for causing thousands of deformed babies in Europe and Canada during the 1950s and 1960s. In order to get regulatory approval to market the drug as a treatment for leprosy in 1998, Celgene was required to design a distribution system capable of preventing more birth defects.

Carolyn Glynn, a spokeswoman for Nutley-based Hoffmann-LaRoche, said the registry for Accutane, which is also known by its chemical name isotretinoin, is still being developed. In their announcement about the licensing agreement with Celgene, the companies also said they have hired Covance, of Princeton, to develop the registry.

Accutane was approved by federal regulators in 1982 to treat severe acne that did not respond to conventional treatments such as antibiotics. Under a physician's care, most patients remain on the drug for just five months.

Like Thalomid, Accutane poses a risk to pregnant women. The drug is blamed for causing 162 birth defects between 1982 and 2002, according to the March of Dimes. Nearly 2,000 pregnant women were exposed to the drug during that period.

During Accutane's 22-year history, Hoffmann-LaRoche has struggled with the drug's safety issues. The introduction of generic versions and the Internet, which creates a marketplace where consumers can obtain drugs without a prescription, have only heightened concerns over the drug's safety.

There are three generic versions of Accutane: claravis, amnesteem and sotret.

Hoffmann-LaRoche already requires female patients to get two pregnancy tests before they receive a prescription for Accutane. The registry would add another level of verification to ensure the existence of a lab-certified pregnancy test before a prescription is written.

"This is an enhancement of what we already have," Glynn said.

In 2002, Hoffmann-LaRoche created its own system to manage the risks of Accutane, and each of the generic drug makers was required to do the same. But critics have said the systems aren't working effectively to ensure that pregnant women don't receive the drug.

"We've always said that (Accutane) should be as restricted as Thalomid," said Michele Kling, a spokeswoman for the March of Dimes, which threatened to push for a ban on the drug. "This is a step forward."

In a statement yesterday, the FDA also said the registry should strengthen the systems already in place by Hoffmann-LaRoche and the generic drug makers.

"As stated in 2002, the goal of the agency was to eliminate fetal exposure to isotretinoin by ensuring that no woman start therapy if pregnant and no woman on isotretinoin therapy become pregnant," the FDA said in its statement. "This new program will go a long way to achieving this goal."

Concern About Drug Safety Doesn't Stop With Vioxx

Mon, 22 Nov 2004 00:00:00 -0800

Doctors have been taking calls from anxious patients ever since a Senate hearing on Vioxx last week at which an FDA scientist expressed concerns about the safety of five other drugs on the market.

That David Graham of the Food and Drug Administration's Office of Drug Safety named names was surprising. But to anyone who has kept up with the scientific literature and the drugs' evolving labels, the names themselves were not.

Steven Galson, an FDA administrator, attempted to temper Graham's testimony by saying the agency must consider benefits as well as risks, "so that safe and effective drugs remain available to patients who need them."

Some of what is known about the five drugs so far:

Accutane. Accutane can cause major fetal defects, and Roche, its maker, has warned against use during pregnancy since it came on the market in 1982. Yet, according to the March of Dimes, thousands of pregnant women have taken it.

In 2001, the FDA approved a voluntary system developed by Roche to prevent pregnant women from taking Accutane. But an FDA review found the proportion of Accutane users who were pregnant might actually have gone up in the year since the system went into effect.

In February, an FDA advisory panel recommended a more-restrictive program that would set up a registry of all Accutane prescribers, all pharmacists who dispense it and all users. It has not yet been implemented.

Bextra. As with Accutane, Graham did not call for Bextra in the same class of drugs as Vioxx to come off the market. But, he said, too little is known about Bextra's effect on heart attack or stroke risk. Last month, Pfizer sent a letter to health-care professionals mentioning results of two Bextra trials in heart-bypass-surgery patients. In both, the Bextra groups had more heart attacks and strokes than the placebo groups.

Crestor. This cholesterol drug has drawn regulators' attention in Europe and Canada.

At the Senate hearing, Graham said Crestor is the only statin drug that causes kidney failure. And, he said, it carries a higher risk of rhabdomyolysis than any other statin. Rhabdomyolysis is a potentially fatal muscle complication that benched another statin, Baycol, in 2001.

In June, Crestor maker AstraZeneca released a revised package insert for use in the European Union. It highlighted the rhabdomyolysis issue. Later that month, the Canadian government issued an advisory warning of a possible link between Crestor and rhabdomyolysis, especially at higher doses

Two months after the FDA approved Crestor in August 2003, consumer watchdog Public Citizen warned consumers not to use it because of kidney toxicity. The group has asked the FDA to ban Crestor.

Meridia. Graham said that few patients stay on the weight-loss drug very long because extended use can lead to increased blood pressure and stroke. Before Meridia was approved in 1997, an FDA advisory panel voted 5-4 that the drug's benefits did not outweigh its risks. Public Citizen has twice petitioned the FDA to pull it off the market.

Serevent. The Glaxo asthma drug, approved in 1994, dilates breathing passages. In 2003, its label began carrying a "black box" warning, the strongest type of warning, about the results of a large U.S. study that showed a small but significant increase in asthma-related deaths in patients who took Serevent. Advair, another Glaxo asthma treatment, which contains Serevent and a steroid, carries the same warning.

Richard Honsinger, a Los Alamos, N.M., asthma and allergy specialist, says he fielded some calls from worried patients after Graham's pronouncement. He says Serevent only relieves symptoms and should be taken along with a steroid to prevent permanent scarring in the lungs from inflammation.

Medical Experts Weigh Safety In Using Five Drugs

Fri, 19 Nov 2004 00:00:00 -0800

A day after an FDA official raised safety concerns about five widely prescribed medicines, doctors and patients had the same question: Should they still use the drugs?

David Graham, the Food and Drug Administration's associate director of drug safety, testified before a Senate committee Thursday that not only had his agency not given enough weight to safety concerns about the recalled painkiller Vioxx, but he also said regulators should be looking closely at five other drugs.

They are: Pfizer Inc.'s Bextra, a pain reliever in the same class as Vioxx; Crestor, a cholesterol-lowering drug manufactured by AstraZeneca PLC; Meridia, a weight-loss drug made by Abbott Laboratories; the acne drug Accutane made by Roche Holding AG; and Serevent, an asthma medicine from GlaxoSmithKline PLC.

Manufacturers of these drugs on Thursday defended their products, most of which already have the U.S. regulatory agency's "black box" warnings the strongest alert on their labels regarding safety issues. The five drugs Graham said warrant closer scrutiny have been approved as safe and effective by the FDA and "continue to be closely monitored with regard to safety and the balance of benefit to risk," FDA spokeswoman Kathleen Quinn said Friday.

Medical experts say patients taking those medications should not stop doing so without consulting with their physicians. Still, each of the medicines Graham criticized has been controversial. Here is why:

Bextra, in the same chemical class as Vioxx, was shown in a recent preliminary study to double the risk of heart attack and stroke among patients with heart disease, researchers reported at the annual meeting of the American Heart Association. Pfizer had already told regulators it intends to add to Bextra's packaging a black box warning that Bextra can cause potentially fatal skin reactions.

Crestor, a cholesterol medicine, has been linked to kidney failure and potentially life-threatening muscle damage. The consumer advocacy group Public Citizen asked the FDA in August to investigate AstraZeneca, alleging the drugmaker delayed reporting 23 cases of serious side effects. They included 19 cases of muscle weakening or rhabdomyolysis and four incidents of kidney damage.

Serevent, an asthma treatment, carries a boxed warning of a "small but significant increased risk" in asthma-related deaths in patients receiving the drug. The FDA said there were 13 deaths out of 13,174 patients treated for 28 weeks, versus four on placebo. The analysis also suggested the risk may be greater in black patients than Caucasians.

Meridia, an anti-obesity drug, increases blood pressure and heart rates and has been associated with a number of deaths and adverse reactions since it was introduced.

Accutane, an acne drug, can cause brain and heart defects, mental retardation and other abnormalities in babies of pregnant women taking the drug. Roche Holding and generic makers in February started a national registry mandating women cannot get their monthly supply of Accutane without a negative pregnancy test. They are told to use two forms of contraception while taking the drug.

Spokespersons for the five drugs' makers have said they are safe and effective when used as directed.

Public Citizen, founded by Ralph Nader, has asked the FDA to remove Crestor and Meridia from the market. Sidney M. Wolfe, the director of Public Citizen's Health Research Group, said Friday he also thinks Bextra should be pulled from the market.

"All these drugs are very problematic," Wolfe said. He added when people in the FDA like Graham raise questions, "their views are usually squelched. The FDA is too beholden to the manufacturers."

The problems "are generally known within the FDA, but the agency silences people who criticize the drugs or the policies," he said.

Daniel A. Hussar, a professor of pharmacy at University of the Sciences in Philadelphia, said Bextra was the only drug of the five Graham mentioned he thinks should be removed from the market. He said studies have indicated an increased risk of heart attacks and an association with a rare, but potentially fatal, skin reaction.

However, consumers should not be "unnecessarily alarmed" about health risks, he said. "Physician offices have to be overwhelmed with calls, but I think the alarm is excessive. When the drugs are appropriately used, and in appropriate doses, they can be safe."

Pfizer spokeswoman Mariann Caprino said her company is "committed to conducting long-term studies of Bextra" to detect possible problems.

AstraZeneca, maker of Crestor, said it remains "fully confident" the drug is safe. "We have been assured by the highest levels at the FDA that there are no new concerns about Crestor's safety and that Dr. Graham's testimony does not reflect the views of the FDA," said spokesman Steve Lampert.

Laureen Cassidy, a spokeswoman for Abbott Laboratories, said: "Science continues to support the safe use of Meridia to treat obesity, the leading health epidemic in the U.S. Meridia has been extensively studied in more than 100 clinical trials involving more than 12,000 patients throughout the world."

GlaxoSmithKline said Serevent "is safe and effective when used appropriately" and according to labeling guidelines, and it has a "black box" warning on its label.

LaRoche Holdings spokeswoman Carolyn Glynn said Accutane is reserved for "the most serious forms of acne unresponsive to other therapies."

The company and other generic manufacturers have a new national registry to monitor Accutane prescriptions. "This is something we have been very focused on for 23-plus years. It was a surprise to us that we ended up as one of the five drugs," she said.

Isotretinoin and Pregnancy - A Continued Risk for Birth Defects

Mon, 01 Nov 2004 00:00:00 -0800

n September 1982, the US Food and Drug Administration (FDA) approved the drug isotretinoin (Accutane) for use in the treatment of severe recalcitrant nodular acne. Accutane, taken orally over 20 weeks, was shown to be highly effective in treating this serious form of acne. However, within a year and a half of its approval, 29 cases of "adverse reproductive outcomes among women taking isotretinoin during the first trimester of pregnancy" were reported in the Morbidity and Mortality Weekly Report (MMWR).[1] Of the 34 exposed women reported, 19 experienced spontaneous miscarriage, and 10 babies were born with congenital malformations now understood to be the fetal isotretinoin syndrome.

Smith's Recognizable Patterns of Human Malformation[2] reports that retinoic acid embryopathy, also known as Accutane embryopathy or fetal isotretinoin syndrome, consists of a set of malformations involving the central nervous system, head and face, and heart. Isotretinoin (13-cis-retinoic acid) is a synthetic retinoid or vitamin A derivative. The retinoids are involved in the HOX signaling pathways that are used to pattern the branchial arches (pharyngeal arches) during the fourth week of embryonic development. It is not surprising, therefore, that the derivatives of the pharyngeal arches are affected by isotretinoin exposure during pregnancy, namely the central nervous system (CNS), craniofacial features, and cardiac structures.

Children with the isotretinoin syndrome often demonstrate facial asymmetry; serious external ear abnormalities, including microtia (small ear), anotia (no ear), or stenosis of the external ear canal; micrognathia (small jaw); flat depressed nasal bridge; and ocular hypertelorism (widely spaced eyes). The cardiovascular abnormalities commonly seen include conotruncal malformations, such as transposition of the great vessels and tetralogy of Fallot. Effects on the CNS can lead to hydrocephalus and microcephaly as well as to an IQ in the subnormal range and learning disabilities. Thymic aplasia and parathyroid abnormalities can also be part of this syndrome.

In 1988, a manufacturer-sponsored program called the pregnancy prevention program (PPP) was put in place to prevent birth defects from the use of Accutane.[3] The program provided educational materials for physicians and patients and also facilitated contraceptive use for women on Accutane by reimbursing for the contraceptive counseling. Also as part of the PPP, women who were taking isotretinoin were asked to enroll in the Boston University Accutane Study (BUAS). Enrollment was voluntary and the BUAS estimated that about 40% of women taking isotretinoin enrolled. Over the course of the study period, 1989 to October 1999, approximately 500,000 women enrolled. Among that group there were 958 pregnancies. A large proportion of the pregnancies, 834, ended in termination (either elective, spontaneous, or due to ectopic pregnancies), 110 resulted in live births, and 14 had unknown outcomes. Of the 60 infants with available medical records, 8 had congenital abnormalities.[4]

Concerns about exposure to isotretinoin during pregnancy continued through the late 1990s and into 2000. Roche, the manufacturer of Accutane, began a second program called SMART (The System to Manage Accutane Related Teratogenicity) in 2002. SMART includes patient information and labeling materials (booklets, video, and medication guide), consent forms, and yellow qualification stickers that providers need to affix to prescriptions indicating that patients have met all criteria for receiving Accutane prescriptions.

The guidelines for Accutane usage are as follows:

1. Isotretinoin is teratogenic, causes birth defects, and is Category X, meaning that there is no indication for its usage during pregnancy. In addition, it should not be taken while nursing.

2. Patients should take 2 pregnancy tests before starting isotretinoin and take a monthly pregnancy test while on the medication.

3. Two forms of birth control should be used starting 1 month before treatment, during the entire course of treatment, and for 1 month after ceasing treatment with isotretinoin. Even if one of the forms of contraception is hormonal, a second form should be used.

4. Providers should be knowledgeable about the use of isotretinoin and should read the educational materials and sign a letter of understanding before prescribing the medication. Yellow stickers are given to providers to affix to the prescriptions for isotretinoin. The yellow sticker indicates that the patient has met all criteria for receiving the medication, signed informed consent, and followed the pregnancy testing recommendations.

5. Pharmacists should dispense isotretinoin only when the yellow sticker is affixed to the prescription. Only a 30-day supply of medication should be dispensed at a time, to remind patients to take a pregnancy test monthly, before getting another 30-day supply.

6. Providers and consumers should realize that isotretinoin is a potent drug with the potential to cause birth defects and reserve its use for severe recalcitrant nodular acne. Isotretinoin is not for use in mild forms of acne and should not be shared among family members. Isotretinoin should not be purchased over the Internet without appropriate education and safeguards.

The SMART program continues to be a voluntary program and, unfortunately, pregnancies continue to be exposed to and affected by isotretinoin, an entirely preventable cause of birth defects. The March of Dimes has called for tighter controls on the use of Accutane and other recently available generic forms of isotretinoin. Early in 2004, March of Dimes urged the FDA to mandate a single, stringently monitored and restricted program for isotretinoin, such as the highly effective system created for thalidomide when it was licensed in 1998. Such a system would require provider registration and monitoring of prescriptions. Rather than simply being voluntary recommendations, many of the same safeguards around pregnancy testing and contraceptive use would be mandatory.

Most recently, there have been concerns that isotretinoin might be linked to depression and suicide in both men and women, adding to the list of potentially devastating consequences of isotretinoin. Congressman Bart Stupak, from Michigan's First Congressional District, has a keen personal interest in this issue because of his son's suicide while on the medication isotretinoin. He has advocated strongly for tighter regulation of isotretinoin (see http://www.house.gov/stupak/accutane.htm).

In conclusion, isotretinoin is a serious and powerful drug and should be used with great caution (see Table). Women in their reproductive years might well be concerned about their complexions and might desire isotretinoin for the potential improvement they might experience on their skin. Clinicians must keep in mind that approximately 50% of pregnancies in this country are unplanned, and therefore isotretinoin should be used with extreme caution so as to avoid inadvertent exposure and the occurrence of birth defects.

Stupak Pressures FDA To Act On Acne Drug Accutane

Fri, 08 Oct 2004 00:00:00 -0700

The Food and Drug Administration is facing renewed pressure from U.S. Rep. Bart Stupak and other lawmakers to require that patients receiving the acne drug Accutane, health workers who prescribe it and drugstores that dispense it enroll in a national registry.

Four lawmakers including Stupak, D-Menominee, whose teenage son committed suicide while taking Accutane, threatened on Thursday to seek legislation enacting the changes if the FDA fails to act by Nov. 1.

The FDA should "pull this drug until we have more research on the effects of Accutane and the permanency of those effects'' on children, the lawmakers wrote Wednesday in a letter to Health and Human Services Secretary Tommy Thompson. It was signed by Stupak, Sen. Gordon Smith, R-Ore., and Reps. Christopher Smith, R-N.J., and Dave Weldon, R-Fla.

Thompson oversees the FDA, which Stupak says has been slow to adopt recommendations from its own advisory committees on the matter. Federal advisers had called for such measures as pregnancy tests for women receiving Accutane and a caution to use two forms of contraception, to avoid birth defects associated with the drug.

Kathleen K. Quinn, an FDA spokeswoman, said Thursday the agency was preparing its response.

The lawmakers seek mandatory tracking of psychiatric events associated with the drug's use, including depression and heightened suicidal thoughts and behaviors, and they want to curb off-label prescriptions responsible for the bulk of Accutane use.

FDA Pressured To Act On Acne Drug Accutane

Thu, 07 Oct 2004 00:00:00 -0700

The Food and Drug Administration is facing renewed pressure from lawmakers to require that patients receiving the acne drug Accutane, health workers who prescribe it and drugstores that dispense it enroll in a national registry.

Four lawmakers including Rep. Bart Stupak, D-Mich., whose teenage son committed suicide while taking Accutane, threatened on Thursday to seek legislation enacting the changes if the FDA fails to act by Nov. 1.

The FDA should "pull this drug until we have more research on the effects of Accutane and the permanency of those effects" on children, the lawmakers wrote Wednesday in a letter to Health and Human Services Secretary Tommy Thompson. It was signed by Stupak, Sen. Gordon Smith, R-Ore., and Reps. Christopher Smith, R-N.J., and Dave Weldon, R-Fla.

Thompson oversees the FDA, which Stupak says has been slow to adopt recommendations from its own advisory committees on the matter. Federal advisers had called for such measures as pregnancy tests for women receiving Accutane and a caution to use two forms of contraception, to avoid birth defects associated with the drug.

Kathleen K. Quinn, an FDA spokeswoman, said Thursday the agency was preparing its response.

The lawmakers seek mandatory tracking of psychiatric events associated with the drug's use, including depression and heightened suicidal thoughts and behaviors, and they want to curb off-label prescriptions responsible for the bulk of Accutane use.

Suicide By Kids Sparks Hearing

Thu, 05 Aug 2004 00:00:00 -0700

Doctors told Dominique Slater's parents that their teenage daughter might become nauseated or gain weight from pills prescribed to battle depression.

But the 14-year-old Newman girl became irritable, hostile and aggressive side effects of anti-depressant drugs that her parents now say led to her suicide.

After Dominique's body was found April 14, 2003, in the Delta Mendota Canal in Patterson, her family was motivated to raise awareness about the potentially lethal link between anti-depressant drugs and teen suicide.

"Our obligation is to speak out so another family doesn't have to go through this nightmare," Lorraine Slater, Dominique's mother, said before a hearing Wednesday at the state Capitol.

She also testified before a federal Food and Drug Administration hearing in February. A month later, the FDA issued a warning that 10 anti-depressant drugs might worsen depression or suicidal tendencies. Dominique had taken three of the 10 drugs cited in the advisory.

Wednesday, as Dominique's brother Jonathan, 14, held framed family photos, her father, Robert, said anti-depressant drugs have not been proven safe for adolescents, who are being used as a "test market."

"I'm focusing on what we can do to avoid tragedies," said Sen. Tom Torlakson, D-Antioch, who called for the hearing before the Senate Health and Human Services Committee. His 21-year-old niece committed suicide earlier this year shortly after taking an anti-depressant drug.

"The FDA's warning came out a week after her suicide," Torlakson said.

Although England in December effectively banned six of the same drugs from use by children, no one on the panel Wednesday called for a similar ban, instead focusing efforts on more research to find out short-term and long-term effects of the drugs.

There also is a push to require patients to sign a waiver that explains the potential side effects, something already done for the drug Accutane, used to treat acne but linked to causing depression among teens.

"Family doctors now write 70 percent of prescriptions for anti-depressants and know little or nothing about this side effect," said Dr. Joseph Glenmullen, clinical instructor at Harvard Medical School and author of "Prozac Backlash," who spoke at the hearing.

He said doctors mistakenly think depression is getting worse and increase the dosage of the drug, possibly doing more damage.

Glenmullen added that drug companies have been dishonest about their research. He compared the industry with Big Tobacco, which he said spent years denying side effects, discrediting doctors, funding "junk science" by industry-friendly doctors and blocking needed research.

In June, New York Attorney General Elliot Spitzer filed a lawsuit against GlaxoSmithKline, maker of the anti-depressant Paxil, for concealing unpublished data.

The company had denied the charge.

In July, GlaxoSmithKline sent a letter to doctors advising that the drug not be used to treat children because of a "possible risk of suicide." In August, the maker of Effexor, Wyeth, sent a similar letter to physicians.

Drug company representatives were not included at Wednesday's hearing. But Carlo Michelotti, chief executive officer of the California Pharmacists' Association, told lawmakers that anti-depressant drugs are growing in popularity "because they work."

Stupak Proposes Accutane Limits

Wed, 16 Jun 2004 00:00:00 -0700

U.S. Rep. Bart Stupak, whose teenage son committed suicide in 2000 while taking Accutane, will introduce legislation today to tighten control over the controversial acne drug.

Stupak, D-Menominee, wants to require patients to sign a consent form that details risks, without which doctors and pharmacists couldn't prescribe and dispense it. He also wants a mandatory registry of users, prescribers and dispensers of the drug, which is known to cause birth defects when taken by pregnant women.

Stupak and other critics also charge that the drug can prompt users to commit suicide. Drugmaker Hoffmann-La Roche Inc. disputes the alleged link to severe depression and suicide, although the company alerts users to such possible psychiatric reactions in its product insert.

We are waiting for the (Food and Drug Administration) and Roche to come up with a final agreement (on tighter controls). That could take forever, Stupak said in explaining why he is introducing the bill.

In the wake of his son's suicide, Stupak has called for the drug to be banned. His wife, Laurie, is among users and surviving family members who are suing Roche, claiming the acne drug caused debilitating depression or suicide.

While the first suicide by an Accutane user was reported two years after the drug went on the market in 1982, it wasn't until the suicide of Stupak's 17-year-old son that worldwide attention focused on drug. B.J. Stupak was the president-elect of the student council at Menominee High School when he shot himself during a sleep- over party at his family home.

Roche spokeswoman Carolyn Glynn said the company and three generic manufacturers of Accutane are working with the FDA to implement a mandatory consent form and registry.

All of these things have been on the label, Glynn said. The difference is in linking in a mandatory way the patient, the physician and the pharmacist. We are going to connect all the players to leave no room for error. I have no concern that this won't happen.

Stupak is also calling for men to be warned that their use of the drug may cause birth defects. Roche maintains birth defects cannot be transmitted by male Accutane users.

Parents Sue Over Son's Suicide, Citing Acne Drug

Thu, 20 May 2004 00:00:00 -0700

The parents of a Springfield area teenager who killed himself after taking a powerful acne drug have filed a wrongful death lawsuit against PeaceHealth and the boy's dermatologist.

The suit, filed by the parents of Dustin Luke Greufe, seeks $1 million in noneconomic damages "for loss of love, society and companionship" and $1 million in economic damages, plus $5,000 for his funeral expenses.

The suit alleges PeaceHealth and Dr. Patricia O'Hare, a PeaceHealth Medical Group dermatologist, were negligent for inappropriately prescribing the drug Accutane to Dustin Greufe; failing to warn the Greufes of the drug's risks; and failing to monitor Dustin Greufe for adverse psychiatric side effects, including depression and suicidal thoughts.

PeaceHealth is the Bellevue, Wash.-based nonprofit corporate parent of Sacred Heart Medical Center and PeaceHealth Medical Group, a Eugene-based medical practice with about 110 physicians.

Greufe was a 16-year-old junior at Thurston High School when he hanged himself May 14, 2001, in the barn at his parent's home in Mohawk, northeast of Springfield.

A month earlier, he'd completed a six-month course of Accutane prescribed by O'Hare.

The drug, a synthetic derivative of Vitamin A, is powerfully effective at clearing up severe cases of acne. But it also has been linked to depression and suicide.

Since 1982, the U.S. Food and Drug Administration has received reports of 245 suicides, including 182 in the United States, associated with Accutane, agency spokeswoman Kathleen Quinn said Wednesday. The FDA says as few as 1 percent of "adverse events" associated with Accutane, such as suicide and attempted suicide, ever get reported.

Among the young people who have killed themselves after taking Accutane were the 17-year-old son of Michigan Congressman Bart Stupak, and Charles Bishop, a 15-year-old boy who flew a small plane into an office building in Tampa, Fla., four months after the Sept. 11 attacks. Bishop's mother is suing the drug's manufacturer, Swiss pharmaceutical giant Hoffman-La Roche.

Hoffman-La Roche representatives insist there's no scientific evidence that Accutane causes suicide and depression, but the FDA has required Roche to list both as potential side effects on the drug's label.

Colleen Greufe declined Wednesday to discuss the lawsuit or explain why she filed the suit herself, without benefit of a lawyer. In a 2001 interview, she and her husband said they believed Accutane was a factor in their son's suicide.

"I think it had a leading role," she said then. "He just had too many things going for him."

"To me there's no doubt," said his father, Matthew Greufe. "There's always going to be a doubt about how much it contributed, but there's no doubt it did."

Six months on Accutane cleared up the acne on Dustin Greufe's face, back and shoulders, according to his medical records, reviewed by The Register-Guard in 2001.

After each of his checkups, O'Hare noted in his chart that he had reported no problems with depression, mood swings, headaches, visual changes or stomach pain.

But his parents said he suffered some side effects, including nose bleeds, joint pain and severe stomach pain, his parents said. A nurse in O'Hare's office assured the family those were normal side effects.

Pregnant Women's Use of Accutane Results In Severe Birth Defects

Thu, 29 Apr 2004 00:00:00 -0700

Jennifer Morton chose abstinence as her form of birth control in order to start her prescription for Accutane. However, the drug's depressive side effects hit Morton (not her real name) hard, and after a few weeks of daily pills and crying spells, Morton fell to her lowest point.

"Everything went wrong that could have gone wrong with me, all in one little package," the 33-year-old mother said. "I had so many horrible side effects. It started with severe headaches, day and night nausea, but I'm thinking, this will go away, stick it out."

Then, in the midst of her depression, her old high school boyfriend convinced her to get back together. Morton said she was in too much of a mess to make any rational decisions and they hooked up.

Now Morton lovingly talks about her 7-year-old son David.

David has brain damage, seizures, speech problems, hand tremors, some autistic behavior, sensory impairment, chronic constipation and lack of muscle control. However, Morton said the hardest everyday task is worrying about David's feeding tube. The tube is needed because he can't work his muscles enough to even swallow water. David suffers from all of these problems because he is an Accutane-baby.

"It's just so hard," Morton said. "Everything is so hard. Some of the physical things he's caught up on, but he's so far behind."

Morton began taking Accutane when she was 24, and according to the FDA's Review of Pregnancy Reports, was right on target, as the largest group of Accutane patients, 27 percent, are women in the age range of 20-24.

Julia Robertson is the coordinator of the Utah Pregnancy Risk Line, a group interested in the increased number of Accutane-exposed pregnancies in Utah. In 2000, 13 pregnancies were exposed to Accutane, a drastic increase from the previous 15 years, where the average had been two or three. And despite the low number of pregnancies in 2003 -- five --it is still five too many for Robertson.

"We haven't seen a decrease in our numbers," she said. "We just got another patient this week. I don't know how to gauge that."

Robertson said in 2003, close to 200 Accutane-exposed pregnancies in the United States were reported to the FDA.

"That's too high," she said. "Our goal is in Utah to not have any pregnancies exposed."

Accutane, or the generic term, isotretinoin, is the strongest acne medicine on the market. It falls in the categories of teratogens, which have the potential to cause major deformities in a developing fetus. The drug is to be used only as a last resort after other acne treatments have failed.

Lynn Martinez, coordinator for the Birth Defects & Genetics Program in Utah worries that because Accutane is becoming a first-choice treatment, many patients are uneducated and don't understand how powerful the drug really is.

"The thing about Accutane that I think most folks don't know, is that it's the strongest known inducer of birth defects," she said. "It's the worst, not just in terms of medicines, but in terms of anything. It carries the highest risks for the worst conditions."

No longer just a teenage wonder drug, Accutane is becoming a hot commodity among women of childbearing age. Those who want to get rid of acne often use it as a quick fix, which shouldn't be happening, according to Roche, the company that created Accutane.

Before beginning the drug, patients should be examined by a family physician or a dermatologist to see if they have severe, scarring acne. Doctors should also explain the numerous possible side effects, and stress the importance of two forms of birth control for the duration of the prescription. Females must also take a pregnancy test before starting medication.

System to Manage Accutane Related Tertogenicity, or SMART, is Roche's educational system designed to prevent pregnancy by requiring participation for women who take Accutane and doctors who prescribe it. As part of the education, Gail Safian, a public affairs consultant for Roche, said the company distributes a spiral-bound book, not just a pamphlet, to help educate doctors and patients.

"We have a very major program actually," Safian said. "We've always had educational materials for the physicians and their patients."

Dermatologists and physicians are required to read this book and sign a letter saying they understand how to prescribe the drug. After this training, they are enrolled and receive special stickers that are placed on prescriptions to signify validity.

After patients review this booklet, they are given a three-page consent form that again specifies Accutane should only be used only as a last resort. It also reminds patients of the drug's numerous side effects, such as depression, tiredness, loss of appetite and possible suicidal thoughts. The form also requires the patient to tell doctors of any past or current symptoms of depression. There are 12 places for patients to initial their understanding, and multiple spaces for signatures from health care providers.

Robertson is aware of this program, but wonders about its efficacy, as it is impossible to know how much time doctors are setting aside to go over everything.

"If you look at the manufacturer's program, it's substantial," Robertson said. "But what we don't know is if health care providers are using it."

For Morton, the SMART program wasn't even around when she started taking the drug. She said she remembered the birth control issue as a quick question with little follow-up.

"She [the dermatologist] said, 'What form of birth control would you like to use?' and I chose abstinence," Morton said. "That was the end of our conversation on that. That was it-it was about a sentence long." The entire Accutane-acquiring process was just as forgettable.

"I did get a brochure," Morton said, "Nothing I kept. But basically I signed a consent form, but it was just 'Here, sign this, go.' It wasn't anything that I really knew at the time, or knew what I was getting myself into."

At a recent February conference in Maryland, the FDA, Roche and the Drug and Safety Advisory Committee met to discuss the SMART program and its failings. The FDA demanded that Roche put in place a mandatory registration for Accutane users that would put more pressure on doctors to record who is taking the drug and how they are doing. However, Robertson said it might take more than action on Roche's part to truly effect a change.

"If health care providers and their clients work together and follow those recommendations that are in the drug insert, we shouldn't have any pregnancies," she said. "But we're not following those, and until they are mandatory requirements, I don't think anybody will follow them. Roche can say, this is what you have to do, but Roche really doesn't have a lot of power to do that. The FDA has to come through and say it's a must."

Increased awareness may have helped Morton, as well as better education about side effects. She described her experience as horrible, as the side effects of Accutane took over her life. She said she thinks it might not have been so bad had she been more carefully monitored.

Besides the constant nausea and headaches, Morton later developed hypersomnia, a sleep disorder, and because she was so weak, forgetful and depressed, she was forced to quit school and her two jobs. She also developed suicidal thoughts and was taken to a psychiatrist.

BYU junior Derrick Allred, a biology major from Richfield, said he took Accutane for three months. His brothers and his mom also took the acne medication.

"There are definitely a lot of mood changes, attitude changes," he said. "My mom took it for the full six months, and it was six months of heck."

The Allreds may not have experienced psychiatric effects as severe as Morton's, but the occurrence of such symptoms is not unusual, nor surprising. In the 30-plus page Accutane manual, Roche lists side effects occurring in areas such as cardiovascular, endocrine, gastrointestinal, musculo-skeletal, neurological, psychiatric and respiratory, with side effects ranging from headache and insomnia to depression and stroke.

Morton said her biggest complaint is with the psychiatric influence of the drug. She points out that Roche warns about the psychiatric, as well as the terotegenic side effects, but said she thinks for safety reasons, the two effects shouldn't be together in one medication.

"You shouldn't be giving a teratogen to someone who could be in a severely depressed mental state, then requiring that they use two forms of birth control," Morton said. "[They're] underestimating what a responsibility that is. Throw in depression and suicidal thoughts, and you're just asking for it."

Accutane affected Morton to the point where she could no longer make rational decisions. Getting pregnant would have never happened if she hadn't been on Accutane, she said.

"It happened, and it was a mistake," she said. "At first I thought it was my fault and I was such a horrible person. How could I have ever let something like this happen? I learned later that the psychiatric side effects of Accutane were doing something to me that was out of my control."

For Morton, Accutane is no longer a simple aesthetic oral treatment, but a strong drug that is misunderstood and under-regulated. Morton said she wants in-depth pre-screening, more monitoring and better follow-up if Accutane is going to continue to be prescribed to women of childbearing age. She warned that even if someone is mentally healthy starting the drug, they still need to be followed by a psychiatrist, and if side effects like hers occur, they need to get professional help and stop the treatment before pregnancy becomes an issue.

"I believe there's an increased risk of unplanned pregnancies when a patient is exposed to psychiatric side effects," Morton said. "There's a huge increased risk."

The FDA conference was a big step in helping to address an issue that has forever changed Morton and David's life. Talking about her son is another step.

"It takes me a lot of guts to tell my story because I know people can really attack me and judge me," she said. "I know there are other girls going through this, so I want to say something because my child has birth defects. I don't think it's worth it to keep quiet. I really want to warn people, so it doesn't happen to them."

Survey on Acne Medications and Birth Defects Reinforces Need for Stricter Regulation and Education

Mon, 26 Apr 2004 00:00:00 -0700

Pregnancy and powerful acne medicines like Accutane don't mix. That's the message pregnancy counselors with the Organization of Teratology Information Services (OTIS) are trying to convey to pregnant women, health care providers, pharmaceutical companies, and decision-makers in the federal government.
Women who have used Accutane, known generically as isotretinoin, within 30 days of becoming pregnant are encouraged to participate in an ongoing OTIS study.

Callers will be given information on the potential effects of isotretinoin and be asked to take a brief survey about how much isotretinoin they were using when they became pregnant, how they obtained the drug, and what level of education they received when the drug was prescribed.

"Having nice-looking skin is not worth the risk of having an abnormal baby or child," stressed Debbie Banner, a Virginia mother whose son was born with brain damage as a result of Accutane exposure during her pregnancy.

The FDA approved Accutane in 1982 as a prescription medication for severe or cystic acne. Although the drug's label warned it was not to be taken by pregnant women, exposed pregnancies continued. It was found that Accutane was a teratogen, meaning it can cause brain and heart defects, mental retardation, and other abnormalities.

By 1999, it was reported that nearly three out of every 1,000 American women aged 15-44 were taking Accutane. The more recent introduction of additional forms of isotretinoin (Amnesteem, Claravis, and Sotret) may further increase usage.

In late February, the Food and Drug Administration (FDA) held hearings to consider imposing stricter regulations on Accutane, which has been shown to cause birth and developmental defects.

OTIS, a nonprofit organization that conducts research and provides education on the effects of drugs and chemicals on the human fetus, presented preliminary findings from a survey of women in the U.S. and Canada who used Accutane at the time they became pregnant. OTIS told FDA members that only the most stringent restrictions could prevent more Accutane-exposed pregnancies.

The FDA has agreed to review recommendations by an advisory panel for manufacturers to establish a national registry system in which all patients using any form of isotretinoin would be required to enroll. For female patients, this would mean they could no longer obtain a prescription without a negative pregnancy test and written instructions by their doctor to use two forms of birth control while on the drug.

"We encourage the manufacturers of isotretinoin to implement a mandatory, nationwide registry, including required contraception counseling by trained professionals," said Dr. John C. Carey of the University of Utah School of Medicine and Medical Director of Utah's Pregnancy Risk Line, which was instrumental in obtaining the grant for the OTIS survey.

The grant awarded by the Centers For Disease Control and Prevention has enabled OTIS and more than 20 other teratology information organizations across North America to gather critical data about exposure to Accutane and generic isotretinoin during pregnancy. The hope is the findings will be used in future decisions about drug regulation as well as to increase and expand pregnancy prevention education.

Defects Linked To Acne Drug May Bring Stiffer Restrictions

Sun, 28 Mar 2004 00:00:00 -0800

A prescription acne drug that has helped millions of Americans but has also been linked to serious birth defects soon may be much more difficult for consumers to obtain.

As of last week, federal regulators were still considering placing extraordinary restrictions on the drug, Accutane, which would require a woman seeking a prescription to provide evidence of a negative pregnancy test each month. She also would have to agree to use two forms of birth control to fill a prescription.

Also, to serve patients using Accutane, pharmacy workers and prescribing doctors would be required to enroll in a federal registry.

A Food and Drug Administration scientific advisory panel recommended the stringent restrictions late last month because previous, mostly voluntary safeguards have failed to sufficiently slow the number of birth defects among Accutane users.

But many dermatologists complain that the proposed registry and other safeguards would violate patients' privacy and make it difficult for some people to take the medication.

"It's going to be more work to take it," said Dr. Barbara Reed, a Denver dermatologist who represented the American Academy of Dermatology at a government hearing. "Patients may ask, 'How much trouble do I want to go through to get this drug?' "

Damning statistics

Accutane can cause limb and organ deformities and mental retardation. More than 160 babies have been born with defects blamed on the drug since it went on the market in 1982; hundreds of other women who have become pregnant on Accutane have had abortions, according to the FDA.

Accutane also is available in a generic form called isotretinoin.

The drug's toxicity during pregnancy has long been known, but previous efforts to reduce birth defects including stricter product labeling and a limited pregnancy testing system have failed to resolve the problem, according to data presented at the hearing.

"The program that has been in place has not been entirely successful," said Arthur Levin, director of the Center for Medical Consumers, a nonprofit consumer-advocacy organization in New York City that supports tighter restrictions. "We're not sure why."

Under the new regulations, initially proposed by the drug's manufacturer, Hoffmann-La Roche, women will have to agree to use two forms of birth control, one of which must be a "primary" form, such as the birth-control pill. Abstinence, however, would be considered one form of birth control, said Gail Safian, a spokeswoman for Hoffmann-La Roche. Monthly pregnancy tests would have to be performed by a certified lab home tests won't do and the results would have to be verified.

Might turn to Internet

But some speakers at the FDA panel hearing expressed concern that the restrictions might lead some patients to obtain Accutane on the Internet, without any medical supervision.

More than 1 million prescriptions for Accutane or its generic equivalent are written each year in the United States.

The drug, which is derived from vitamin A, is typically taken for at least five months. In most patients, it is highly successful in suppressing cystic acne a severe form of acne for long periods of time or even permanently. Most Accutane users have failed all other acne therapies and use the powerful drug as a last resort.

Despite its effectiveness, Accutane has been associated with other side effects, some serious. The drug is linked to an increased risk of depression and suicide.

Accutane also can cause elevated triglyceride levels, which can cause pancreatitis, and patients usually are required to undergo monthly blood tests to monitor triglyceride levels. Severe dryness of the lips, skin and mucous membranes is common when taking the medication.

Accutane prescriptions have fallen about 20 percent since 2001, and dermatologists say the proposed restrictions will cause more patients who could benefit from the drug to refuse a prescription.

"I think this will potentially have an impact in terms of making it a less desirable medication," said Dr. Steven Weiss, chief of dermatology at Cedars-Sinai Medical Center in Los Angeles. "But it's been a godsend to many patients."

Too much trouble?

If asked to enforce the stricter regulations, some doctors and pharmacists may decide to forgo offering the drug, said Reed.

Doctors already are required to register to prescribe Accutane, and more than 12,000 dermatologists have done so, according to Hoffmann-La Roche.

"I have heard from my acquaintances who say, 'I'm not going to do it; let someone else do it,' " Reed said. "Patients are going to have to find a doctor who will write the prescription and a pharmacy that will fill it."

How to enroll patients into the registry and honor new federal laws protecting patient privacy is another large hurdle, said Dr. Wilma Bergfeld, a dermatologist at the Cleveland Clinic and a member of the advisory panel. "How the FDA will work around that, I don't know," she said. "This is breaking new ground."

The FDA must still decide whether to adopt the advisory panel's recommendation. It's unclear how the regulations would be enforced. Men also would be enrolled in the registry in order to receive counseling about the importance of not sharing their pills with women.

Curbs Urged On Acne Drug

Mon, 08 Mar 2004 00:00:00 -0800

A prescription acne drug that has helped millions of Americans but has also been linked to serious birth defects soon may be much more difficult for consumers to obtain.

Federal regulators are considering placing extraordinary restrictions on the drug, Accutane, which would require a woman seeking a prescription to provide evidence of a negative pregnancy test each month. She also would have to agree to use two forms of birth control to get a prescription filled.

Also, patients using Accutane, pharmacy workers and prescribing doctors would be required to enroll in a federal registry.

A Food and Drug Administration scientific advisory panel recommended the stringent restrictions last month because previous, mostly voluntary safeguards have failed to sufficiently slow the number of birth defects among Accutane users.

But many dermatologists complained that the proposed registry and other safeguards would violate patients' privacy and make it difficult for some people to take the medication.

"It's going to be more work to take it," said Dr. Barbara Reed, a Denver dermatologist who represented the American Academy of Dermatology at a government hearing. "Patients may ask, 'How much trouble do I want to go through to get this drug?' "

Accutane can cause limb and organ deformities and mental retardation. More than 160 babies have been born with defects blamed on the drug since it went on the market in 1982; hundreds of other women who have become pregnant on Accutane have had abortions, according to the FDA.

Accutane also is available in a generic form called isotretinoin.

The drug's toxicity during pregnancy has long been known, but previous efforts to reduce birth defects including stricter product labeling and a limited pregnancy testing system have failed to resolve the problem, according to data presented at the hearing.

"The program that has been in place has not been entirely successful," said Arthur Levin, director of the Center for Medical Consumers, a nonprofit consumer advocacy organization in New York City that supports tighter restrictions. "We're not sure why."

Under the new regulations, initially proposed by the drug's manufacturer, Hoffmann-La Roche, women will have to agree to use two forms of birth control, one of which must be a "primary" form, such as the birth control pill. Abstinence, however, would be considered one form of birth control, said Gail Safian, a spokeswoman for Hoffmann-La Roche. Monthly pregnancy tests would have to be performed by a certified lab home tests won't do and the results would have to be verified.

But some speakers at the FDA panel hearing expressed concern that the restrictions might lead some patients to obtain Accutane on the Internet, without any medical supervision.

More than 1 million prescriptions for Accutane or its generic equivalent are written each year in the United States.

The drug, which is derived from vitamin A, is typically taken for at least five months. In most patients, it is highly successful in suppressing cystic acne a severe form of acne for long periods of time or even permanently. Most Accutane users have failed all other acne therapies and use the powerful drug as a last resort.

Despite its effectiveness, Accutane has been associated with other side effects, some serious. The drug is linked to an increased risk of depression and suicide.

Accutane also can cause elevated triglyceride levels, which can cause pancreatitis, and patients usually are required to undergo monthly blood tests to monitor triglyceride levels. Severe dryness of the lips, skin and mucous membranes is common when taking the medication.

Accutane prescriptions have fallen about 20% since 2001, and dermatologists say the proposed restrictions will cause more patients who could benefit from the drug to refuse a prescription.

"I think this will potentially have an impact in terms of making it a less desirable medication," said Dr. Steven Weiss, chief of dermatology at Cedars-Sinai Medical Center in Los Angeles. "But it's been a godsend to many patients."

If asked to enforce the stricter regulations, some doctors and pharmacists may decide to forgo offering the drug, said Reed, the Denver dermatologist.

Doctors already are required to register to prescribe Accutane, and more than 12,000 dermatologists have done so, according to Hoffmann-La Roche.

"I have heard from my acquaintances who say, 'I'm not going to do it; let someone else do it,' " Reed said. "Patients are going to have to find a doctor who will write the prescription and a pharmacy that will fill it."

That could become difficult in rural areas of the country, Reed adds.

How to enroll patients into the registry and honor new federal laws protecting patient privacy is another large hurdle, said Dr. Wilma Bergfeld, a dermatologist at the Cleveland Clinic and a member of the advisory panel. "How the FDA will work around that, I don't know," she said. "This is breaking new ground."

The FDA must decide whether to adopt the advisory panel's recommendation. It's unclear how the regulations would be enforced. Men also would be enrolled in the registry to receive counseling about the importance of not sharing their pills with women.

Drug Warning For Pregnant Women

Mon, 01 Mar 2004 00:00:00 -0800

Although it's an effective drug for acne, Accutane causes miscarriage and severe birth defects if taken by a woman who is pregnant. And the latest numbers show that Accutane pregnancies are still occurring despite recent efforts to counsel and educate users of the drug.

In a one-year period after safety measures were strengthened in 2002, 120 pregnancies were reported, compared with 127 during the year before when there were looser restrictions.

Now advisers to the Food and Drug Administration want a mandatory registry to track women who take the drug in an effort to make sure they are following the guidelines to prevent pregnancy, The Early Show medical correspondent Dr. Emily Senay reports.

Accutane is widely prescribed because it is a highly effective drug for the treatment of severe acne. It's also increasingly prescribed for less severe cases.

The drug has been called a silver bullet for acne because it tackles acne on several levels to clear it up.

It's usually prescribed for a five-month period and it's effective in about forty percent of cases.

Guidelines for taking Accutane:

There are some basic recommendations that need to be adhered to religiously to avoid pregnancy and the potential for miscarriage and birth defects.

First, before you start taking the pills, you need to have two negative results from a pregnancy test including one on the second day of the next normal menstrual cycle after the first test. You should also use two forms of effective birth control. You should have to repeat pregnancy tests every month while taking the drug.

Part of the problem is that not enough doctors make sure their patients understand the issues, and part of the problem may be that the patients do not follow the directions for using the drug.

The new registry would require women to produce a negative pregnancy test before getting prescriptions refilled, and require pharmacists to double-check that women are properly screened before handing over the pills.

The registry cannot make women comply with the contraception guidelines. It's impossible to control what patients do once the prescription has been filled.

Accutane is not for everybody, and it is not a first-choice therapy because in many cases you can have effective treatments without this risk.

FDA Debates More Restrictions on Accutane

Fri, 27 Feb 2004 00:00:00 -0800

Critics are calling for major new curbs on who can get a prescription for the acne drug Accutane, after voluntary restrictions failed to reduce the number of pregnancies among women using the birth defect-causing medicine.

The Food and Drug Administration is asking its scientific advisers what additional safeguards are needed to battle the birth-defect problem that Accutane has posed since it first hit the market in 1982.

One of those advisers charged the FDA missed a crucial opportunity for better safeguards three years ago - by ignoring this same panel's recommendation that Accutane be sold only to female patients enrolled in a national registry, with mandatory pregnancy testing.

Instead, the FDA opted for essentially voluntary restrictions, partly because of legal questions about patient privacy.

Failure of those restrictions means it's now time to make Accutane one of the nation's most restricted drugs by replacing routine sales with a special controlled-access program, said FDA panelist Dr. Curt Furberg of Wake Forest University.

"The history of Accutane is an example of inadequate and ineffective risk management by the FDA and the manufacturer of Accutane, to the detriment of thousands of women," wrote Furberg, who missed Thursday's meeting but sent a letter with his views to fellow advisers.

Acknowledging more protection is needed, Accutane maker Hoffman-La Roche Inc. and three generic manufacturers are proposing a somewhat stricter system that would allow the drug's use and distribution only by patients, doctors and pharmacists who are tracked on a national registry.

Going further, as Furberg and some other critics suggest, might encourage women to seek Accutane on the Internet without any medical supervision, said Roche spokeswoman Carolyn Glynn. "We're trying to find a balance."

The full advisory panel will issue recommendations Friday.

If a woman becomes pregnant while taking Accutane, her baby can suffer severe brain and heart defects, mental retardation and other abnormalities, even if the mother took only a small dose for a short period.

The FDA has well over 2,000 reports of women on Accutane becoming pregnant since 1982, when the drug began selling. The vast majority opted for abortion. While some healthy babies were born, the FDA counts more than 160 babies born with Accutane-caused birth defects in that time.

Warning after warning to doctors and patients didn't help, so in 2001 the FDA settled on some broad restrictions: Doctors were supposed to ensure female patients had two negative pregnancy tests and agreed to use two forms of contraception before prescribing Accutane. Pharmacists were supposed to fill only prescriptions bearing a special sticker certifying doctors had done that. Women could get a month's supply at a time, with refills dependent on another negative pregnancy test.

In the first year of those restrictions spring 2002 to spring 2003 the FDA counted 120 pregnancies among Accutane users, just seven fewer than in the year before the new program.

There's no way to know if the FDA counted all the pregnancies, since reporting them is voluntary; one critic suggests almost five times as many may have occurred.

Nor could the FDA track all the pregnancies. Of 29 known live births, the FDA attributed Accutane-caused birth defects to four.

At the same time, total prescriptions for Accutane and its generic version, called isotretinoin, dropped 23 percent, from 1.5 million to 1.16 million.

Part of the problem is overuse of Accutane, critics say. It is intended for people with very severe acne, the kind that causes large cysts and leaves deep scars, yet often is prescribed for mild acne.

Accutane Linked to Birth Defects, Should Be Pulled From Market, Public Citizen Tells FDA

Thu, 26 Feb 2004 00:00:00 -0800

The acne drug Accutane, which causes birth defects and life-threatening adverse events, should be removed from the market and prescribed only under very limited and controlled conditions, Public Citizen told a government panel today.

At a meeting of a U.S. Food and Drug Administration (FDA) advisory committee, Dr. Sidney Wolfe, director of Public Citizens Health Research Group, described how the drug causes such birth defects as malformations of the heart and brain, and can cause depression and create pressure in the brain in patients taking it. About 25 percent of the babies born to mothers taking the drug have serious birth defects and 50 percent are mentally disabled. Many women who become pregnant while taking the drug have abortions because of this high birth defect rate.

Accutane is approved only to treat severe cystic acne but is prescribed to many people who have mild acne. In fact, it is prescribed to 26 times more women than it should be, Wolfe estimates.

A program launched in April 2002 by the FDA and Accutanes manufacturer, Roche, was designed to reduce the number of pregnant women taking the drug, but it has not worked, Wolfe said. In the programs first year, 48 of 61 reported pregnancies (79 percent) ended in elective abortions because of concerns about the high rate of birth defects caused by the drug. Applied to the estimated number of total pregnancies in women taking Accutane during that year, an estimated 431 women had abortions because of the drugs high defect rate, 16 infants were born with birth defects and 31 babies were born with mental retardation. From 1982 to 2000, 162 babies were reported born with birth defects attributable to Accutane.

"If the government doesnt act, this administration and advisory committee will continue to put its imprimatur on the reckless use of a drug that each year causes the need for hundreds of abortions and results in many seriously deformed infants with birth defects," Wolfe said. "This is one of the two worst epidemics of preventable serious birth defects ever seen in the United States. It is time to end it."

Officials have known for at least 20 years of the dangers associated with the drug. In 1983, Public Citizen petitioned the FDA to give patients warning information with the drug. In 1988, Public Citizen petitioned for a ban on Accutane, but the agency didnt act. Public Citizen will petition the agency again soon for the drugs withdrawal, Wolfe said. Wolfe told officials today that the drug should be prescribed only if photographic proof exists of severe cystic acne and the patient has not responded to other acne treatments. In addition, for women, a written statement should detail the patients contraceptive practices and the patient should have a negative pregnancy test.

Accutane Causing Miscarriages, Major Birth Defects; Tighter Controls Urgently Needed, March of Dimes Says

Wed, 25 Feb 2004 00:00:00 -0800

Major birth defects caused by exposure to Accutane and other brands of isotretinoin, an acne therapy drug, continue to occur in the United States each year because of the failure of voluntary safety measures meant to prevent them, the March of Dimes says.

At an advisory committee meeting to be held tomorrow by the Food & Drug Administration, the March of Dimes will call on the agency to immediately impose tougher restrictions on isotretinoin modeled on the system put in place for thalidomide.

"No pregnant woman should ever take isotretinoin, and no woman taking isotretinoin should ever get pregnant," says Nancy S. Green, M.D., medical director of the March of Dimes. "However, there have been at least 2,000 exposed pregnancies reported since this drug was introduced, and this figure may be only the tip of the iceberg."

"FDA's own Center for Drug Evaluation and Research recently concluded that the newest version of voluntary safety measures by manufacturers have produced no substantial improvement in reported pregnancy exposures. The tragic consequence for families has been miscarriages, fetal loss, and major birth defects.

"The March of Dimes urges FDA to mandate a single, stringently monitored and restricted program for isotretinoin, such as the highly effective system created for thalidomide when it was licensed in 1998."

If such a system is not put into place, the March of Dimes may consider calling for a ban on all systemic forms of isotretinoin, Dr. Green says.

Dr. Green warns women of childbearing age with acne who may want to take isotretinoin to consult a physician qualified to advise on its proper use and avoid Internet suppliers. In addition, she says, those who have prescriptions for isotretinoin should never share this drug with others.

Dr. Green says there is a high risk of fetal malformations if a woman becomes pregnant while taking isotretinoin, even if she is taking a small amount of the drug for a short period. Birth defects associated with isotretinoin include hydrocephaly (enlargement of the fluid-filled spaces in the brain); microcephaly (small head and brain); mental retardation; heart defects; ear and eye abnormalities; cleft lip and palate; and other facial abnormalities.

"Isotretinoin can cause these birth defects in the early weeks after conception, a time when a woman often doesn't know she's pregnant," she says.

Isotretinoin is a member of a family of drugs called retinoids, which are related to vitamin A. Other retinoids include Soriatane (acitretin), Tegison (etretinate), and Vesanoid (tretinoin).

In a January 2000 issue of Morbidity and Mortality Weekly Report, the Boston University Accutane Survey (BUAS) reported that 900 women became pregnant while taking isotretinoin between 1989 and 1999, a rate of 3 women becoming pregnant for each 1000 treatments with the drug. Roche Laboratories, makers of Accutane, reported to FDA that, from 1982 to 2000, there were 1,995 pregnancy exposures and 383 live births, of which 162 had birth defects. FDA says there were 325 known pregnancies in users of isotretinoin between April 1, 2001 and August 15, 2003.

Teen Pilot's Kin Blame Drug For Suicide

Wed, 04 Feb 2004 00:00:00 -0800

Charles Bishop loved "Star Trek" and Tom Clancy novels. He worried about learning how to drive, and had only been on one date. He rarely mentioned the father he never knew, but learned a love of flying from his mother's best friend, a man he considered a father figure.

In volumes of recently filed court records, those are some of the ordinary details from the life of a 15-year-old boy that make an enduring mystery of why he stole a small airplane and crashed it into a Tampa skyscraper, leaving a suicide note sympathetic to Osama bin Laden.

His mother and grandmother have filed a $70 million lawsuit against the makers of the acne drug Accutane, blaming it for sparking his irrational act in January 2002.

The drug company denies Accutane is linked to suicide, but it does warn doctors and users to watch for suicidal behavior.

In hours of depositions, Bishop's mother, grandmother and the dermatologist who prescribed him Accutane about eight months before Bishop's death said they saw no indications of impending suicide.

His doctor testified he was so vigilant in watching for signs of depression and aggression that he once called the boy's mother, Julia Bishop, because he'd overheard a minor argument between Charles and his grandmother.

Grandmother Karen Johnson said they too were watching out for sudden mood swings after initial concerns about Accutane. But months after he began taking the drug, her grandson appeared to be nothing more than a teenager with a bright future who had even spent part of his winter school break studying for upcoming finals.

"Charles loved his mother. Charles loved me," Johnson said in a November deposition filed last month in U.S. District Court. "He was happy with either one of us. He was a remarkably resilient, cheerful, adaptable child."

Attorneys for Hoffmann-La Roche Ltd., the makers of Accutane, are asking a judge to dismiss the lawsuit before trial. No hearing date has been set and the case has been tentatively set for trial in November.

Carolyn Glynn, a spokeswoman for Hoffmann-LaRoche, declined to comment on the court filings, citing a company policy of not doing so in any legal case.

The Food and Drug Administration said it has 234 reports of suicide among Accutane users worldwide from 1982 to December 2003; that includes 179 in the United States. An estimated 13 million patients have used Accutane since its debut in 1982.

Charles Bishop began using the drug in April 2001, eight months before his suicide.

Attorneys in the civil lawsuit combed through the boy's personal effects, e-mails, junior high yearbooks and even notepad doodles looking for clues.

Julia Bishop and Johnson answered questions for more than 16 hours, the most extensive questioning of the boy's family since the tragedy. The mother and grandmother said they wanted to dispel law enforcement's characterization of Charles as a troubled loner, which for them evoked images of Dylan Klebold and Eric Harris and their 1999 massacre at Columbine High School.

The National Mental Health Association says four out of five teenagers who commit suicide show warning signs, such as a decline in school performance, writing about death or noticeable changes in eating and sleeping patterns.

But Michael Ryan, the Fort Lauderdale attorney who represents the Bishop family, said when Accutane is in the mix, there are often no warning signs.

Ryan has filed more than 30 lawsuits against the makers of Accutane on behalf of people who suffered bad side-effects, including about a half-dozen brought by families of those who committed suicide.

"Most of the suicides I have seen there have been no warning, even in retrospect," Ryan said.

The drug company's attorneys are focusing on Bishop's family history in the case.

Charles Bishop had no history of psychiatric problems and his mother testified the only psychiatric medication he'd taken was for mild attention deficit disorder when he was about 9 years old. He eventually outgrew the condition, his mother told attorneys.

But Julia Bishop and the boy's father had attempted suicide when they were teenagers. Julia Bishop had used anti-depressant medications through the years.

Dermatologist Anjali H. Singh, who treated Charles Bishop, said the family never disclosed Julia Bishop's psychological history when he prescribed Charles Bishop Accutane in April 2001 and then gradually upped his dose from 10 milligrams to 60 milligrams over the eight months.

Ryan criticized Hoffmann-LaRoche attorneys for focusing on extended family histories in such lawsuits.

"What Roche has done is put families under the microscope," he said. "They have examined families and go back generations in a way no family in America could survive."

Johnson told attorneys her daughter is haunted by questions of what could have been done differently. While by all accounts a devoted mother, Julia Bishop moved frequently hoping to find better jobs to support her son.

When asked by the drug company's attorney what they wish they might have done differently, Johnson replied, "We wished he'd never gone on Accutane."

FDA Urged To Ban Acne Med Sales Online

Mon, 02 Feb 2004 00:00:00 -0800

A doctors' group has urged the Food and Drug Administration to ban Internet sales of a popular drug to treat acne because of health dangers.

In a letter sent Monday to the FDA, the American Academy of Dermatology Association urged the agency to restrict sales of isotretinoin, commonly known as Accutane a treatment for severe cystic acne to prescriptions only. The drug is known to cause serious side effects if taken incorrectly, such as birth defects in babies born to mothers who took isotretinoin while pregnant.

The AADA said it is providing the FDA with a preliminary list of Internet sites from which isotretinoin can be purchased.

Accutane Suicide IBD Side Effects Lawyer

Mon, 02 Feb 2004 00:00:00 -0800

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Suicidal Thoughts & Behavior

Suicide Link
The Food & Drug Administration (FDA) approved Accutane in May 1982. Accutane is prescribed to combat severe acne. In 1998, the FDA advised doctors who prescribed Accutane to watch their patients for signs of depression. Afterward Hoffman-LaRoche, the maker of Accutane notified doctors that the drug "may cause depression, psychosis, and on rare occasions suicidal ideation, suicide attempts and suicide." However, the knowledge of the potential danger associated with Accutane did not become widely known until a Congressman's son committed suicide. Rep. Bart Stupak says his 17-year-old son's suicide on May 14, 2000 may be linked to the popular acne medicine. Bart Stupak Jr., known as "B.J.," shot himself in the head with his father's gun. Stupak was popular in school, a football player, and killed himself after a prom-night party. In assessing how many potential suicide cases could be linked to Accutane, Rep. Stupak stated, "We are up over 100 reports, that's just what is coming in to us, so I believe there are probably over a thousand cases," Stupak said. "The average time is 88 days from when you start taking it, and the effect is very sudden. You are doing strange things at 3 a.m. and you are dead at 7 a.m." The FDA has received reports of 66 suicides and 1,373 cases of psychiatric problems among Accutane users as of early December 2000 according to a report in USA Today. Accutane's package warning first stated potential relationship between Accutane and depression in 1986. Although French officials required that Hoff-LaRoche add the risk of suicide to the package insert of the European version of Accutane in March 1997, the FDA did not require such a change in the USA until 1999.

Birth Defects
If Accutane is taken during pregnancy or within a month of becoming pregnant, it is known to cause severe birth defects, including brain and heart defects and mental retardation. Due to the inadequacies of the SMART (System to Manage Accutane Related Teretogenicity) program initiated by Roche on April 10, 2002, and the continuation of babies born with Accutane-related birth defects, the new iPledge program began in early 2006. iPledge requires women of childbearing age to have two tests to ensure that they're not pregnant before the initial prescription, and monthly pregnancy testing before each refill. Home pregnancy tests do not suffice to fulfill this requirement. The doctor then enters the pregnancy test results into the iPledge system, and the woman is required to fill her Accutane prescription within seven days. Furthermore, women must agree to use two forms of birth control while using the drug. They also self-register on iPledge to certify that the are indeed using two forms of contraception. These programs come too late for the hundreds of children born with birth defects caused by Accutane usage.

Legal Help for Accutane Victims
If you or a loved one took Accutane and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.