Yourlawyer.com (Tamoxifen News)

Tamoxifen Label May Finally Warn About Antidepressant Risks

Tue, 02 Jun 2009 00:00:00 -0700

A study that we reported on yesterday that showed that use of some antidepressants-namely Paxil, Prozac and Zoloft-may interfere with the efficacy of tamoxifen, leading to recurrence of breast cancer, has the Food & Drug Administration (FDA) planning to warn doctors of potentially adverse interactions. According to Dow Jones News Wire, it will likely add the information on the interactions to tamoxifen's label.

Tamoxifen is used to prevent the return of estrogen-dependent breast tumors. More than 500,000 women in the U.S. are taking tamoxifen and about 30% of those women are also prescribed antidepressants to treat hot flashes, Dow Jones News Wire said.

Hot flashes are a common side effect of tamoxifen therapy. As we reported yesterday, doctors started using antidepressants for hot flashes after hormone-based treatments were linked to the development of breast cancer. However, treating tamoxifen hot flashes with antidepressants is an off-label use of such drugs.

As we reported yesterday, a study conducted by Medco Health Solutions Inc. and presented over the weekend at the American Society of Clinical Oncology's annual meeting, found breast cancer patients who took an antidepressant like Paxil, Prozac or Zoloft with tamoxifen were more than twice as likely to have their cancer return. The study, which involved 1,300 women, found that those who took such drug combos for one year had a breast cancer recurrence rate of 16% compared to a recurrence rate of 7.5% for women not taking the drugs. However, according to Dow Jones News Wire, not all antidepressants had the same impact, and the study showed women on drugs like Celexa, Lexapro and Luvox didn't have a statistically higher rate of cancer recurrence.

According to a report on Bloomberg.com, tamoxifen works by combining with the CYP2D6 enzyme, which is produced by the liver. This produces endoxifen, a substance known to fight tumors. But some antidepressants, including Paxil, Prozac and Zoloft, block the CYP2D6 to varying degrees, which likely impacts the efficacy of tamoxifen.

Prior to the Medco study, lab studies had shown that some antidepressants could impact tamoxifen. As we reported yesterday, the FDA had already taken a look at interactions between tamoxifen and antidepressants. According to Bloomberg.com, the 2006 review concluded that data on the effect should be added to tamoxifen labeling; however, to date, there is no such statement on this risk on the medication’s label.

According to Dow Jones News Wire, Larry Lesko, director of the FDA's Office of Clinical Pharmacology, said now that the FDA has evidence about clinical outcomes as a result of the drug interaction, it will likely add that information to tamoxifen's label.

Tamoxifen Increases Tumor Growth in Some Breast Cancer Patients

Thu, 04 Dec 2008 00:00:00 -0800

Tamoxifen, a drug routinely given to breast cancer patients, could actually increase tumor growth in certain patients, a new study has found. The authors of the study, which was published in the journal Breast Cancer Research, said their work could eventually lead to tests that could screen out patients who might be endangered by taking tamoxifen.

According to the National Cancer Institute website, Tamoxifen has been used for more than 30 years to treat breast cancer in women and men. Tamoxifen interferes with the activity of estrogen, a female hormone. Estrogen can promote the development of cancer in the breast. Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) for the prevention of breast cancer and for the treatment of breast cancer, as well as other types of cancer.

According to Reuters.com, tamoxifen is given to most patients for five years after they are diagnosed with breast cancer to prevent the disease from returning. However, some develop resistance, which means their tumor is more likely to recur. Last month, a British team identified a called Pax2 which contributed to the development of such resistance, Reuters said.

According to this latest tamoxifen study, use of drugs like tamoxifen in patients with low levels of another protein - E-cadherin - may promote more harmful cancer cell behavior. The E-cadherin protein makes cells stick together. In their experiments, researchers from Cardiff University found that when the protein was at reduced levels, tamoxifen caused cancer cells to move around much more aggressively. This activity can lead to tumor growth, they said.

The researchers said that the next stage of their work would be to determine an actual level of the protein that would cause tamoxifen to fail. Further research could lead to the development of screening tests to identify breast cancer patients who should be given alternatives to drugs like tamoxifen.

HRT Use Increases GERD

Wed, 10 Sep 2008 00:00:00 -0700

Women taking hormones to relieve menopause symptoms and women taking SERMs—selective estrogen receptor modulators—to treat breast cancer and osteoporosis, have a higher risk of developing symptoms of gastroesophageal reflux disease (GERD), according to a study in the current issue of Archives of Internal Medicine.

SERMs, such as tamoxifen, are popular in the treatment of breast cancer, while raloxifene is prescribed for the prevention and treatment of postmenopausal osteoporosis. In the women studied, about two-thirds experienced GERD during the course of one year; 20 to 30 percent experienced GERD problems at least weekly, some more frequently. "For a long time, people have thought that female hormones are in some way associated with heartburn," said study author Dr. Brian Jacobson, an assistant professor of medicine at Boston University School of Medicine. "Women who are pregnant, even in the first trimester before a great big belly pushes on the stomach, already experience heartburn." Women on oral contraceptives also sometimes experience a relaxation of the lower esophageal sphincter, which allows stomach acids to rise up into the esophagus.

Up until now, no one has studied if exogenous hormones—hormones introduced externally—have an effect on GERD, although some studies have indicated that postmenopausal hormones might increase GERD symptoms in women who are overweight or obese. In this study, information on 51,637 postmenopausal women enrolled in the Nurses' Health Study were reviewed. Women provided information on postmenopausal hormone use and GERD symptoms. The review was conducted every two years from 1976 through 2002. Women taking hormones experienced a 46 percent greater risk of having GERD symptoms as compared with women who never used postmenopausal hormones. Women actively taking estrogen had a 66 percent raised risk; those using combined estrogen and progesterone had a 41 percent increased risk. The study also found that the chances of developing GERD symptoms increased with higher hormone doses and longer duration of use. Active SERM users experienced a 39 percent increased risk, while women taking over-the-counter preparations saw an increased risk of 37 percent.

"This is important for a couple of reasons, one just for proof of principle in terms of the mechanisms and pathophysiology," Jacobson said. "We had always suspected [exogenous hormones] might do it. Now, we have more evidence that hormones do somehow cause people to get more heartburn. Although biological mechanisms remain unclear, researchers believe hormones may lower pressure in the esophageal sphincter. Because of other risks—heart attack and breast cancer—most experts recommend women limit their postmenopausal hormone use. Jacobson said that if a woman does take hormones and experiences heartburn, she might consider an alternative for her menopausal symptoms. A woman [taking hormones who develops GERD] may need additional medication or she may make the decision with her doctor that it's not worth it to continue hormones," said Dr. Jennifer Wu, an obstetrician/gynecologist with Lenox Hill Hospital in New York City. "GERD is something we will have to keep an eye on when putting patients on hormones. It's not an obvious symptom to patients … so we may need to inform patients ahead of time."

Panel suggests adding drug label warning

Wed, 18 Oct 2006 00:00:00 -0700

Post-menopausal women who take tamoxifen to treat breast cancer face a greater risk of recurrence if they have a specific genetic variation, federal health advisers said Wednesday in recommending that a warning be added to the drug's label.

Recent studies have found tamoxifen does not work as well in women with breast cancer who carry a variant of a gene called CYP2D6. An estimated 7 percent to 10 percent of women with breast cancer may have that special form of the gene, which affects how their bodies process the drug.

A panel of Food and Drug Administration advisers recommended the agency change tamoxifen's label to warn post-menopausal women of that potential risk.

"The bottom line is, the consensus was that the information is important enough to be included in the label," said FDA pharmacology chief Dr. Lawrence Lesko.

However, the clinical pharmacology panel left it to the FDA to decide whether the drug's label should recommend genetic testing of post-menopausal breast cancer patients before they are prescribed tamoxifen. Still, the FDA will consider adding such language perhaps in the form of a suggestion to the label, Lesko said.

The FDA first approved tamoxifen in 1977. It is made in generic form by multiple drug companies.

The drug is now use to both treat breast cancer and to prevent the disease in women who may be predisposed to it. The drug blocks estrogen, a hormone that stimulates the growth of most tumors after menopause.

Lesko said the label changes could take six months to put in place. Since 2003, the FDA has taken three other drugs before the panel to discuss adding genetic-specific information to their labels. They include the blood-thinner warfarin; updates to its label are forthcoming, Lesko said.

The FDA isn't required to follow the advice of its outside panels, but usually does.

Panel tells FDA Tamoxifen label should add recurrence risk

Wed, 18 Oct 2006 00:00:00 -0700

A panel of experts told the Food and Drug Administration Wednesday that the label of cancer drug Tamoxifen should be changed to include evidence that certain women with estrogen-related breast cancer may be at higher risk for recurrence of the disease.

Tamoxifen is designed to block estrogen in women with the most common type of breast cancer. By blocking estrogen, the drug controls tumor growth. The drug, usually taken for five years, is used as additional therapy following primary treatment for breast cancer. It is also used for the reduction in breast cancer incidence in high-risk women.

Studies, however, have suggested that the drug isn't as effective in patients who have poor activity of an enzyme called CYP2D6. That enzyme is responsible for metabolizing tamoxifen into endoxifen, which suppresses estrogen-dependent cell proliferation.

In general, some women are CYP2D6-poor metabolizers because of genetic predisposition.

The advisory panel was first asked whether the tamoxifen label should include information about increased risk for breast cancer recurrence in CYP2D6-poor metabolizers. They were then asked whether there is sufficient scientific and clinical evidence to support revisions of the tamoxifen label recommending that women be tested for the enzyme capabilities before being prescribed the drug.

While many of the panel members said more trials should be conducted on the issue, they overall agreed that the label should be modified.

"The risk signal needs to be indicated very clearly to patients," said panel member Howard McLeod, a director at University of North Carolina's Institute for Pharmacogenomics & Individualized Therapy. "Patients may choose to continue with tamoxifen for other reasons, but at least they need to be informed of the risk that is present."

On the testing recommendation, McLeod said "I believe this information should suggest testing, but not require testing. The data is not there to make it malpractice not to test, but the data is there to suggest that it should be taken into strong consideration."

McLeod said the testing would cost as much or even less than other testing breast cancer patients undertake. "It is a very little added expense, and yet it can help making a more objective decision on the therapy."

The panel's decision isn't official and doesn't indicate the FDA will seek a change on the drug's label.

The agency first approved tamoxifen under the brand name Nolvadex in 1977 by then-manufacturer Zeneca Pharmaceuticals, which later merged with Astra to form U.K.-based AstraZeneca PLC (AZN).

Since then, other companies, including a unit of Barr Laboratories Inc. (BRL) and Teva Pharmaceutical Industries Ltd. (TEVA), have been allowed to sell tamoxifen as a generic drug. AstraZeneca stopped selling the drug in June because of declining sales.

Matthew Goetz, assistant professor of oncology at Mayo Clinic College of Medicine, said it is important to discuss the efficacy of tamoxifen in women who have poor enzyme activity because there are now other treatments available that could be more effective for those patients.

"Tamoxifen is not the only kid on the block anymore," he said in a presentation.

According to Goetz, while pre-menopausal women who have estrogen-positive breast cancer still have Tamoxifen as their only treatment option, post-menopausal women can also take newer drugs known as aromatase inhibitors.

Last year, the FDA approved the drugs, which include AstraZeneca's Arimidex, Novartis AG's (NVS) Femara and Pfizer Inc.'s (PFE) Aromasin, to treat post-menopausal women with early-stage breast cancer. The drugs were originally approved to treat more advanced cases of breast cancer and in some cases to use after women had been on tamoxifen for five years.

Breast-Cancer Drug Tamoxifen Appears to Boost Risk of Stroke

Mon, 11 Oct 2004 00:00:00 -0700

The breast cancer drug tamoxifen appears to increase a woman's risk of having a stroke, although the overall risk is small, according to a systematic review of nearly 25 years worth of clinical trials of the drug.

Doctors say the finding should not stop breast cancer patients from taking tamoxifen. But it could be a factor for women who are considering the drug to prevent the disease, especially those who are at high risk for stroke.

For years, doctors have known that tamoxifen increases the risk of venous thromboembolism, a type of blood clot that often forms in the legs and can migrate to the lungs and other parts of the body.

Whether tamoxifen increases the risk of a stroke has been unclear; a couple of studies have found a reduced risk and several found an increased risk.

To determine the stroke risk posed by tamoxifen, Duke University researchers pooled findings from nine clinical trials involving about 40,000 breast cancer patients.

Over a five-year period, women taking tamoxifen had a 29 percent greater risk of having any type of stroke and an 82 percent greater chance of ischemic stroke, compared with women who received placebos or some other drug.

The ischemic stroke risk was small, 0.71 percent for tamoxifen users, compared with 0.39 percent for women who did not get the drug. Ischemic stroke, the most common type, is caused when a blood vessel in the brain is blocked.

That translates to seven women out of 1,000 having a stroke while on tamoxifen over five years, said lead author Cheryl Bushnell, a neurologist at Duke University Medical Center.

She said the risk of stroke with tamoxifen was lower than with the recently recalled arthritis drug Vioxx, which had a risk of 75 heart attacks or strokes per 1,000 after five years. Tamoxifen also has been associated with a slightly increased risk of endometrial cancer.

"My goal is to increase awareness of women and their physicians of the possibility of stroke risk with tamoxifen," Bushnell said. "Many oncologists already screen their patients for stroke risk factors prior to starting tamoxifen and this study reinforces that practice."

Tamoxifen also has beneficial side effects, including improving bone density, said Yee Chung Cheng, an oncologist at the Medical College of Wisconsin who practices at the VA Hospital and Froedtert Memorial Lutheran Hospital.

While an 82 percent increase risk of stroke seems large, the overall stroke risk remains small, he said.

"We've been using tamoxifen for many, many years," Cheng said.

And for those women who are at higher risk for stroke, there are other breast cancer drugs they can take instead of tamoxifen, he said.

Mark Alberts, a professor of neurology and director of the stroke program at Northwestern University Feinberg School of Medicine, said the new study did a good job of pulling together all the earlier research on tamoxifen and stroke risk.

"It broadens our understanding of risk factors for stroke," Alberts said.

Exactly how tamoxifen increases stroke risk is not certain. It is known that cancer patients, in general, are at higher risk for blood coagulation problems. And earlier research showed tamoxifen increases the risk of venous thromboembolism.

Part of the high stroke risk might be due to those clots traveling to the brain, doctors said.

"We have to discuss this with patients so they have their eyes open," said Douglas Dulli, a professor of neurology and public health medicine at the University of Wisconsin-Madison.

Women who might consider taking tamoxifen to prevent breast cancer, especially if they are at increased risk of having a stroke, should discuss it with a doctor, he said.

Tamoxifen Stroke Blood Clot Cancer Side Effects Lawyer

Mon, 11 Oct 2004 00:00:00 -0700

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Post-menopausal women who are prescribed Tamoxifen to comabt breast cancer face a greater risk of recurrence if they have a specific genetic variation federal health advisers warned on October 18, 2006. A panel of FDA advisers strongly suggested the agency change Tamoxifen's label to warn post-menopausal women of the newest potential risk. New studies discovered that Tamoxifen does not work as well in women with breast cancer who carry a variant of a gene called CYP2D6. Approximately 7% to 10% of women with breast cancer may have this particular form of the gene, which affects how their bodies process the drug.

"The bottom line is, the consensus was that the information is important enough to be included in the label," said FDA pharmacology chief Dr. Lawrence Lesko. On the other hand, the clinical pharmacology panel left it to the FDA to decide whether the drug's label should recommend genetic testing of post-menopausal breast cancer patients before they are prescribed Tamoxifen. Still, the FDA will consider adding such language perhaps in the form of a suggestion to the label, Lesko said. Lesko said the label changes could take six months to put in place. Since 2003, the FDA has taken three other drugs before the panel to discuss adding genetic-specific information to their labels. They include the blood-thinner warfarin; updates to its label are forthcoming, Lesko said.

Tamoxifen (Generic: Nolvadex) is a commonly prescribed drug to treat breast cancer increases the chances of stroke, new research shows. Tamoxifen has been linked to cause the following side effects: pulmonary embolism (blood clots in the lung) and cancer of the uterus (womb). Tamoxifen has been prescribed to more than half of all patients suffering from breast cancer, can in some cases actually fuel tumor growth and enhance the probability of a relapse, Swedish researchers recently stated. Since the 1970s Tamoxifen has been widely prescribed to combat breast cancer since it has shown to counteract the cancer-promoting effects of estrogen in the breast by binding itself to the estrogen receptor in the cancerous cell, thus impeding tumor progression.

Based upon new research carried out at the Malmo University Hospital, UMAS, in southern Sweden, Tamoxifen can have the opposite effect on certain types of tumors. "The results show that Tamoxifen is a very resourceful treatment for most patients. But for approximately 15% of tumors that contain many copies of the cell-splitting gene cyclin D1 tamoxifen however appears to have the opposite effect," researcher Karin Jirstroem said in a statement.

The study conducted by Jirstroem and her colleagues was based on assessments of patients from southern Sweden who had been treated with the drug. It was recently published in the US medical journal Cancer Researcher.

After analyzing nine prior studies the researchers find that Tamoxifen use was associated with an 82% increase in ischemic [clot-related] stroke risk and a 29% increase in the risk for all strokes. The study is published in the October issue of the journal Neurology. The increase in risk translated into seven additional strokes among 1,000 patients taking the drug for five years, according to study co-author Cheryl D. Bushnell, MD.

Millions of women have taken Tamoxifen during the last 30 years, but the risks and benefits of the drug have long been debated. Since the drug can act like an estrogen in certain tissue, it can increase the risk of blood clots and endometrial cancer. It has been unclear whether Tamoxifen use increases a woman's stroke risk. A recently published review of studies showed almost a 50% increase in the risk of all types of stroke, but Bushnell and colleague Larry Goldstein, MD, of Duke University Medical Center guessed the risk of blood clot-related strokes might be higher.

If you or a loved one took Tamoxifen and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.