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Drug-Induced Diseases All too Often, the Cure is Becoming Worse than the IllnessSep 1, 2007
The abundance of prescription drugs and Over the Counter (OTC) medications now flooding the market has produced a rapidly expanding number of unintended (but nonetheless foreseeable) problems with respect to adverse drug reactions.
Some of the reasons for the significant increase in drug-induced diseases are: (1) hasty “fast track” FDA approvals of many prescription drugs without adequate long-term clinical testing; (2) improper use of OTC medications brought about by dosing errors, misuse, or failure to take potential interactions with prescription drugs into consideration; (3) failure to associate the reaction or disease with a particular drug or combination of drugs; and (4) simple probability – a greater number of more powerful drugs.
Currently, there are over 9.6 million adverse drug reactions each year in older Americans alone. As one study found, however, 37% of the adverse reactions suffered by the elderly were not reported to a doctor. One possible reason for this is elderly patients are less likely to associate a reaction to a particular drug (or combination of drugs) they are taking. In addition, a majority of doctors surveyed admitted they did not explain potential adverse reactions to their patients.
The consumer watchdog group Public Citizen (as part of its publication, Worst Pills Best Pills), analyzed a number of reliable studies (mainly in the U.S.) and made the following estimates:
- Each year there are approximately 28,000 cases of life-threatening heart toxicity, in hospitals alone, from adverse reactions to digoxin (DIGITEK, LANOXICAPS, and LANOXIN), which, in older adults, is the most commonly used form of digitalis (used to regulate the speed and strength of heart beats).
- Each year, some 41,000 older adults are hospitalized — and, of that number, about 3,300 die from ulcers caused by NSAIDs (nonsteroidal anti-inflammatory drugs, usually prescribed for arthritis). Thousands of younger adults are also hospitalized.
- At least 16,000 injuries from auto crashes each year involving older drivers are attributable to the use of psychoactive (affecting the mind and behavior) drugs – in particular benzodiazepines and tricyclic antidepressants.
- About 32,000 older adults suffer from hip fractures each year that are attributable to drug-induced falls. These injuries lead to over 1,500 deaths. “In one study, the main categories of drugs responsible for the falls leading to hip fractures were sleeping pills and minor tranquilizers (30 percent), antipsychotic drugs (52 percent), and antidepressants (17 percent). All of these categories of drugs are often prescribed unnecessarily, especially in older adults.”
- Approximately 163,000 older Americans suffer from serious mental impairment (memory loss, dementia) either caused or worsened by drugs. In a study in the state of Washington, in 46 percent of the patients with drug-induced mental impairment, the problem was caused by minor tranquilizers or sleeping pills; in 14 percent, by high blood pressure drugs; and in 11 percent, by antipsychotic drugs.
- Some two million older Americans are addicted or at risk of addiction to minor tranquilizers or sleeping pills as a result of using them on a daily basis for at least a year. (There is no reliable evidence that these tranquilizers are effective for more than four months, and the sleeping pills for more than 30 days.)
- “Drug-induced tardive dyskinesia has developed in 73,000 older adults; this condition is the most serious and common adverse reaction to antipsychotic drugs, and it is often irreversible.” Tardive dyskinesia is characterized by involuntary movements of the face, arms and legs. Since some 80% of older patients receiving antipsychotic drugs do not have conditions such as schizophrenia that justify the use of such powerful drugs, many of these patients suffer unnecessary serious side effects.
- “Drug-induced parkinsonism has developed in 61,000 older adults also due to the use of antipsychotic drugs such as haloperidol (HALDOL), chlorpromazine (THORAZINE), trifluoperazine (STELAZINE), fluphenazine (PROLIXIN), and thioridazine (MELLARIL). (Other parkinsonism-inducing drugs include: metoclpramide (REGLAN), prochlorperazine (COMPAZINE), and promethazine (PHENERGAN), prescribed for gastrointestinal problems. The problem is two-fold. Doctors fail to suspect that the condition is caused by one of the drugs mentioned above and, as a result, they often add a second drug to treat the disease that has actually been caused by the first drug.
As stated in Worst Pill Best Pills: “A serious problem exists because both doctors and patients do not realize that practically any symptom in older adults and in many younger adults can be caused or worsened by drugs. Some doctors and patients assume that what are actually adverse drug reactions are simply signs of aging. As a result, many serious adverse reactions are entirely overlooked or not recognized until they have caused significant harm.”
SOME INDIVIDUAL CASE STUDIES INVOLVING DRUG-INDUCED DISEASES
Worst Pills Best Pills was able to acquire information concerning specific cases of drug-induced disease. For purposes of confidentiality, the publication did not use the last names of the individuals involved.
Woman homebound due to misprescribed heart drug: “54-year old woman named Liz was prescribed the heart drug amiodarone (CORDARONE) to treat a common heart condition. She was not told that the drug was not approved by the Food and Drug Administration (FDA) for her condition. The pharmacy leaflet mentioned nausea and dizziness as side effects, but not lung toxicity. She is now dependent on an oxygen tank to breathe and does not have the strength to leave her house.”
Man develops parkinsonism from antipsychotics prescribed for irritable bowel syndrome: “Larry was an otherwise healthy 58-year-old man with diarrhea believed to be due to ‘irritable bowel syndrome.’ He was given trifluoperazine (STELAZINE), a powerful antipsychotic, to ‘calm down’ his intestinal tract. STELAZINE is not even approved for treating such medical problems. Six months after starting STELAZINE, Larry developed severe parkinsonism, a neurological condition characterized by tremors, limited movements, rigidity and postural instability. To correct this, Larry was started on L-dopa (also known as levodopa), a drug to treat Parkinson’s disease. Presumably, the doctor did not realize the parkinsonism was drug-induced, and the STELAZINE was continued. For seven years, Larry took both drugs until finally seeing a Parkinson’s specialist. The specialist recognized the real cause of his problem, stopped the STELAZINE, and slowly withdrew the L-dopa over a six-month period. Larry’s severe, disabling parkinsonism cleared completely.”
“The same Parkinson’s specialist who ‘cured’ Larry of his drug-induced parkinsonism saw, in just three years, 38 other patients with drug-induced parkinsonism and 28 with drug-induced tardive dyskinesia, a syndrome of involuntary movements.”
“None of these patients were psychotic, the one condition for which antipsychotic medications are approved. Rather, the most common reasons for using the parkinsonism-inducing drugs were chronic anxiety and gastrointestinal complaints. The most frequent culprit (in 19 of these 39 patients) was REGLAN, usually prescribed for heartburn or for nausea and vomiting. Doctors often prescribe REGLAN before trying other more conservative and safer methods. Other drugs that brought on parkinsonism included prochlorperazine (COMPAZINE), haloperidol (HALDOL) and chlorpromazine (THORAZINE).”
Confusion and hallucinations caused by ulcer drugs: “Leticia wrote to Public Citizen about her 80-year-old father, saying that she had to repeatedly ask his doctor about the possible role of her dad’s ulcer drugs in causing confusion and hallucinations before the doctor listened. Her father had tried three different drugs – cimetidine (TAGAMET), ranitidine (ZANTAC) and famotidine (PEPCID) – for his ulcers, and each had caused these side effects. When the doctor finally switched Leticia’s father to an antacid – aluminum hydroxide and magnesium hydroxide (MAALOX) – his mind completely cleared and he was his old self, no longer confused or hallucinating.”
Woman develops reversible mental impairment from tranquilizer: “The first time 79-year-old Sally saw her physician son-in-law after several months, he noted that she had suffered severe impairment of her otherwise sharp mind. She was acting confused and, for the first time in her life, was unable to balance her checkbook. When he questioned her, she was able to remember that her problem had started around the time she was put on the tranquilizer lorazepam (ATIVAN). After this link was discovered, the drug was slowly discontinued and the mental impairment disappeared.”
Man has auto accident after one dose of tranquilizer: “Ben, a 64-year-old, was scheduled to have a biopsy done at a local hospital one morning. The doctor gave him a free sample of a tranquilizer, alprazolam (XANAX), to take an hour or so before the procedure so that he would be relaxed for the biopsy. Ben was not told that he should not use the drug if he was going to drive. While driving to the hospital for the biopsy, he blacked out. The car went over a fence and sustained $6,000 worth of damage, but fortunately Ben was unhurt.”
Dangerously slow heart rate with propranolol use in the elderly: “Shara, a 60-year-old assistant at a senior citizens’ center, was started on propranolol (INDERAL, INDERAL LA) to treat her high blood pressure. Unfortunately, her doctor did not realize that the dose of this sometimes useful drug must be reduced in older adults, and the dose she was prescribed was too high for her. Two days after she started taking the drug, she began feeling very weak. The side effect was so bad that by the third day on the drug, she went to a hospital emergency room, where her pulse rate was found to be 36 beats per minute. This dangerously low rate fully explained her weakness. The drug was stopped, and Shara’s heart rate returned to normal. Later a low dose of a different drug was prescribed and produced no side effects.”
Child dies from drug prescribed for attention deficit hyperactivity disorder: “Jamal, a bright 7-year-old boy, was prescribed an antidepressant, imipramine (TOFRANIL), to treat attention deficit hyperactivity disorder. His parents were not provided with complete, accurate information about the drug. As a result, they were unaware that the drug can cause life-threatening heartbeat irregularities (called arrhythmias), that the dose prescribed to Jamal was too high and that the tremor and convulsions that Jamal began to have were actually side effects from the TOFRANIL. Treatment with the drug was continued, and one day, while at school, he collapsed and died of an arrhythmia. If his parents had been adequately warned about this drug, Jamal might still be alive today.”
Poor prescribing is often the cause of symptoms
As pointed out in Worst Pills Best Pills: The World Health Organization (“WHO”), in discussing the problem of side effects in the elderly, has stated some principles applicable to people of all ages:
“Quite often, the history and clinical examination of patients with side effects reveal that no valid indication [purpose] for the offending drug has been present ... Adverse reactions can to a large extent be avoided in the elderly by choosing safe and effective drugs and applying sound therapeutic principles in prescribing, such as starting with a small dose, observing the patient frequently, and avoiding excessive polypharmacy [the use of multiple drugs at the same time].”
In short, it is frequently the case that patients who suffer adverse drug reactions are victims of drugs that they should not have been taking that way in the first place.
In 1992, a study published in Medical Care analyzed prescriptions given to people being discharged from a particular community hospital. The study focused on patients who were prescribed three or more drugs to treat chronic illnesses. The study reached some rather unsettling conclusions with respect to the doctors’ prescribing practices and as evidence of the potential damage that these prescribing practices can do to older adults.
Of the 236 people intensively studied:
- 81% had one or more prescribing problems with the prescriptions they were given, including inappropriate drugs, doses or schedule;
- 60% had been given one or more prescriptions for a drug that was an inappropriate choice of therapy because it was either “less than optimal medication given the patient’s diagnosis” or there was no established indication for it;
- 50% were given either too high or too low a dose of the drug;
- 44% were given a combination of drugs that can result in harmful drug interactions;
- 20% were given drugs that unnecessarily duplicated the therapeutic effect of another drug they were taking.
Complete lists of the most common drug-induced side effects along with the drugs that can cause them are available free of charge on www.WorstPills.org . Below are some of the symptoms that are also frequently caused by drugs. They are the kinds of problems that you or many doctors might instead first attribute simply to “growing old” or “getting nervous.” CLICK HERE To see the complete list.
“Although some of these adverse effects occur most commonly in older adults, all of them have also been documented in younger people, although sometimes not as often.”
To be sure, OTC medications can also produce serious drug-induced diseases when taken improperly or for extended periods of time. For example, Acetaminophen causes many problems as it is available in a variety of different strengths. It is also found in many combination medications, both prescription and OTC. Prescription labels of combination products with acetaminophen can be potentially confusing for the patient. For example, hydrocodone 10/650 has 650 mg of acetaminophen, but many patients are not sure what that means.
Acetaminophen can be toxic, even though it can be purchased over-the-counter, and acetaminophen-induced liver toxicity accounts for more than 40% of all cases of acute liver failure in the United States.
Recent TV advertisements for Tylenol advise viewers that the makers of the drug would rather you not take it than take more than the recommended dose.
For the past two years, there has also been an ever-increasing awareness of the potentially fatal effect over-the-counter (OTC) cold remedies designed for “children” have when given to infants.
Initially, in November 2005, findings were released by the Montgomery, Ohio, Coroner’s Office after an investigation unearthed a rash of infant deaths linked to improper medicating with cold remedies that were intended for older children. This prompted health officials in other states as well as at the Centers for Disease Control (CDC) and the Food and Drug Administration (FDA) to start their own inquiries into the apparent harmful and often deadly confusion between “pediatric” and “infant” dosages for OTC cold medications.
At the time, the Coroner’s Office said that they encountered 10 deaths over an 8-month period in infants less than 12 months old with toxicology findings that included a variety of drugs commonly found in OTC cold medications.
The drugs detected were ephedrine, pseudoephedrine, dextromethorphan, diphenhydramine, chlorpheniramine, brompheniramine, ethanol, carbinoxamine, levorphanol, acetaminophen, and the anti-emetic metoclopramide.
Toxicology findings were confirmed in 2 different matrices in 9 of the 10 cases and by 2 different analytical methods. The majority of these deaths were either toxicity from the OTC cold medications directly or as a contributory factor in the cause of death.
The toxicologists involved in the investigation said that these specific cases demonstrated that the administration of some OTC cold medications is not safe and can result in fatal levels of toxicity in infants who have been exposed to contraindicated doses of such drugs or their active ingredients.
Since 2005, there have been two other major occurrences of infant deaths linked to improper dosages of over-the-counter medications, causing physicians and medical professionals to advise patients to seek medical advice from a professional even in regards to OTC medications when it comes to infants and children. When mistakes can be fatal, parents and caregivers can never be too cautious and sometimes interpreting labels can be more difficult than it seems.
On February 26, 2006 the Chicago Tribune ran a story regarding the deaths of two Kane County infants within a 24-hour period and attributed these deaths to accidental overdoses of prescription cold medicines.
The coroner for Kane County requested that the FDA join the investigation because there appears to be a “trend” developing in the form of a dramatic increase in the number of “troubling” deaths in which accidental overdosing may have been involved.
An FDA spokesperson acknowledged that it was aware of the cases and that the agency was actively participating in the investigation.
Although the Illinois deaths are troubling in and of themselves, recent reports from around the U.S. indicate that accidental overdosing of infants is a serious and growing problem. Moreover, the problem is not limited to prescription drugs, as life-threatening overdoses of OTC medications also appear to be on the rise.
The Chicago Tribune article noted a similar situation to the Ohio deaths in at least one of the deaths in Kane County where “the prescribed dosage of medicine was 0.2 milligrams, he said, but the dropper that was used, which measures 1 milligram when full, could lead a confused caregiver to deliver 2 droppers-full of medicine instead of just two-tenths of one dropper.”
Researchers in Atlanta found that prescription and over-the-counter cough and cold remedies were responsible for the deaths of three infants.
The autopsies of two boys and one girl, between the ages of one to six months, revealed that all three children had high levels of the nasal decongestant pseudoephedrine in their blood.
According to the investigators, the cough suppressant dextromethorphan and Tylenol (acetaminophen), were noticeably present in the blood of two of the infants. In addition, the blood levels of pseudoephedrine found in the children were nine to 14 times higher than the recommended doses of the decongestant for children who are ages two to 12 years.
"Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children ages younger than 2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting a health-care provider and should follow the provider's instructions precisely," the investigators wrote.
They went on to say that clinicians should also be careful when administering or prescribing cough and cold medications and fever reducers to children under the age of 2. Most children’s medications are not intended for children under the age of 2 and even giving small dosages can cause harmful effects.
Clinicians should also always ask caregivers if they are using or plan to use OTC medications before prescribing any other drugs to treat infant illnesses to make sure that there are no fatal combinations or possibilities for overdose.
Sadly, all three infants had ingested cough-and-cold remedies containing pseudoephedrine, and one had even been given both a prescription preparation and OTC medication containing the vasoconstricting decongestant.
Two of the children had also been given prescriptions containing the antihistamine carbinoxamine. Carbinoxamine was banned by the FDA following the reports of these infant deaths, citing that it contained medications that they had never approved. Since those deaths occurred, the FDA banned the manufacture of carbinoxamine-containing medications that the agency had not specifically approved.
Although the occurrence of adverse events associated with the use of cough and cold remedies in children is low, the fact that these reports continue to surface serves to remind us that these drugs are not now, nor have they ever been, completely safe for use in infants.
The correct and safe dosages for prescription and over-the-counter (OTC) drugs are almost always dictated to a large extent by the weight and age of the patient.
Infants, children, adolescents, adults, and the elderly are differentiated between when it comes to how much of a drug can be tolerated at any given time as well as if taking a particular drug is even proper in the first place.
Dosage variations or restrictions based on age and/or weight differentials are commonly included in “dosing charts” on a drug’s package or information label. Pharmacists also provide computer printouts of this data when necessary.
While healthcare professionals always have access to this information and are expected to adhere to it when prescribing a medication or suggesting an OTC remedy, the same cannot be said of consumers, however.
All to often, patients “share” prescription medication with friends or relatives believing that it is safe as long as the other person has (what appears to be) the same medical problem. Thus, it is not uncommon for some very powerful (and dangerous) prescription medication to find its way to people who should not be taking it at all or who need a completely different dosage (or drug) because of their age or weight.
The problem with OTC medications is even more serious since there is usually no medical professional involved in the decision as to which product is taken and how much of it is used. Dosing charts are often ignored, thrown away, or misunderstood. There may even be problems with the clarity of the instructions or the accuracy of measuring devices included with the product. This problem is only getting worse as more and more prescription drugs are being approved in OTC varieties or dosages.
In August of 2005, for example, the FDA announced that Perrigo Co., was voluntarily recalling all lots of four types of its concentrated infants’ liquid pain, cough, and cold drops that come packaged with syringes that could cause the youngest infants to receive overdoses of the various active ingredients including acetaminophen.
The oral syringes which Perrigo distributed with these over-the-counter liquid medications were not marked to measure doses of less than 1.6 milliliter which may be prescribed for children younger than 2 and less than 24 pounds. Ingesting too much acetaminophen, a pain-relieving ingredient, may cause liver damage. Previously, the medications had been distributed with droppers that had different markings. The new markings "caused some confusion among consumers and health-care professionals and may lead to improper dosing," the FDA said.
Taking a few extra OTC painkillers to get relief, multiplying or dividing recommended dosages depending on a child’s weight, or ignoring warnings concerning dangerous interactions can, it seems, be deadly.
Each year, OTC drug overdoses and interactions send thousands of people to hospital emergency rooms and kill scores of others. When a parent or caregiver decides, without any medical advice, that half a dropper of a children’s cold remedy is perfectly fine for a 18-pound, 10-month-old infant simply because the recommended dose for a much heavier 2-year-old child is one full dropper, the stage is set for a potentially deadly overdose. An infant’s developing bodily systems are often far too immature (or even undeveloped) to expose to toxic medications without specific medical advice and supervision.
On September 28 of this year, the New York Times carried the following article by Gardiner Harris, entitled “Ban Sought on Cold Medicine for Very Young.”
The following excerpts from that article are relevant to the problems discussed above.
“Safety experts for the Food and Drug Administration urged the agency on Friday to consider an outright ban on over-the-counter, multisymptom cough and cold medicines for children under 6.
The recommendation, in a 356-page safety review, is the strongest signal yet that the agency may take strong action against the roughly 800 popular medicines marketed in the United States under names like Toddler’s Dimetapp, Triaminic Infant and Little Colds.
The next step in the process is a meeting of outside experts on Oct. 18 and 19 to examine the medicines’ safety and offer recommendations to the agency.
In the new safety review, the agency’s experts suggested that all ‘infant’ cough and cold formulations be removed from the market, and that the droppers, cups and syringes included with products for children be standardized to reduce the risks of confusion and overdose.
The reviewers wrote that there is little evidence that these medicines are effective in young children, and there are increasing fears that they may be dangerous. From 1969 to 2006, at least 54 children died after taking decongestants, and 69 died after taking antihistamines, the report said. And it added that since adverse drug reactions are reported voluntarily and fitfully, the numbers were likely to significantly understate the medicines’ true toll.
The Consumer Healthcare Products Association, an industry trade group that has consistently defended the safety of pediatric cough and cold medicines, recommended in its own 156-page safety review, also released on Friday, that the F.D.A. consider mandatory warning labels saying that they should not be used in children younger than 2. Many cough and cold medicines now advise parents to “consult a physician” before use in such children.
The proposed warnings ‘are recommendations that we have brought forth, and we look forward to having a thorough discussion with the F.D.A.’, said Virginia Cox, a spokeswoman for the trade group.
Despite the industry’s recommendation, many companies — including such giants as Johnson & Johnson — continue to sell cough and cold medicines with “infant” in their titles and pictures of babies on their labels.
Mark Boston, a spokesman for a Johnson & Johnson subsidiary that sells pediatric cough and cold medicines, said the company ‘supports the materials’ that the trade association submitted to the F.D.A., but declined to say why the company continues to sell such products as Concentrated Tylenol Infants’ Drops Plus Cold.
Dr. Joshua Sharfstein, Baltimore’s commissioner of health and an author of a petition that led the F.D.A. to conduct its current review, cheered its new report, saying it raised serious questions about why anyone would give cough and cold medicines to young children.
‘These products are used by hundreds of thousands of kids every year, but no one can say that they’re safe or effective’” he said.
The petition followed a study by the Centers for Disease Control and Prevention that found that more than 1,500 children under the age of 2 had suffered serious health problems between 2004 and 2005 after being treated with common cough and cold medicines.
Current figures on the medicines’ sales and use are not available, but in 1994 researchers reported in The Journal of the American Medical Association that more than a third of all 3-year-olds in the United States were given over-the-counter cough and cold preparations in one 30-day span.
The petition noted that in 1990, Americans spent nearly $2 billion on these medications, and it said that in a typical drugstore, more than 30 separate cough and cold preparations are marketed to parents for use in children.
Also on Friday, the F.D.A. warned the makers of nearly 200 unapproved prescription medicines containing the pain-and-cough-relief drug hydrocodone that by Oct. 31 they must stop making these products for children under 6.
Makers of all other unapproved hydrocodone products have until Dec. 31 to stop making them.
Hydrocodone is a narcotic that is widely used to treat pain and suppress cough. There are seven F.D.A.-approved prescription cough products containing hydrocodone, and doctors can continue to write prescriptions for those.
The agency’s safety review and its decision to ban unapproved hydrocodone products both result from gradual but significant changes in the standards used for drug approvals.
In the case of pediatric over-the-counter medicines, the agency decided decades ago that drug makers could market the medicines for children even though they had only been tested in adults. Back then, it was assumed that children’s bodies were simply smaller versions of adult ones.
That assumption has proven untrue. Indeed, a growing number of studies suggest that cough and cold medicines work no better in children than placebos.
Despite this, there are 800 such products on the market and sales have long been strong. Most major pharmacies carry a dozen or more brands. The medicines are popular largely because children have an average of 6 to 10 colds each year, far more than adults.
Similarly, hydrocodone has never been shown to be safe and effective in children, and its dangers as a powerful and potentially addictive narcotic are clear. Even more broadly, 200 hydrocodone-containing products never won approval from the modern-day F.D.A.
There are thousands of such unapproved drugs on the market. Indeed, an estimated 2 percent of all prescriptions are written for unapproved products. Most have been around for decades, and the F.D.A. is gradually forcing their makers to either get official approval or stop selling them.”
While most patients put their faith in their physicians and pharmacists, it is important to always read the available literature with respect to potential side-effects and adverse reactions. It is also important to be aware of the proper indications for all drugs that you are taking since many problems are caused by drugs that are not needed in the first place. Be sure to remember that drugs often cause reactions that do not seem to be related to the medication when, in fact they are. If you, the patient, ever feel an adverse or even different effect after taking any medication, immediately consult a medical professional. It is better to be safe than sorry.
As always, the attorneys at Parker Waichman LLP are dedicated to bringing the public the most up-to-date information regarding pharmaceutical products, medical devices, toxic substances, and other consumer products with the potential to inflict serious injuries or death. If you or a loved one has suffered an injury (or death) that may be attributable to any product, do not hesitate to contact us at www.yourlawyer.com for a free and thorough case evaluation.