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Statement by Sidney M.Wolfe, M.D. Director, Public Citizen?s Health Research Group Concerning Petition to Require FDA to Start Regulating the Content of Patient Information Leaflets for Prescription Drugs

Statement by Sidney M.Wolfe, M.D.
Director, Public Citizen?s Health Research Group
Concerning Petition to Require FDA to Start Regulating the
Content of Patient Information Leaflets for Prescription Drugs
June 9, 1998

A substantial proportion of the estimated 100,000 Americans who die each year because of adverse drug reactions and the serious injuries to 2.2 million others which involve hospitalization could be prevented. One of the most important ways of preventing such tragedies is to ensure that patients are adequately informed about the risks and proper use of prescription drugs. As long ago as 1979, FDA stated that: “. . . oral communication of information about prescription drug products by health professionals cannot be relied upon to provide patients with the information they need to use prescription drug products properly.” More recently, the Agency said: “Inadequate access to appropriate patient information is a major cause of inappropriate use of prescription medications, resulting in serious personal injury and related costs to the health care system.”

The most recent survey by FDA, published last year, found that only a minority of the 1000 people interviewed by researchers reported that their physicians told them about the precautions or adverse effects of the drugs they were prescribing for them. Concerning precautions about the drugs, only 35% were informed by their physicians and only 33% were told about adverse effects. Although some patients also reported that they received counseling about their prescription drugs from their pharmacists–and many of these probably also had received information from their doctors–it is clear from this important study that a large proportion of patients do not receive any oral information about precautions (at least 40%) or adverse effects (at least 48%) from either their physician or pharmacist.

Public Citizen, a nationwide organization representing 120,000 consumers, and Patricia and Ben Christen, whose only son Cory died as a result of unregulated, misleading, commercially produced written patient drug information, hereby petition the Food and Drug Administration (FDA), pursuant to the Federal Food, Drug and Cosmetic Act, to immediately recall, or seize if necessary, unregulated information that is being distributed with prescription drugs that is not consistent with or derived from a drug?s FDA approved, regulated professional product labeling, commonly known as the package insert. A large proportion of the patient information leaflets (PILs) produced by commercial information vendors and distributed by pharmacists to millions of consumers when prescriptions are dispensed may contribute to thousands of drug injuries and deaths by giving the public a dangerously false sense of security about the safety of prescription drugs by failing to warn about adverse reactions or proper use including dangerous dosages. FDA?s first priority should be to take action by recalling those PILs whose inaccurate information is most likely to cause substantial harm if not corrected.

Seven-year-old Cory Christen?s death, from a drug-induced cardiac arrhythmia, was needless and preventable and is directly attributable to his parents being deprived of vital dosing and adverse reaction information, information that was omitted from a PIL produced by an unregulated commercial information vendor, Medi-Span, Inc. of Indianapolis, for the antidepressant drug imipramine (Tofranil). In addition to this tragic example, the FDA is in possession of other evidence demonstrating that dangerous informational deficiencies exist in the PILs for other drugs.

Forty-one thousand patients are hospitalized and an estimated 3,300 die each year from gastrointestinal bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs), used for treating arthritis or pain.Fall 1990: 114-122. Studies have shown that if patients are not adequately informed to stop the use of such drugs if they develop abdominal pain and therefore do not identify the pain as an adverse reaction to the NSAID, they are much more likely to have serious bleeding sufficient to require hospitalization. Given that many physicians do not routinely provide this kind of information to their patients, the routine use of accurate and complete PILs would save hundreds of lives lost to NSAID-induced gastrointestinal bleeding and thousands of hospitalizations. As discussed below, FDA?s own study has shown serious deficiencies in PILs and a recent Public Citizen?s Health Research Group survey of PILs for 15 NSAIDs found that only a small fraction warned patients to stop using the drug if they developed abdominal pain.

This petition is based on the following which will be discussed in greater detail:

  • The FDA has the clear legal authority to regulate all information distributed with a prescription drug, including commercially produced PILs.
  • The needless death of Cory Christen could have been prevented if critical safety information had not been omitted from an unregulated PIL for the drug imipramine (Tofranil and generics). If Cory?s parents had been given an imipramine PIL that was consistent with or derived from the drug?s approved product labeling they would have known four critical pieces of information, any one of which might have saved the life of their son:

(A) That imipramine can cause heart rhythm disturbances that are potentially fatal.

(B) That the imipramine prescribed for their son was for an “off-label” use, a use that was not approved by the FDA. Imipramine is approved only for depression and pediatric enuresis (bed wetting), not ADHD.

(C) That Cory had been prescribed a dose of imipramine that was 3.5 times greater than the maximum dose recommended for children in the imipramine approved product labeling.

(D) That the hallucinations and tremors experienced by Cory were actually adverse drug reactions.

  • An FDA survey of PILs has found substantial differences between commercial information vendors in the quality of information provided including the omission of warnings which could be life-saving. Drugs involved included the tranquilizer alprazolam (Xanax), antibiotic amoxicillin and high blood pressure/heart failure drug enalapril (Vasotec).
  • Two studies conducted by Public Citizen?s Health Research Group have shown that PILs distributed by pharmacists are incomplete with regard to safety information. An important, possibly life-saving instruction in the FDA-approved labeling was to tell patients to stop the NSAID and contact the prescriber should symptoms of GI toxicity (such as abdominal pain) appear. Only 15 out of 59 (25.4%) patient information leaflets (involving 18 different NSAIDs) warned about stopping the drug if symptoms of GI toxicity such as abdominal pain occur. Other drugs with dangerously incomplete or misleading PILs which we have obtained include bromocriptine (Parlodel), short-acting nifedipine (Adalat, (Procardia), the pain-killer tramadol (Ultram) and the antibiotic ciprofloxacin (Cipro).
  • Patients who are informed of the risks of a prescription drug and are told what steps to take should an adverse drug reaction occur reduce their likelihood of suffering the most serious consequences of an adverse drug reaction.

In summary, voluntary self-regulation by the warnings companies such as Medi-Span, Inc. has proven to be unsuccessful. Companies selling these warnings are willing to omit information about deadly adverse effects resulting in inadequately-educated patients who are therefore less reluctant to use or question their prescribed medications. Medi-Span, Inc. has testified through its vice-president of operations, that it allowed the warnings. Several marketplace to help determine the content of its documents attributable to Medi-Span, Inc. indicate that the Medi-Span, Inc. monographs (PILs) are intended to “stand alone” in the absence of counseling, and are considered a safety net in terms of risk management. The dangerously deficient sheets demonstrate the dangers of not requiring scientifically-based regulation: In claiming that “no consistently inferior product would survive in the marketplace”, a company abdicates even its voluntarily-assumed responsibility to “insure accuracy”. The marketplace should not judge the quality of these items; scientists should. It is time for FDA to exercise its legal authority and start regulation of the content of patient information leaflets used by hundreds of millions of people like the Christens. There is little questions that the lives of thousands or more people like their son Cory could be spared if patients were aware of information neither their doctors nor pharmacists are regularly informing them of.

1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998;279:1200-05.

2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. JAMA 1998;279:1200-05.

3. Department of Health and Human Services. Food and Drug Administration. Prescription Drug Product Labeling; Medication Guide Requirements. Federal Register Vol. 60, No. 164, Thursday, August 24, 1995.

4. Morris LA, Tabak ER, Gondek K. Counseling patients about prescribed medication. Medical Care 1997; 35: 996-1007.

5. Ray WA, Griffen MR, Shorr RI. Adverse drug reactions and the elderly. Health Affairs Fall 1990: 114-122.

6. Sasich LD, Wolfe SM. Deficiencies in patient information leaflets concerning gastrointestinal complications of nonsteroidal anti-inflammatory drugs. Journal of General Internal Medicine 1997;12(suppl):79[abstract].

7. Wynne HA, Long A. Patient awareness of the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). British Journal of Clinical Pharmacology 1996;42:253-256.