Andrew von Eschenbach, M.D., Commissioner
US Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Dear Dr. von Eschenbach:
I urge you to immediately stop the illegal and dangerous promotional campaign by Ortho-McNeil Janssen-funded researchers for the unapproved use of Topamax (topiramate) for treating alcoholics (the drug is only approved for treating seizure disorders and migraines).
In a study to be published in tomorrow’s Journal of the American Medical Association, funded entirely by the company, researchers from the company and from the University of Virginia find only a modest improvement in the percentage of days of heavy drinking in people using Topamax compared with people using a placebo. Both groups also got a weekly 15 minute intervention by a trained nurse to promote compliance.
But accompanying the study, in an embargoed press kit distributed by the University of Virginia on behalf of the researchers, is a question and answer sheet asking “Can my doctor prescribe me topiramate for alcohol dependence?” The answer is, essentially, yes: “Since topiramate is currently FDA-approved for seizures and migraines, it is available to your doctor to prescribe it to you off-label.” This clearly violates the prohibition on off-label promotion, as patients are being explicitly urged/promoted to ask their doctor for topiramate to treat their serious alcohol addiction.
Not only is this off-label promotion illegal but it is also potentially dangerous. The “Patient Package Insert” portion of current FDA labeling for the approved uses of the drug states, in a section entitled “What Should I Avoid While Taking Topamax?”, “You should avoid drinking alcohol while taking Topamax. Alcohol with Topamax can make side effects such as sleepiness and dizziness worse.”
Indeed, the data from this study showed a statistically significantly increased incidence of dizziness (doubled) and difficulty with concentration/attention (quadrupled) in patients getting topiramate compared to patients getting a placebo, even though both groups were still drinking quite heavily by the end of the study.
It is not the research or the publication of the study that is illegal but the promotional material that goes beyond the research to solicit new sales for the drug. The reason why FDA laws and regulations prohibit such off-label promotion or advertising is that in the absence of evidence of benefits and risks for treating a specific medical condition, patients, doctors and the FDA cannot determine if the benefits outweigh the risks.
Other serious side effects of Topamax described in the FDA-approved patient information for the drug include:
- Metabolic acidosis. Metabolic acidosis is a condition that happens when there is too much acid in your blood. Metabolic acidosis can cause symptoms such as tiredness, loss of appetite, irregular heartbeat, and impaired consciousness.
- Eye problems. Serious eye problems include: a sudden decrease in vision (acute myopia) with or without eye pain and a blockage of fluid in the eye causing increased pressure in the eye (secondary angle closure glaucoma). Call your healthcare professional right away if you have a loss in vision or get eye pain. These problems can lead to blindness if not treated right away.
- Decreased sweating (oligohidrosis) and increased body temperature (fever). Patients, especially children, should be watched closely for signs of decreased sweating and fever (increased body temperature), especially in hot temperatures. Some patients may need hospital treatment for this condition.
- Kidney stones. Drink plenty of fluids when taking Topamaxto decrease your chances of getting kidney stones.
- Tingling of the arms and legs (paresthesia) is a common side effect of Topamax.
Unless the FDA promptly orders the end to this illegal promotional campaign, the message to the pharmaceutical industry is that “you can sell more drugs and possibly injure more people by promoting off-label uses whose benefits have not been proven to outweigh their risks. And, don’t worry, we will not stop you.” Such reckless disregard for Federal law and regulations should not be tolerated.
Sidney M. Wolfe, M.D.
Health Research Group of Public Citizen
 Heavy drinkers were defined as men who regularly drank 5 or more (women 4 or more) drinks per day. After 14 weeks of treatment, the percentage of heavy drinking days was still 43.8% for people getting the drug and was 51.8% for those getting the placebo. At baseline, 82% of the days for both groups involved heavy drinking so the improvement caused by the trained nurse intervention alone-as seen with the placebo group-was much more effective than the difference attributable to the drug.
 The FDA regulations, 21 CFR sec 202.1(e)(6), titled Advertisements that are false, lacking in fair balance, or otherwise misleading, states “An advertisement for a prescription drug is false, lacking in fair balance, or otherwise misleading, or otherwise violative of section 502(n) of the act, among other things, if it: . . . (xi) Uses literature, quotations, or references for the purpose of recommending or suggesting conditions of drug use that are not approved or permitted in the drug package labeling.” The prohibition also follows from the requirement in the law, 21 USC sec 355, that a drug cannot be marketed until it is approved, and that the approval is [only] for the uses set forth in the labeling. The FDA has previously prohibited off-label promotion for drugs even if it did not take the form of advertisements.