Last week, a leading newspaper in Mumbai flashed a report about the increasing use of Botox, a drug brand of Allergan Inc., for treating migraine and severe headaches in India. The report has quoted some of the top doctors from leading private hospitals in the city speaking about their experiences of administering the drug on patients obviously unaware of the fact that the drug is not approved for this indication anywhere in the world. The drug, botulinum toxin was first approved in 1989 by US FDA for treating eye muscle disorders and in December 2000 it was approved for treating cervical dystonia, a neurological movement disorder causing severe neck and shoulder contractions. In 2002, botulinum toxin Type A was further approved for treating severe frown lines between the eyebrows. There has been no approval for this drug for treating any other medical conditions so far. For treating migraine and severe headaches, clinical trials are still going on in the US and no results have been approved yet by the FDA. If this is the safety status of a drug like this, its off label use by doctors among the migraine patients is highly unethical and should be strictly disallowed. The fact is that Allergan is aware of such off label use of Botox in India. The company is morally bound to intimate drug authorities of such unapproved uses of this drug. Off label use of drugs on patients either with their knowledge or even without is an illegal activity indulged in by a number of medical practitioners in India and abroad. In some cases, pharmaceutical companies get directly involved in off label use by engaging a team of doctors for doing the job. The use of terbutaline for preventing premature labour by many doctors in the US is a well known case. The drug was originally approved by the US FDA for treating asthma. Similarly the use of certain epilepsy drugs by doctors in the US for treating depression, hot flashes and weight loss is reported to be very common. In India, unauthorized promotion of breast cancer drug, letrozole, for treating female infertility by certain companies three years ago, had already created a controversy after it was reported by Pharmabiz. DCGI then directed the companies to desist from such practices as these promotions amounted to violation of the section 122-E(b) of the Drugs and Cosmetics Rules.
Marketing approval for a new drug is granted based on evidence gathered from various pre-clinical and clinical evaluations for efficacy and safety against specific diseases for which the drug is indicated. The results are pertinent only for that disease condition and the trials delineate the dosage required for treatment, the frequency and duration of treatment. It is possible that adverse reactions may manifest when used by the particular population segment selected for the clinical trials. All these parameters change when the same drug is administered for treatment of a new indication, for which no data has been generated. Thus the treatment schedules, the dosage and the duration of treatment in off-label use could be very different from the approved schedules and such ad-hoc approaches could result in serious adverse reactions or may have even fatal outcomes. Testing for a new indication calls for fresh clinical trials and sometimes even repetition of toxicology studies to ensure that the doses used for the new indication do not result in toxic manifestations and adverse drug reactions.