Off label promotion and use of certain drugs had always raised some ethical debates amongst the medical fraternity and regulatory authorities for some time now. Yet, no regulatory authority of any country has ever taken a clear stand against this practice usually sponsored by pharmaceutical companies and some times by individual doctors themselves. Despite its inherent dangers and some stray benefits, the practice goes largely undetected by the authorities in most cases because of the secrecy associated with it. Pharmaceutical companies are keen in promoting off label use of a drug for the simple reason that if found successful the same drug could be marketed for another indication also. In 2003, some of the Indian pharmaceutical companies including Sun Pharmaceutical were found promoting letrozole for fertility treatment among infertile women by the office of the DCGI. The Novartis' drug was approved in India only for treatment of breast cancer. These companies were then warned against such off label promotion of the drug for the unapproved indication. Letrozole, developed by Novartis and sold under the brand name Femara, was approved in 1998 abroad as a treatment for breast cancer in post-menopausal women only. The drug inhibits the enzyme responsible for producing oestrogen. When administered to women of child-bearing age, it stimulates follicular development and could be exploited to induce ovulation.
It is rather strange to note that DCGI now found it alright to grant marketing approval for letrozole as an infertility agent. It may be true that the use of Letrozole as a fertility drug has been registered as an additional indication of a known drug. It has, therefore, undergone only phase III trials and skipped the phases that establish safety, determine side effects, dose and regimen. Under Section 122E(b) of the Drugs & Cosmetics Act, if a drug is found to have a new indication, it should be considered as a new drug and should be subjected to three phase clinical trials. But, if the dosage form is the same, the drug regulator can waive previous phases provided that drug safety is properly proven. DCGI seems to have gone for this option for granting the marketing approval. However, the toxicity information generated from cancer trials and contained in Novartis' prescribing information shows that Letrozole is embryotoxic and foetoxic. The MNC is thus right in issuing a warning to drug regulators worldwide in 2005 against the use of the drug for infertility treatment. The Union health ministry should have taken note of this alert and exercised adequate caution before granting the marketing permission for the new indication considering the fact that it is not a life threatening indication.