The Drug Technical Advisory Board (DTAB) sub-committee of the Union Health Ministry, which is re-examining the issue of whether the controversial drug letrozole should be allowed to be marketed for sub-fertility in young menstruating women in the country, has asked the promoter of the drug, Mumbai-based Sun Pharmaceuticals, to make a detailed presentation on the safety and efficacy drug. Besides, the sub-committee has asked for technical support from the Indian Council for Medical Research (ICMR).

According to sources, the sub-committee, headed by Dr Lakhbir Dhaliwal, head obstetrics & gynaecology, PGI Chandigarh, held another meeting in the first week of this month to discuss the issue. The meeting, attended by experts, company representatives and Drug Controller General of India (DCGI) Dr Surinder Singh, asked the Sun Pharmaceuticals to present a detailed presentation on the safety and efficacy drug.

It may be recalled that ever since the drug was given marketing approval by the DCGI, health experts have been raising eyebrows over the safety and efficacy of the drug in young menstruating women as its use in women of child bearing age is strictly prohibited elsewhere in the world due to severe side effects such as estrogen deprivation, ovarian atrophy, uterine atrophy, increased incidence of foetal malformations, foetal resorption and foetal death. The drug, a product of Novartis, was originally indicated for use in cases of breast cancer in postmenopausal women all over the world.

Besides, there was criticism from the medical fraternity that the DCGI has approved the drug on the basis of the phase-III trials conducted by Sun Pharmaceuticals on a mere 55 patients, that too conducted by private practitioners in personal clinics. They opine that these studies should have been conducted on more number of patients by independent, experienced investigators in large, research hospitals attached to medical college to avoid any bias results.

Experts are of the view that as per Drugs and Cosmetics Rules, even an old drug when used for a new indication is deemed to be a 'New drug' and must undergo a series of safety and efficacy studies both in animals and humans before its use in general public is allowed. If the drug is intended for use in young women of child bearing age, reproductive studies including fertility studies, teratogenicity studies and pre natal studies must have been performed in two female animals such as mouse, dog or rabbit.

Besides, the drug must also undergo phase I clinical trial in about 10 healthy volunteers (pre-menopausal women over 18 years of age) to determine the maximum tolerated dose and document preliminary side effects. Exploratory phase II studies to determine the therapeutic use, dose and safety of the drug are to be conducted in 10-12 patients in each of three to four research hospitals.

Experts regretted that none of the above studies were conducted by Novartis or any other company anywhere in the world since the drug was never intended to be used in women of childbearing age.