The office of the Drugs Controller General of India (DCGI) has sought explanation from Mumbai based Sun Pharmaceuticals for allegedly promoting its branded letrozole (Letroz) for unapproved indications.

The official notice was served on the basis of the media reports on the attempts of Sun Pharma to promote Letroz, an expensive anti-cancer drug as an infertility drug. Letroz is marketed through Inca Specialties, a division of the company. The company is also having the same drug marketed under a different brand name "Letoval", by Spectra, yet another division of Sun Pharmaceuticals. The company is possessing DCGI approval to market Letrozole as a breast cancer drug for menopausal women.

According to official sources, the drugs control department was aware of its "off label" use by the doctors for treating infertility. "There is nothing unlawful in the off label use of drug as it's the right of the concerned doctor to do so," they said.

However, Sun Pharma has been found disseminating printed material promoting the unapproved use of the drug. The officials agreed that the company's involvement was tantamount to conducting clinical trials on unsuspecting patients and needed prior DCGI approval. "We are looking forward to receive their response," they informed.

As per the D&C Act, if a drug cleared for a specific disease is to be used for a new disorder, the drug is considered a "New Drug" (as defined in Rule 122-E in the Drugs and Cosmetics Rules) and needs fresh government approval after undergoing a series of tests and trials, both in animals and humans. Only then can it be marketed and promoted for a new disorder. No such trials have been undertaken on letrozole's use as a fertility agent.
While the drug control officials regard the "off label" use as harmless, studies conducted abroad have shown that letrozole invites serious side effects in the patient.
According to medical experts, "Animal studies using as little as 0.003mg/kg (about 1/100th of normal human per kg dose) have shown that letrozole is both embryotoxic as well as fetotoxic as indicated by intrauterine mortality (death within uterus), increased resorption (destruction of fertilized egg), increased postimplantation loss, decreased number of live foetuses and foetal abnormalities including absence and shortening of renal papilla (a part of kidney), dilation of ureter (urinary passage), oedema and incomplete ossification of frontal skull and metatarsals (small bones of feet). Letrozole is teratogenic (malformation of babies); even at minuscule doses of 0.03mg/kg (about 1/10th of normal human per kg dose) causing foetal domed head and cervical vertebral (neck bones) fusion."

According to them the side effects of letrozole are grave and include ovarian tumours, liver cancer, hyperplasia of ovaries, sexual inactivity, atrophy of the reproductive tract. Other adverse reactions are hot flushes (19% cases), high blood pressure (8% cases), bone pain (22%), back pain (18%), joint pain (16%), limb pain (10%), breathlessness (18%) and cough (13%). The drug can also cause thrombosis (clot formation), life-threatening pulmonary embolism (clots in the lungs), heart attack, angina, stroke and paralysis.