Letrozole warning true or false?(News)

American and Canadian fertility experts have expressed surprise and disappointment about new warnings concerning the aromatase inhibitor letrozole and its off-label use in fertility treatment.

"This is a knee-jerk reaction without a proper review of the data," said Dr. Kutluk Oktay, referring to the Swiss company Novartis Pharmaceuticals' letter to health care professionals in Canada and the United States warning that the drug may be associated with congenital anomalies. Letters also are planned for all other countries where the drug is available, said a company spokesperson.

Novartis markets letrozole under the name Femara for the treatment of breast cancer. But worldwide the drug is used off label for ovulation induction, and has replaced clomiphene citrate in many intrauterine insemination programs because of its superior pregnancy success rates and ability to decrease gonadotropin requirements. Additionally, it is one of the only safe options for breast cancer patients wishing to undergo in vitro fertilization with ovarian stimulation to freeze embryos prior to their cancer therapy.

Although Femara's label has always stated a contraindication in premenopausal women because of "the potential for maternal and fetal toxicity," Novartis' renewed concerns about the drug's use in fertility treatment arose after a small, unpublished Canadian study was presented at the recent conjoint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society, said company spokesperson Kim Fox.

Dr. Marinko M. Biljan, medical director of the Montreal Fertility Clinic, reported that among his patients, letrozole, used at the 5-mg dose for ovulation induction, was associated with an increased rate of serious fetal anomalies.

"We stopped using it at our center in September and we hope others will stop using it, at least at this dose," Dr. Biljan said in an interview.

An analysis of 150 babies born at his clinic after letrozole therapy (5 mg daily on days 3-7) found a 4.7% rate of major anomalies compared with a 1.8% rate in a control group of more than 36,000 babies born at a local "low-risk" hospital.