POSSIBLE BIRTH DEFECTS WITH THE CANCER DRUG LETROZOLE (FEMARA) WHEN USED FOR INFERTILITY

December 2, 2005

Health Canada, the Canadian equivalent of the Food and Drug Administration (FDA), warned physicians on November 17, 2005 about reports of birth defects in the infants of mothers prescribed letrozole (FEMARA) for the treatment of infertility. Letrozole is approved only for the treatment of breast cancer and is now contraindicated (it should not be used), in women before menopause.

The full text of the warning is available on the Health Canada Web site at: www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/femara_hpc-cps_e.html.

The use of letrozole to induce ovulation in the treatment of infertility is an unapproved, or an off-label, use of the drug. When drugs are prescribed off-label patients may be on dangerously thin ice as there is often inadequate scientific evidence to know whether the drug is either safe or effective for the treatment of an unapproved use.

Unfortunately, in most of these circumstances, patients are not told by their physicians that they are being prescribed a drug that has not been shown to be safe and effective. Patients who are prescribed drugs for unapproved uses are, in essence, unwitting subjects in an uncontrolled experiment in which they have been not been given their right of informed consent. Furthermore, no one is collecting data on outcomes.

The U.S. professional product labeling, or package insert, for letrozole warns that the drug may cause fetal harm when it is given to pregnant women and that women should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy.

Studies done in pregnant rats given letrozole during the period when organs are forming showed that the drug was dangerous to the embryo and the fetus. Damage to embryo and fetal health was seen with doses as low as 1/100 the daily maximum recommended human dose. Novartis, the manufacturer of letrozole has admitted that they have found 13 reports of pregnant women receiving the drug worldwide, contrary to its warning label against use in pregnancy. Of those 13, at least two had miscarriages and two had children with birth defects

The U.S. professional product labeling for letrozole can be found at:www.femara.com/pdf/full_pi.pdf .

Unfortunately, letrozole is widely discussed on the Internet as an infertility treatment. An example appears on Aetna’s web site, Aetna InteliHealth (Aetna is a very large insurance company that advertises itself as a "trusted source" of drug information) yet this site advises women that Femara is used to induce ovulation and "may be better" than another drug approved for this purpose and does not mention that the use of the drug to treat infertility is not approved and that fetal harm may occur with the use of the drug in premenopausal women. InteliHealth’s comments on letrozole for the treatment of infertility can be found on the Internet at: www.intelihealth.com/IH/ihtIH/WSIHW000/9032/24519/417705.html .

What You Can Do

If you are seeking treatment for infertility and the prescribing physician recommends letrozole, you should ask her/him to recommend other treatments.The effectiveness of this drug in treating fertility has not been clearly established.