Saturday, December 10, 2005

The Femara Scare (Now Resolved!)
(Read all way to bottom of article)

Femara (letrozole) has been widely used off label in the recent years for ovulation induction by fertility doctor nationwide.
News Media have been reporting that the

Swiss drug manufacturer Novartis is sending letters to fertility doctors worldwide to reiterate a warning that the drug should not be given to women who may be pregnant, said spokeswoman Kim Fox.

The U.S. label on the drug already warns that it has been associated with birth defects, but concerns arose when a researcher in Canada published a report noting cases where the drug had been given to pregnant women.

Here is the abstract of the report presented at the conference

[O-231] The Outcome Of 150 Babies Following The Treatment With Letrozole Or Letrozole And Gonadotropins.

M. M. Biljan, R. Hemmings, N. Brassard. Montreal Fertility Centre, Montreal, PQ, Canada; St'Mary's Hospital, Montreal, PQ, Canada; Université Laval, Québec, PQ, Canada

Objective: Letrozole is a medication widely used for secondary breast cancer prevention. Recently, this aromatase inhibitor has been used for ovulation induction. In this analysis we report the outcome of 150 babies born as a result of treatment with either letrozole alone or a combination of letrozole and gonadotropins at the Montreal Fertility Centre. Design: Retrospective analysis. Materials and Methods: This analysis includes patients with unexplained infertility and patients with polycystic ovarian disease. As a control group we used patients delivered at “St. Mary’s” hospital in Montreal between 1995 and 2004. The choice of the hospital was deliberate, as “St. Mary’s” hospital delivers mostly low risk babies. Results: During a period of 25 months 171 babies were born as a result of the use of letrozole or letrozole and gonadotropins. Twenty one babies were lost for follow-up. One hundred and fifty babies were compared with a data-base of normal deliveries containing 36,050 deliveries. The median age (M) of treated patients was 35.2 years (interquartile difference (IQD)= 31.4-37.9). We had 110 singleton and 20 twin pregnancies. All twin pregnancies apart of one were conceived following the treatment with letrozole and gonadotropins. The incidence of vaginal bleeding was 36.7% in the first trimester, 7.3% in the second trimester, and 1.3% in the third trimester. Seventy-seven non-diabetic singleton pregnancies were delivered at term. There was no difference in weight between this group and the control. Twenty patients had gestational diabetes. Seventeen patients with gestational diabetes delivered at term. When compared with controls these babies were of a significantly lower birth weight than controls (p<0.002 ci="11.3-136.6)." p="0.25" ci="0.78-4.71)." p="0.0005" ci="2.64-27.0)" p="0.0006" ci="3.30-58.1)">

Although this finding needs to be taken very seriously we need to review the data. this is only an abstract and it is not clear from the abstract what the specifics are about the cardiac and locomotor malformations. Also remember that this is a retrospective study.
I am a bit puzzled by the fact that it is known that Femara has a half life of 2 days so all of it should be out of the body by the time a pregnancy is established therefore there is no clear biological reason on why any effect should be seen .

A Follow Up to This study was announced in 2006 and reversed the findings

Concerns about the use of letrozole, an easy-to-use and inexpensive drug for the treatment of infertility, appear to be unfounded, according to a major study co-authored by Dr. Togas Tulandi, Director of the Division of Reproductive Endocrinology and Infertility, McGill University Health Centre (MUHC), Chief of Obstetrics and Gynecology at the Jewish General Hospital and professor of obstetrics and gynecology at McGill University. The findings, which are currently available in an early online edition of Fertility and Sterility, showed that babies whose mothers were treated with letrozole had the same rate of birth defects as those whose mothers were treated with clomiphene citrate — the low-risk, first-line treatment for infertility for more than 40 years.

"We found no statistically significant difference in the overall rates of major and minor malformations or chromosomal abnormalities between newborns in the two groups," says Dr. Tulandi. "Our findings indicate concerns about a link between letrozole and birth defects are unfounded. This is significant because it confirms that letrozole can indeed be used in the treatment of infertility without increasing risk to the fetus."

The study contradicts an earlier, much smaller study linking letrozole to increased rates of inherited malformations. This study led to widespread concern about the use of letrozole, a drug which has been widely used in the treatment of infertility in recent years.

"There were several methodological problems with the earlier study," says Dr. Tulandi. "For one thing, it compared the incidence of birth defects in children conceived spontaneously with that in children conceived through fertility treatments using letrozole. This is an apples-and-oranges comparison, because there are always fewer birth defects in children conceived spontaneously." The earlier study also compared different age groups between the control and treatment.

The new study, by Dr. Tulandi, Dr. Robert Casper from the Department of Obstetrics and Gynecology at the University of Toronto, and their co-authors examined a total of 911 babies whose mothers were treated for infertility with either letrozole or clomiphene citrate from 2001 to 2005. Five Canadian centres in Quebec and Ontario participated.
(adapted from Press Release)

Letrozole is currently back in my practice!

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