Lovenox

Recently issued precautions about congenital anomalies associated with Lovenox use in pregnancy should not dissuade doctors from prescribing the drug, but they should heed the warning not to use it in women with prosthetic heart valves, according to one expert.

Aventis, which manufactures the low-molecular-weight heparin (LMWH), sent a letter to health care professionals in February about additions to the drug's labeling information. According to the letter, congenital anomalies reported in infants born to women who received the drug during pregnancy include cerebral anomalies, limb anomalies, hypospadias, peripheral vascular malformations, fibrotic dysplasia, and cardiac defects. It also noted that a cause-and-effect relationship has not been established and that the incidence of these defects was no higher than in the general population.

The revised label also includes a warning that Lovenox (enoxaparin) is not recommended for use in patients with prosthetic heart valves because of an increased risk of valvular thrombosis.

But according to Dr. Charles Lockwood, the revised label should not prevent physicians from using the drug in most pregnant women. "There is no reason to change practice in any way except to avoid low molecular weight heparin in women with mechanical prosthetic heart valves," said Dr. Lockwood, professor and chair of obstetrics and gynecology at New York University, New York.

"The agent does not cross the placenta, providing no biological plausibility for such a risk. Secondly, a large study by Dr. J. Lepercq and associates [BJOG 108(1l):1134-40, 2001] described pregnancy outcomes in 604 women treated with enoxaparin and observed a congenital anomaly rate of only 2.5%. And lastly, the variety of anomalies reported by Aventis and their rare occurrence strongly suggests no specific malformation pattern or increased frequency," he said.

The American College of Obstetricians and Gynecologists has yet to issue an official position on use of LMWH in pregnancy and congenital defects but is considering the matter in detail, said Dr. Lockwood, chair of ACOG's Committee on Obstetric Practice.

A spokeswoman for Aventis in Bridgewater, N.J., said that the label revision was meant as "a precaution" and that the company is currently "in discussions to perhaps revisit the warning" and that "it might be toned down."

In the meantime, the revised label creates a "tremendous dilemma" for practitioners, said Dr. Philip Blatt, chief of hematology at Christiana Hospital in Newark, Del.

Pregnant women who need LMWH for either current or prior blood clots, recurrent miscarriage, or antiphospholipidantibody syndrome have few alternatives for treatment. "Coumadin [warfarin] is something we try not to use in pregnant women, and the advantages of low-molecular-weight heparin over standard heparin are significant. Some institutions have decided to use standard heparin in the first trimester and then switch back to LMWH. Whether this is an appropriate approach I don't know," Dr. Blatt said.

The advantages of LMWH over standard heparin, he said, are a 10-fold decreased risk of thrombocytopenia, a decreased risk of osteopenia, and much easier monitoring.

"Figuring out an appropriate dose is much more difficult with standard heparin than it is with LMWH," Dr. Blatt said.

"It has to be monitored and it's variable; those of us who did it a lot know it wasn't easy. If this turns out that this is what's required, I think that would be a big disappointment," he added.

There are two other low-molecular-weight heparins approved in the United States, dalteparin (Fragmin, manufactured by Pharmacia) and tinzaparin (Innohep, manufactured by DuPont Pharma Inc.). Spokespeople for both companies say there is no revised labeling for either product.

Labels on both agents say there are no adequate, well-controlled studies of the drug in pregnant women and that it should be used in pregnancy only "if clearly needed."

In addition, the Innohep label says "There has been one case each reported of deft palate, optic nerve hypoplasia, and trisomy 21 [Down] syndrome in infants of women who received Innohep ... during pregnancy. A cause and effect relationship has not been established."

The label also states that there have been four reports of fetal death/miscarriage in pregnant women receiving Innohep who had high-risk pregnancies and/or a history of spontaneous abortion. Approximately 6% of pregnancies were complicated by fetal distress. There have been spontaneous reports of one case each of pulmonary hypoplasia or muscular hypotonia in infants of women receiving Innohep during pregnancy. A cause-and-effect relationship has not been established.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group