A popular anti-ulcer pill used around the world for inducing labor and preventing post-delivery bleeding appears to be as effective as more expensive drugs but still must be used with caution, according to an updated systematic review of studies.
The pill -- a prostaglandin known generically as misoprostol and sold as Cytotec -- is used primarily for treatment of peptic ulcers and is not approved for use in pregnant woman in most countries, including the United States. However, because of the convenience of oral dosing compared to standard vaginal or cervical treatments to speed delivery, "off-label" use is common in many countries
"Due to the limited evidence about the safety, oral misoprostol should be used with caution for the induction of labor," said authors Dr. Zarko Alfirevic and Dr. Andrew Weeks, both obstetricians at England's University of Liverpool.
Legal liability, as well as safety concerns, make use of misoprostol problematic "because of a relatively high rate of uterine hyperstimulation and the lack of appropriate dose ranging studies," they said.
However, the authors acknowledged that other approved drugs are expensive and must be refrigerated, whereas misoprostol is relatively cheap and can be stored at room temperature. Off-label use is thus especially attractive in developing countries and is likely to continue.
"In those situations, clinicians should use as low a dose as possible and report serious adverse outcomes," say the authors. They recommend a maximum dose of 50 mcg. Higher doses could lead to tearing of the uterus, which could be life-threatening to both mother and fetus.
The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
It is an update of a 2001 Cochrane review, comprising more than twice as many studies.
The history of misoprostol use for induction of labor in full-term pregnancies has been complicated by the fact that the drug is also used for termination of first-trimester pregnancies, routinely used in combination with RU-486, the so-called "morning after" abortion pill.
Alfirevic said that despite the safety, legal and political issues surrounding misoprostol, "Clinicians felt that they had a duty to investigate this drug because this is the only prostaglandin that could be used effectively orally. It could potentially be a lifesaving drug in developing countries, where they didn't have access to any safe drug for abortion, induction of labor, or prevention of post-partum hemorrhage."
Nigeria this month became the latest country to approve its use to induce labor, a procedure recommended when carrying a pregnancy is riskier than giving birth.
The updated review included 41 randomized trials -- 28 of them new since the previous study -- and involved 8,606 women. The studies compared misoprostol administered orally versus vaginally and compared oral misoprostol with vaginal use of the prostaglandin dinoprostone and with intravenous oxytocin. The review concluded that oral misoprostol "appears to be at least as effective as current methods of induction."
Although the authors found no evidence of serious problems among the participants, Alfirevic warned that "much more data are needed before we can be confident that there are really no adverse fetal effects that can be attributed to misoprostol." To address the risks of rare adverse outcomes, studies would need to include in excess of 30,000 women, the authors said.
Use of oral misoprostol by American obstetricians is likely to remain relatively stable for the foreseeable future, predicts Dr. Deborah Wing, a specialist in maternal fetal medicine at the University of California, Irvine. "Because of the highly litigious nature of medical practice in the United States, there are practitioners that have grave concern about the use of the medication without FDA labeling."
Still, Wing envisions a day when, in appropriate circumstances, a safe and effective regimen of oral misoprostol can be prescribed on an outpatient basis around a woman's due date. "What woman wouldn't want to be able to take a pill to control when she went into labor?" she asks. "But we're a long way away from that."
The review itself noted that "most studies -- did not assess women's views or satisfaction rates" regarding induced labor versus possible safety risks.
Alfirevic is one of the principal investigators of a trial included in this review. He and Weeks have both served as advisers or investigators for companies involved in the development of misoprostol products for labor induction, and Weeks runs the Web site www.misoprostol.org that advocates its use.
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