The safety of misoprostol

Abstract

TITLE: The Safety of Misoprostol AUTHOR: Anke Hemmerling, MD, MPH Bixby Fellow of Population and International Health University of California, Berkeley School of Public Health 513 Warren Hall Berkeley, CA 94720-6390 Email: anke@berkeley.edu Misoprostol, Safety, Post Partum Hemorrhage KEYWORDS: Misoprostol is currently on the WHO Essential Drug List for treatment of gastric ulcers, for induced abortion in combination with mifepristone, and more recently for induction of labor. The WHO will review its role as an essential drug for control of post partum hemorrhage (PPH) in early 2007. Relevant data on the safety of misoprostol has been accumulated since the introduction of the drug in the late 1980s. Since then, millions of individuals worldwide have used up to four tablets (800 mcg) daily for treatment and prevention of gastric ulcer. Multi-center trials following thousands of users [1, 2], as well as a review of the worldwide safety data [3] and a Cochrane Review in 2002 [4] failed to report any misoprostol related deaths or side effects severe enough to demand the cessation of treatment. Common side effects for long term misoprostol users with gastric ulcers were the same as seen in some women treated for PPH – and include chills, fever, diarrhea and nausea. Four cases of acute toxicity after accidental or intentional overdose with misoprostol are described in the peer-reviewed literature, two of them in women beyond 30 weeks of pregnancy. [5-8] After ingesting a large number of misoprostol tablets, sometimes mixed with other medication, tachycardia, nausea and abdominal pain and, in some cases, hyperthermia was reported, although the authors of these reports emphasize the complete resolution with supportive care within 12 hours. Bentov [7] concludes that his case of overdose with 42 tablets (8.4 mg) over three days “illustrates the relative safety of the drug”. The literature also reports one case of severe hyperthermia post partum reaching 41.9 C following a normal dose of 800 mcg of oral misoprostol and requiring intensive supportive care. [9] Although no other extreme cases of severe hyperpyrexia are reported, several studies on PPH using oral misoprostol of 400-600 mcg describe transient pyrexia of 38 degrees Celsius