Comparing Methotrexate Followed by Misoprostol to Misoprostol Alone for Early Abortion

Background/Rationale:

Medical abortions induced with either mifepristone or methotrexate and then followed by misoprostol are becoming more common. Although mifepristone is the preferred drug used to initiate the abortion in Europe, parts of Asia and in the US, it is not available in many parts of the world such as Canada, South America and most of Africa. While methotrexate is an acceptable and more widely available alternative, concerns about the safety of administration have discouraged some providers from using it. The cost of either mifepristone or methotrexate may also be barriers to widespread use. Misoprostol is inexpensive and easily available and is used alone for abortion both by the women themselves and by medical providers. Effective use of a single safe medication will reduce the number of medications women are exposed to.

Reported effectiveness rates for misoprostol alone in terminating pregnancies less than 8 weeks range from 64 to 94%, with varying doses and protocols. Use of misoprostol in early pregnancy is associated with an increased risk of Mobius syndrome in infants. For this reason, it is important that the most effective regimen is used for abortion to prevent failures.

A summary of the published protocols and results are as follows. A rate of 91.3% was found using 800 mcg vaginally every 24 hours for three doses, with higher effectiveness before 42 days gestation. A dose of 400 mcg sublingual misoprostol repeated every 24 hours for three doses resulted in 86% success. When mifepristone followed by 400 mcg misoprostol orally was compared to 800 mcg misoprostol vaginally, the effectiveness rate of the misoprostol alone was 88% and there were more prostaglandin side effects compared to the combined drug regimen. These side effects were reduced with prophylactic acetominophen and loperamide. Another centre reported a 90.8% effectiveness rate with two doses of 800 mcg misoprostol vaginally. One study assessed women after each dose of 800 mcg vaginal misoprostol and found that only 71.8% aborted after one dose and 92.1% aborted after multiple doses. When 800 mcg vaginally was repeated every 48 hours for three doses, an effectiveness rate of 93.6% was obtained. The same rate was obtained using 1000 mcg. When only 600 mcg vaginally was used, the effectiveness rate was only 64% repeating the dose every 8 hours did not improve the effectiveness. Similar rates were found for adolescents.

One proposed hypothesis for the 64-94% range in effectiveness between these various protocols is that sublingual misoprostol has a higher peak serum concentration than oral or vaginal misoprostol. In other words, the mean time to peak concentration for sublingual misoprostol is similar to oral misoprostol at 26 minutes and the area under the MPA curve is similar to moistened vaginal misoprostol.