NEW YORK (Reuters Health) – The dose of misoprostol given after mifepristone for termination of early pregnancy should stay at the recommended dose rather than be lowered, a multicenter study shows.
The researchers note in BJOG online June 18 that a regimen of 200 mg mifepristone followed 36-48 hours later by 800 mcg misoprostol administered vaginally is recommended by the World Health Organization and other bodies for terminating pregnancy up to 7 weeks. However, some small studies have found that a misoprostol dose of 400 mcg is effective, while others have reported that tablets can be administered sublingually or buccally.
“Thus, we wished to study: 1. how sublingual administration of misoprostol compares to vaginal administration in efficacy and side-effects; and 2. how 400 mcg of misoprostol compares to 800 mcg misoprostol when administered using these two routes,” lead author Dr. Helena von Hertzen explained in an email.
The international team compared the efficacy of the two misoprostol doses given 24 hours after mifepristone in a trial involving over 3000 women in a dozen countries. “We used the interval of 24 hours which we had found to give a similar efficacy with less side effects than the 36-48 h interval,” noted Dr. von Hertzen, who was with the World Health Organization in Geneva, Switzerland at the time of the trial, and is now with Concept Foundation, Geneva.
The results indicated that the risk of incomplete abortion was significantly higher (p<0.01) at 9.5% with the 400 mcg dose of misoprostol than with the 800 mcg dose (5.8%), regardless of route of administration.
“The noninferiority of 400 mcg misoprostol was not demonstrated for failure of complete abortion, since the 95% CI (confidence interval) for the risk difference crossed the margin of noninferiority of 3% (difference: 3.7%; 95% CI 1.8–5.6%),” the researchers report.
The proportion of women reporting adverse symptoms such as nausea and pain was similar in each arm of the study up to the time of misoprostol administration. Thereafter, however, these symptoms were more frequent with the 800 mcg dose and with sublingual administration.
The authors conclude that “400 mcg misoprostol should not replace 800 mcg when administered 24 hours after mifepristone pretreatment to induce abortions up to 63 days’ gestation.”
Dr. von Hertzen added, “Misoprostol is not an expensive drug, so even financial aspects do not support the use of the lower dose.”
Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial