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Multidose vs. Single-Dose Therapy in Ectopic Pregnancy


Am Fam Physician. 2003 Sep 15;68(6):1204-1211.

Approximately 2 percent of pregnancies in this country are ectopic, a condition that may cause significant hemorrhage and other serious complications. The success rates of medical treatment are comparable to those of surgery, with the added advantages of avoiding anesthetic and surgical risk while retaining fertility. Two protocols are currently used for medical treatment of ectopic pregnancy. “Single-dose”methotrexate therapy is given in a dosage of 50 mg per m2 of body surface area. The “multidose” regimen consists of 1 mg per kg of methotrexate, alternating with 0.1 mg per kg of leucovorin, for up to four doses of each agent. Both regimens are effective but have not been compared directly in a clinical trial. Barnhart and colleagues compared evidence for the efficacy and tolerability of single-dose and multidose regimens of methotrexate in the treatment of ectopic pregnancy.

Through electronic and manual searches, the authors identified 213 relevant articles, 26 of which met criteria for quality and inclusion in the analysis. They reviewed 1,327 cases of women with ectopic pregnancy who had been treated with methotrexate. The overall success rate of treatment was 89 percent, with 36 percent of women reporting side effects. In the single-dose group, 14.5 percent of women required more than one dose of methotrexate. In the multidose group, 53.5 percent received four or more doses. The overall success rate in the 1,067 women treated with the single-dose regimen was 88.1 percent compared with 92.7 percent in the 260 women treated with the multidose regimen. Side effects were reported by 31.3 percent of women receiving single-dose therapy and 41.2 percent of those receiving the multidose regimen. Rates of hospital admission were similar in the two groups (12.4 percent for single-dose therapy and 11 percent for multidose therapy).

The authors conclude that although the multidose regimen of methotrexate is associated with significantly more side effects and is more complicated to administer, it is more effective than the single-dose protocol for treatment of unruptured ectopic pregnancy. Because unsuccessful medical treatment could result in hemorrhage, emergency surgery, or even death, the additional efficacy of multi-dose treatment outweighs the greater convenience and lower rate of side effects associated with single-dose treatment.

Barnhart KT, et al. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol. April 2003;101:778–84.



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