Am Fam Physician. 2004 Jan 15;69(2):400.
Severe postpartum hemorrhage, the most common serious complication of delivery, traditionally is managed by blood transfusion or surgery. Oral misoprostol has been advocated as an effective and acceptable therapy. Misoprostol has significant uterotonic properties. Its most common adverse effects are shivering and pyrexia. In certain circumstances, rectally administered misoprostol can be lifesaving. The use of this administration route is increasing worldwide, but the pharmacologic characteristics of rectal misoprostol may not be equivalent to those of oral misoprostol. Khan and El-Refaey studied the pharmacokinetics and side effects of misoprostol administered rectally during the third stage of labor.
To assess the absorption of misoprostol, they studied 20 women in spontaneous labor of a singleton term fetus at a teaching hospital in London. The mothers were older than 18 years and had no contraindications to prostaglandin therapy. The patients were randomly assigned to receive 600 mcg of misoprostol orally or rectally as soon as the umbilical cord was clamped. The study could not be blinded as to treatment allocation. The third stage of labor was managed in the normal manner for the institution with the exception that blood samples were drawn from an intravenous cannula at baseline and at 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes after administration of the drug.
To assess side effects, 275 mothers were similarly randomized to receive rectal misoprostol in one of two doses (400 mcg [n=91] or 600 mcg [n=92]) or oral misoprostol in a dose of 600 mcg [n=92]. The mothers were monitored for pyrexia, vomiting, and shivering. Oral temperature was recorded before delivery and after 20, 40, and 60 minutes. Vomiting and shivering were assessed by the birth attendant and the patient on a self-assessment questionnaire.
The two groups of patients were well matched in both studies. The mean maximum plasma concentration of misoprostol was significantly lower (statistically significant) when administered rectally (184 pg per mL compared with 327.9 pg per mL), and this maximum concentration took an average 23 minutes longer to achieve when the drug was given rectally. The profiles of the serum concentrations achieved by the two routes of administration were quite different. Oral administration resulted in a rapid peak in an average of 18 minutes, followed by a steep decline in 60 minutes. When administered rectally, the mean maximum concentration was achieved at 40.5 minutes and declined slowly in one half of the patients. Temperatures rose in all women after delivery, but the average rise was significantly greater (statistically significant) in those treated with oral misoprostol.
Fevers of more than 38°C (100.4°F) were recorded in eight of 92 mothers treated orally, and in three of 183 treated rectally. Shivering after delivery was recorded in 76 percent of patients treated orally, 54 percent of those treated with 600 mcg rectally, and 56 percent of those who received 400 mcg rectally. The groups did not differ in vomiting or use of analgesia following delivery.
The authors conclude that rectal administration of misoprostol is associated with fewer side effects but results in lower peak levels and a different plasma concentration profile than oral administration. As rectal misoprostol becomes more widely used in the management of the third stage of labor, the authors suggest that higher doses administered rectally may be necessary to achieve efficacy without the disadvantages of the oral or vaginal routes.
Khan RU, El-Refaey H. Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor. Obstet Gynecol. May 2003;101:968–74.
Copyright © 2004 by the American Academy of Family Physicians.
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