Background

• is inexpensive (US$.36 per 100 mcg);

• is easily stored (shelf life 7 years);

• has, in comparison with other prostaglandins, minimal effects on cardiovascular and bronchial tree smooth muscle (can be safely used in hypertensive patients and asthmatics);

• is not affected by ambient temperature; and

• needs no refrigeration, needles or syringes for its storage and administration.

Mechanism of Action

Source: El Refaey et al 1995.

It is assumed that rectal administration results in a similar profile. Vaginal dosing therefore can take place with longer intervals than oral dosing for similar desired uterine effect, and accumulation above "safe" levels with undesirable side effects can take place. With oral and vaginal dosing of up to 400 mg every 8 hours, no accumulation has been noted and no accumulation has been seen with a maximum of three doses of 400 mcg 3 hours apart. Potential hypertonus as a result of drug accumulation could lead to:

• uterine rupture in the second or third trimester,

• fetal distress in the third trimester, and

• high rates of nausea and diarrhea in all trimesters.

For obstetrical use, the vaginal application has been studied the most. Misoprostol in the first and second trimesters is an effective pregnancy termination agent either as a single agent or as an adjunct to methotrexate or mifepristone. Misoprostol will effectively dilate the cervix prior to surgical abortion. Misoprostol has been studied as a cervical ripening and induction agent in the last two trimesters. Its use as an alternative to MVA or suction curettage for management of incomplete abortion (first trimester), as a uterotonic agent in the active management in third stage and as a treatment of postpartum hemorrhage are currently being studied.

Misoprostol offers a potentially inexpensive treatment for life threatening bleeding in pregnancy in developing countries in the hands of frontline healthcare workers.

Research Results

• Fong et al (1998) demonstrated that 400 mcg vaginal misoprostol will dilate the cervix to more than 8 mm in 96.7 percent of patients when it is given up to 3 hours or more prior to suction curettage in the first trimester.

• Carbonell et al (1997b) demonstrated that for gestations less than 63 days, misoprostol, given in a dose of 800 mcg vaginally and repeated at 48 and 96 hours, resulted in a 92 percent complete abortion rate, with 77 percent complete after one dose and an additional 13.7 percent after the second dose; there was a failure rate of 8 percent. Hausknecht (1995), Creinin et al (1995) and Carbonell et al (1997a) all reported a 90–96 percent complete abortion rate with methotrexate followed by misoprostol at 3, 5 and 7 days in a dose of 800 mcg; 20 percent of patients required two or three doses.

• In a review of the literature, Grimes (1997) concluded that class I evidence and class A recommendations for first trimester abortion existed for misoprostol as the most effective prostaglandin, either as a single agent or as an adjunct (most effective at the seventh day) to mifepristone or methotrexate.

• El Refaey et al (1995) compared oral and vaginal doses and found vaginal misoprostol use resulted in fewer failures.

These studies clearly establish misoprostol as an effective agent to "empty" the pregnant uterus in the first trimester. One could assume similar effectiveness when it is given for a "failed" pregnancy or missed abortion. Blood loss in all of these studies was acceptable and comparable to blood loss during surgical abortion.

Misoprostol is associated with birth defects in "continuing pregnancies," and this is an obvious concern with unsupervised use.

Source: Gonzalez et al 1998; Hofmeyr et al 1998; Pastuszak et al 1998. 

This association is confirmed by several studies in Brazil, where misoprostol is readily available over the counter. Moebius syndrome, characterized by equinovarus, cranial nerve defects, arthrogryposis and terminal limb defects, has been described with exposure to a failed single dose of 800 mcg. Localized ischemia in the placental bed and vascular disruption in the embryo are postulated as the operational mechanism for causing the congenital anomalies.

Misoprostol Use in Incomplete Abortion

Table 1. Misoprostol for Incomplete Abortion

Source: Chung et al 1997.

The only prospective randomized study in the literature (Herabutya and O-Prasertsawat 1997) compared 200 mcg of misoprostol and placebo over a 24-hour period prior to suction curettage (see below).

Source: Herabutya and O-Prasertsawat 1997.

Thirty out of 42 patients (71 percent) in the misoprostol group had a spontaneous abortion, versus six out of 42 in the placebo group. All complications were in the placebo group (bleeding and perforation in three), none in the misoprostol group. No systemic evaluation of blood loss or hematocrit changes was undertaken.

In the Chung et al (1995, 1997) and Herabutya and O-Prasertsawat (1997) studies, the diagnosis of incomplete abortion was made by transvaginal ultrasound. In the second Chung et al study, about one third of the patients with a clinical diagnosis of incomplete abortion had an empty uterus and did not need any treatment.

Chipcase and James (1997) demonstrated in a randomized trial of expectant management of surgical versus expectant management of spontaneous abortion that with less than 50 mm tissue present on ultrasound, curettage is probably not necessary. None of these studies found an increased risk of infection with the use of misoprostol. Indirect evidence from an analysis of postabortion complications in Brazil found a lower incidence of infections after self-administered misoprostol use than after other means of inducing abortion.

Source: Faundes et al 1996.