Misoprostol alone

Overview and history

Despite evidence demonstrating the safety and efficacy of the mifepristone/misoprostol regimen, political and commercial difficulties present challenges to widespread production and distribution of mifepristone. Beginning in the early 1990s, researchers revisited the possibility of using misoprostol alone as a method of terminating early pregnancies. A growing body of evidence has now shown that misoprostol can be used as a single agent to induce early abortion [1]

Misoprostol is widely prescribed for the prevention and treatment of gastric ulcers and has been approved for this indication in nearly 100 countries worldwide. In a number of countries, misoprostol is also specifically approved for obstetric and gynecologic uses. Misoprostol is inexpensive, stable at ambient temperatures, easy to transport, easy to administer, and does not require refrigeration, even in hot climates. Thus misoprostol has potential to significantly expand medication abortion access in developing countries. Research on the optimal dosing and administration strategy is ongoing.

Misoprostol-only experience worldwide

Many women, particularly in countries with restrictive abortion laws, attempt to terminate early pregnancies with misoprostol alone [2]. Reports from Latin America suggest that women frequently use misoprostol to induce abortion early in pregnancy. However, without standardized information and instructions, women utilize misoprostol in a numerous ways, with a high degree of variation in both dosage and timing [3].Some of these regimens are not as effective as others and thus providing both health service providers and individual women with information about the evidence-based regimen for misoprostol use is critical.

As indicated on the map below, misoprostol is currently registered in nearly 100 countries worldwide. In most countries, misoprostol has been approved specifically for use in the prevention and treatment of gastric ulcers but is often used "off label" for its many obstetric and gynecological indications. In an increasing number of countries, misoprostol has been approved specifically for Ob/Gyn indications, including post-partum hemorrhage prevention, incomplete abortion management, and, in conjunction with mifepristone, early pregnancy termination.

Due to its use as an abortifacient, some governments have attempted to restrict access to and use of misoprostol. Thus, the availability and cost of misoprostol may vary widely, even in countries that have approved misoprostol for one or more indications. Misoprostol may be available in countries in which it has not been formally "approved," typically through the black market or from retail pharmacists. The misoprostol available through unregulated markets may be of variable quality and cost.

Because misoprostol is widely available, generally inexpensive, and stable at room temperature, misoprostol is a suitable abortifacient in resource poor settings, particularly when other safe abortion options (such as mifepristone/misoprostol) are not available.

Misoprostol-only experience in the US

In the US, misoprostol (brand name Cytotec®) has been approved by the Food and Drug Administration (FDA) only for the prevention and treatment of gastric ulcers. However, clinicians routinely use misoprostol off-label for obstetric and gynecological purposes, including cervical ripening, labor induction, and mid-trimester terminations [4]. Further, the FDA has approved the use of misoprostol in conjunction with mifepristone for the termination of early pregnancies.

Misoprostol-only regimens are not widely used in the US, where mifepristone and misoprostol, methotrexate and misoprostol, and aspiration abortion services are available. However, the off-label use of misoprostol as a single agent abortifacient has been documented, particularly among Latinas in the US [5].

Mechanism of action of misoprostol

Prostaglandins are naturally occurring fatty acids produced by many tissues in the body. Prostaglandin E₁ causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a cascade of events, including a change in calcium concentration, thereby initiating muscle contraction.

Misoprostol is an analog of prostaglandin E₁. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents. Misoprostol is relatively metabolically resistant and thus has prolonged action [6].

Misoprostol-only protocol

Determining the optimal protocol for the use of misoprostol as a single agent abortifacient has been an active area of investigation. Researchers throughout Latin America and East Asia have explored vaginal and sublingual regimens, a variety of doses, and different dosing schedules. Overall, these studies have shown that misoprostol alone can be effectively used in different clinical environments at a variety of gestational ages.

The results of these studies have informed the development of a consensus regimen for the use of misoprostol for the termination of an early pregnancy. The optimal regimen for pregnancies through nine weeks is the vaginal administration of 800µg (micrograms) of misoprostol followed 24 hours later with the vaginal administration of a second 800µg dose of misoprostol (2 x 800µg) . Instructions for the use of misoprostol for early abortion can be found in the educational materials and resources section of this website.

Misoprostol is absorbed through mucosal surfaces. Research is ongoing to determine if buccal administration (placing the medication between the cheek and the gum) and/or sublingual administration (placing the medication under the tongue) are as or more effective in inducing an early abortion than vaginal administration. Indeed, there is some evidence that suggests that the vascularity of the buccal area would allow for more rapid absorption. Studies investigating both buccal and sublingual administration appear promising. However, the current best-evidence supports vaginal administration of misoprostol over other routes of administration.

Efficacy

A review of the available research indicates that the efficacy of misoprostol as a sole abortifacient varies by route of administration, dose, dosing schedule, and gestational age. Unfortunately, most of the studies had small samples, took place at a range of gestational ages, tested different variations in the regimen, and showed a range of results (with completion rates of 65% to 93%).

However, the best available evidence suggests that the optimal protocol (800µg of misoprostol administered vaginally followed 24 hours later with the vaginal administration of a second 800µg dose) has an overall completion rate of 75% to 85% when used in the first nine weeks of pregnancy. [7]There is evidence that the efficacy of this regimen can be enhanced if the misoprostol tablets are moistened with a few drops of clean water prior to vaginal insertion.

In the roughly 15%-25% of cases where misoprostol administration does not lead to a complete abortion, additional intervention in required. Recent studies have shown that approximately 10% of women using misoprostol for early pregnancy termination will experience an ongoing pregnancy. A woman may take an additional 800µg dose of misoprostol or she may need an aspiration intervention. Reasons for aspiration intervention include prolonged or excessive bleeding, incomplete abortion (remnants of fetal tissue in the uterus), or an ongoing pregnancy.  An aspiration termination may also be performed at the request of the woman or the provider.

The misoprostol-only regimen has the potential to expand access to safe abortion services in resource poor and developing country settings. However, the misoprostol-only regimen is not as effective as either the mifepristone/misoprostol or the methotrexate/misoprostol regimen. Further, the side effects associated with the misoprostol-only regimen, while tolerable, are generally more severe than those associated with the combined regimens.

Eligibility

Most women early in their pregnancies appear to be eligible for the misoprostol-only regimen. If the use of misoprostol-only results in an incomplete abortion or a continued pregnancy, vacuum aspiration or D&C may be necessary. Women considering the misoprostol-only regimen should we willing to undergo a vacuum aspiration procedure, if indicated.

Contraindications

Few contraindications to misoprostol use are described in the medical literature and most women with an intra-uterine pregnancy of nine weeks or less are eligible for misoprostol use. If a woman has a documented allergy to prostaglandins, in general, or misoprostol specifically, she should not use misoprostol. If an ectopic pregnancy is confirmed or strongly suspected, the woman should not use misoprostol. Finally, if a woman has an intrauterine device (IUD) in her uterus (an IUD in situ), the device should be removed before the administration of misoprostol.

Women with uterine infections, severe anemia, cardiovascular and cerebrovascular diseases, coagulopathy or current therapy with anticoagulants, and hypertension were excluded from some clinical studies. In these cases, use of misoprostol should be evaluated on a case by case basis. There is no evidence that misoprostol is harmful to breastfeeding infants. However, women may be advised to discard breast milk for 24 hours after the administration of misoprostol. In addition, women are advised not to engage in vaginal intercourse or insert anything into the vagina for approximately one week after misoprostol use.

Side Effects and Complications

Abdominal cramping and bleeding are hallmarks of the abortion process itself. Many women report that cramps and abdominal pain are similar to those associated with a heavy menstrual period. Vaginal bleeding can vary significantly in both duration and severity and many women report that the bleeding resembles a very heavy period or an early miscarriage. Bleeding can be heavier than a heavy period and last for weeks. The majority of studies conducted on the misoprostol-only regimen have reported that the mean duration of bleeding is approximately two weeks. Many women report passing blood clots, which can be large, and some women report passing gray or tan tissue (the products of conception). This tissue is usually less than one or two inches in length.

Reported side effects include nausea, vomiting, diarrhea, dizziness, headache, fever, chills, rashes, and pelvic pain. In most cases, these side effects are transient and resolve within 2-24 hours after misoprostol administration. Of women who report pelvic pain after using the misoprostol-only regimen, approximately 25% report that the pain was much stronger than menstrual pain. In most cases, side effects and pelvic pain can be managed with oral analgesics.

A number of case reports from Brazil have associated fetal exposure to misoprostol with an increased risk of limb and central nervous system abnormalities. However, the absolute risk associated with in utero misoprostol exposure appears low. Women electing to use the misoprostol-only regimen should be informed of the possible teratogenic effects of misoprostol that may occur if the medication fails to induce an abortion and if the pregnancy is then carried to term [8].

Complications

Few complications have been reported with the optimal misoprostol-only regimen. However, the woman should contact a provider if:

1) She experiences fever or chills beyond 24 hours after misoprostol administration;
2) She soaks more than two maxi pads (or thick towels) an hour for two consecutive hours or if she experiences continuous bleeding for several weeks;
3) She experiences an abrupt onset of heavy bleeding two weeks or more after having taken misoprostol; and/or
4) She has no or scant bleeding in the seven days after misoprostol administration.

In approximately 15%-20% of cases, the abortion is incomplete and either an additional dose of misoprostol or an aspiration intervention is required. As use of misoprostol leads to cervical dilation, mechanical dilation is generally unnecessary if an aspiration abortion is performed [9].

Acceptability

Few studies have directly assessed the acceptability of misoprostol-only regimens. Although side effects of greater severity are associated with the misoprostol-only regimen, the majority of patients report that the side effects are tolerable. Patient satisfaction with the vaginal regimen is high and the majority of patients state that they would use the misoprostol method for a future termination and would also recommend the method to others.

Additional Uses of Misoprostol

Misoprostol is used for a wide array of conditions including the treatment and prevention of gastric ulcers. Misoprostol is also used for a variety of obstetric and gynecological health indications, including the induction of labor, cervical ripening, and second trimester abortion. Misoprostol is also effective in both preventing and treating postpartum hemorrhage, managing early pregnancy loss (both incomplete and missed abortion), and in providing post-abortion care [10].

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Citations in this section
[1] Blanchard K, Winikoff B and Ellertson C,1999.
[2] Barbosa R and Arilha M, 1993.
[3] Costa S and Vessey M, 1993.
[4] Blanchard K et al, 2002.
[5] Rosing M and Archbald C, 2000.
[6] Baird D, 2000.
[7] Consensus Statement, 2003.
[8] Philip N, Shannon C and Winikoff B, 2003.
[9] Carbonell Esteve J et al, 1998.
[10] Creinin M, Schwartz J, Guido R and Pymay H, 2001.

For the full bibliographic citations of all references listed in this section, please visit our reference section.