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Does the route of misoprostol matter?

Answers for healthcare providers on routes of misoprostol administration and what they mean for medication abortion care.

by Nicole Cieri-Hutcherson, PharmD, BCPS, NCMP

published 12/17/24

Misoprostol is a prostaglandin E1 analog that binds to smooth muscle cells in the uterus, causing contractions. Although approved for oral administration in preventing and treating gastrointestinal damage caused by NSAID use, misoprostol has several gynecologic off-label uses. These off-label uses of misoprostol include medication abortion, medication management of early pregnancy loss, induction of labor, cervical preparation before gynecologic procedures including IUD placement, and the treatment of postpartum hemorrhage.

How is misoprostol used for medication abortion?

The most effective medication abortion regimens include mifepristone and misoprostol, taken together as a two-drug regimen. It’s also the FDA-approved option for medication abortion. In early pregnancy. Adding mifepristone, a progesterone antagonist, before misoprostol increases medication abortion efficacy by blocking progesterone, which is needed to maintain a pregnancy. The efficacy rate of mifepristone and misoprostol for medication abortion ranges from 91.6% -is 99.7% depending on the gestational duration and the exact regimen used. Other options for medication abortion, like using misoprostol alone, are still safe and highly effective, even if they aren’t as effective as medication abortion with mifepristone and misoprostol. After medication abortion, regardless of regimen, patients should confirm that the regimen was effective and they are no longer pregnant.

How is misoprostol typically administered?

For medication abortion, the FDA-approved regimen is: day one, mifepristone 200 mg taken orally. Then, 24 to 48 hours after taking mifepristone, 800 mcg of misoprostol taken buccally (in the cheek pouch). Other evidence-based regimens include recommending shorter (or longer) intervals between mifepristone and misoprostol, alternative administration methods, such as vaginally or sublingually, additional doses of misoprostol, and use for gestational durations beyond the FDA-approved 70 days. Safe and effective regimens for medication management of early pregnancy loss (EPL) are identical to those used for medication abortion.

What are other ways misoprostol could be administered?

Other than buccally, misoprostol has been studied when administered sublingually, vaginally, and orally for abortion.

A pharmacokinetic study suggests that buccal and oral administration of misoprostol have the fastest onset of action compared to vaginal administration. Detectable concentrations appear to last longer with vaginal administration of misoprostol.

The clinical efficacy of oral misoprostol appears to decrease with increasing gestational duration. Although a high drug concentration is reached quickly with oral misoprostol, these levels drop too low before adequate clinical effect on the uterus. This research shows that a single oral dose of 400 mcg of misoprostol following mifepristone appears to be effective up to seven weeks gestation.

Other clinical studies have found that vaginal administration of misoprostol, drug levels are maintained at a low level for a longer period of time, which means avoiding the rapid decline in levels seen with oral misoprostol. Lower levels may also mean fewer side effects. A vaginal dose of 800 mcg misoprostol following mifepristone appears to be effective up to nine weeks’ gestation. Beyond nine weeks' gestation, additional doses of misoprostol can increase the efficacy of medication abortion.

Sublingual misoprostol has most recently been studied and appears to be an effective alternative to buccal. Preliminary studies suggest that a complete abortion rate with 600 to 800 mcg of sublingual misoprostol following mifepristone is comparable to vaginal misoprostol.

What about misoprostol-only regimens?

Medication abortion regimens with mifepristone and misoprostol are safe and effective; however, mifepristone may be contraindicated, unavailable, or inaccessible. The good news is misoprostol-only regimens for medication abortion up to 12 weeks are safe and effective. When misoprostol is used alone, 800 mcg of misoprostol is taken sublingually or vaginally every three hours for three to four doses total. Repeated doses are needed to maintain a reasonably high level and increase the efficacy. Unfortunately, this higher dose results in a higher risk of side effects such as diarrhea, fever, and chills.

Bottom line

Medication abortion with mifepristone and misoprostol as part of a two-drug regimen or a misoprostol-only regimen for medication abortion is safe and highly effective. Pharmacokinetic and clinical studies support administering misoprostol buccally, and other data support oral, vaginal, and sublingual misoprostol administration for medication abortion.

Nicole Cieri-Hutcherson (she/her) is a clinical pharmacist specializing in internal medicine and reproductive health. She practices in acute care at Buffalo General Medical Center and is a clinical assistant professor at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences in Buffalo, NY. Her passion is reproductive health, specifically contraceptive care, menopause management, and drug selection during pregnancy and lactation. At home, she’s mom to 4 beautiful kiddos and enjoys photography and baking.
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