The Medical Letter ®

on Drugs and Therapeutics

Volume 65 June 26, 2023

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In Brief: Alternatives to Mifepristone for Medication Abortion .........................................p 102

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The Medical Letter ®

on Drugs and Therapeutics

Volume 65 (Issue 1679) June 26, 2023

Take CME Exams

IN BRIEF
Table 1. Dosage and Cost of Mifepristone and Misoprostol
Alternatives to Mifepristone for Drug Usual Dosage1 Cost2
Medication Abortion Mifepristone3 – generic
Mifeprex (Danco)
200 mg PO once4 $67.00
43.00
The possibility that use of mifepristone (Mifeprex, Misoprostol5 – generic With Mifepristone: 5.00
Cytotec (Pfizer) 800 mcg buccally 24-48 hrs 23.20
and generics) may be restricted has led to questions after mifepristone
about alternatives for medication abortion. Alone:
800 mcg buccally,
MIFEPRISTONE PLUS MISOPROSTOL ― The sublingually, or intravaginally6
q3 hrs x 3-4 doses7
antiprogestin mifepristone is FDA-approved 1. For first-trimester medication abortion.
for termination of intrauterine pregnancy of up 2. Approximate WAC for one 200-mg tablet of mifepristone or four
200-mcg tablets of misoprostol. WAC = wholesaler acquisition cost
to 70 days’ gestation in a regimen with the E1 or manufacturer’s published price to wholesalers; WAC represents
prostaglandin analog misoprostol (Cytotec, and a published catalogue or list price and may not represent an actual
transactional price. Source: AnalySource® Monthly. June 5, 2023.
generics). The regimen, which consists of a single Reprinted with permission by First Databank, Inc. All rights reserved.
©2023. www.fdbhealth.com/policies/drug-pricing-policy.
oral 200-mg dose of mifepristone followed 24 to 48 3. FDA-approved, in a regimen with misoprostol, for medical termination of
hours later by buccal administration of 800 mcg of intrauterine pregnancy through 70 days’ gestation. Available as 200-mg
tablets.
misoprostol, has had a success rate (expulsion of 4. Followed by administration of misoprostol 24-48 hours later.
5. Available as 100- or 200-mcg tablets. Not FDA-approved for use alone
the gestational sac without surgical intervention) of for medical termination of pregnancy.
97% in pregnancies of up to 70 days’ gestation.1 6. Moistening the tablets before insertion may improve efficacy.
7. EG Raymond et al. Contraception 2023; 121:109998.

MISOPROSTOL ALONE ― In a meta-analysis of 38

studies in 12,829 women with viable pregnancies in a regimen consisting of a single intramuscular
the first trimester, treatment with various routes of injection of methotrexate (50 mg/m2), followed 5 to
administration and dosages of misoprostol alone 7 days later by misoprostol 800 mcg intravaginally
induced a complete abortion in 78% of women. In (a second dose of misoprostol could be given if
a subgroup analysis of 20 studies in 5338 women termination did not occur after 7 days), resulted
who received ≥3 doses of misoprostol (with a in a successful medical abortion in 171 women
first dose of 800 mcg buccally, sublingually, or (96%); a second dose of misoprostol was required
intravaginally), a complete abortion occurred in in 25 women (14%).3 In an uncontrolled trial of oral
87%. If misoprostol is used intravaginally, moisten- methotrexate 50 mg plus intravaginal misoprostol
ing the tablets before insertion has been reported 800 mcg, 233 of 299 women (78%) with pregnancies
to improve effectiveness.2 of up to 49 days’ gestation had complete abortions
within 8 days of taking methotrexate.4 No serious
Common adverse effects of misoprostol include
adverse events or complications were reported in
uterine cramping, nausea, and vomiting. Fever, chills,
either trial.3,4
and diarrhea are also common and may occur more
frequently when taken without mifepristone. The Methotrexate can cause anorexia, nausea, vomiting,
rate of hospitalization or transfusion reported in the abdominal cramps, fatigue, stomatitis, and amino-
meta-analysis was <1%.2 transferase elevations.

METHOTREXATE PLUS MISOPROSTOL ― LETROZOLE PLUS MISOPROSTOL ― The aromatase

Methotrexate is toxic to trophoblastic tissue inhibitor letrozole inhibits production of estrogen,
and has been used to treat unruptured ectopic which has a critical role in early pregnancy.
pregnancies. In an uncontrolled trial in 178 women Randomized trials in which letrozole was given for
with a pregnancy duration of ≤63 days’ gestation, 3-7 days before misoprostol for termination of early

102
Published by The Medical Letter, Inc. • A Nonprofit Organization • medicalletter.org
 The Medical Letter ®
Vol. 65 (1679) June 26, 2023

pregnancy have produced mixed results with some

showing an increased rate of completed abortions 1. MJ Chen and MD Creinin. Mifepristone with buccal
misoprostol for medical abortion: a systematic review.
with the addition of letrozole to misoprostol and Obstet Gynecol 2015; 126:12.
others showing no increase. Addition of letrozole to 2. EG Raymond et al. Medication abortion with misoprostol-
misoprostol was not associated with an increase in only: a sample protocol. Contraception 2023; 121:109998.
3. R Hausknecht. Methotrexate and misoprostol to terminate
adverse events or complications.5,6
early pregnancy. N Engl J Med 1995; 333:537.
4. MD Creinin et al. Medical abortion with oral methotrexate
Letrozole can cause hot flashes, fatigue, dizziness,
and vaginal misoprostol. Obstet Gynecol 1997; 90:611.
nausea, and musculoskeletal adverse effects. 5. CM Nash et al. Letrozole pretreatment prior to medical
termination of pregnancy: a systematic review.
CONCLUSION ― Use of buccal, sublingual, or Contraception 2018; 97:504.
intravaginal misoprostol alone is well established 6. Y Zhuo et al. The efficacy of letrozole supplementation for
as a safe and effective method for first-trimester medical abortion: a meta-analysis of randomized controlled
trials. J Matern Fetal Neonatal Med 2021; 34:1501.
abortion. If mifepristone becomes unavailable for
medication abortion, misoprostol alone appears to
be the best alternative. ■

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