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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(mye soe PROST ole)
Generic Available (U.S.)
Yes
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Prevention of NSAID-induced gastric ulcers; medical termination of pregnancy of ≤49 days (in conjunction with mifepristone)
Use: Unlabeled/Investigational
Cervical ripening and labor induction (except in women with prior cesarean delivery or major uterine surgery); fat malabsorption in cystic fibrosis
Pregnancy Risk Factor
X
Pregnancy Considerations
Teratogenic effects were not observed in animal reproduction studies; however, congenital anomalies following first trimester exposure, fetal death, uterine perforation, and abortion have been reported after the use of misoprostol in human pregnancy. [U.S. Boxed Warning]: Not to be used to reduce NSAID-induced ulcers in women of childbearing potential unless woman is capable of complying with effective contraceptive measures. Do not use in women of childbearing potential without a negative serum pregnancy test within 2 weeks prior to therapy; therapy is normally begun on the second or third day of next normal menstrual period. Use to prevent NSAID-induced ulcers is contraindicated in pregnant women. Written and verbal warnings concerning the hazards of misoprostol should be provided. During pregnancy, misoprostol may induce or augment uterine contractions; the manufacturer states that misoprostol should not be used as a cervical-ripening agent for induction of labor. However, The American College of Obstetricians and Gynecologists (ACOG) supports this off-label use in women who have not had a prior cesarean delivery or major uterine surgery. Hyperstimulation of the uterus, uterine rupture, or adverse events in the fetus or mother may occur with this use. Misoprostol is FDA approved for the medical termination of pregnancy of ≤49 days in conjunction with mifepristone.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Misoprostol acid (the active metabolite of misoprostol) has been detected in breast milk. Concentrations following a single oral dose were 7.6-20.9 pg/mL after 1 hour and decreased to <1 pg/mL by 5 hours. Adverse events have not been reported in nursing infants.
Contraindications
Hypersensitivity to prostaglandins; pregnancy (when used to reduce NSAID-induced ulcers)
Warnings/Precautions
Boxed warnings:
• Appropriate use: See “Other warnings/precautions” below
• Women of childbearing potential: See “Special populations” below.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Elderly: Use with caution in the elderly.
• Pregnancy: Uterine perforation and/or rupture have been reported in association with intravaginal use to induce labor or with combined oral/intravaginal use to induce abortion. The manufacturer states that Cytotec® should not be used as a cervical-ripening agent for induction of labor. However, The American College of Obstetricians and Gynecologists (ACOG) continues to support this off-label use.
• Women of childbearing potential: [U.S. Boxed Warning]: Not to be used to reduce NSAID-induced ulcers in women of childbearing potential unless woman is capable of complying with effective contraceptive measures; therapy is normally begun on the second or third day of next normal menstrual period.
Other warnings/precautions:
• Appropriate use: [U.S. Boxed Warning]: Due to the abortifacient property of this medication, patients must be warned not to give this drug to others.
Adverse Reactions
>10%: Gastrointestinal: Diarrhea, abdominal pain
1% to 10%:
Central nervous system: Headache
Gastrointestinal: Constipation, dyspepsia, flatulence, nausea, vomiting
<1%: Gynecological disorders (cramps, dysmenorrhea, hypermenorrhea, spotting, postmenopausal vaginal bleeding, and other menstrual disorders)
Postmarketing and/or case reports: Abnormal taste, abnormal vision, alkaline phosphatase increased, alopecia, anaphylaxis, anemia, amylase increase, anxiety, appetite changes, arrhythmia, arterial thrombosis, arthralgia, back pain, breast pain, bronchitis, bronchospasm, cardiac enzymes increased, chest pain, chills, confusion, conjunctivitis, CVA, deafness, depression, dermatitis, diaphoresis, dizziness, drowsiness, dysphagia, dyspnea, dysuria, earache, edema, epistaxis, ESR increased, fatigue, fetal or infant death (when used during pregnancy), fever, GI bleeding, GI inflammation, gingivitis, glycosuria, gout, hematuria, hepatobiliary function abnormal, hyper-/hypotension, impotence, loss of libido, MI, muscle cramps, myalgia, neuropathy, neurosis, nitrogen increased, pallor, phlebitis, pneumonia, polyuria, pulmonary embolism, purpura, rash, reflux, rigors, stiffness, syncope, thirst, thrombocytopenia, tinnitus, upper respiratory tract infection, urinary tract infection, uterine rupture, weakness, weight changes
Metabolism/Transport Effects
None known.
Drug Interactions
Antacids: May enhance the adverse/toxic effect of Misoprostol. More specifically, concomitant use with magnesium-containing antacids may increase the risk of diarrhea. Management: Avoid concomitant use of misoprostol and magnesium-containing antacids. In patients requiring antacid therapy, employ magnesium-free preparations. Monitor for increased adverse effects (e.g., diarrhea, dehydration). Exceptions: Aluminum Hydroxide; Calcium Carbonate; Sodium Bicarbonate. Risk D: Consider therapy modification
Carbetocin: Misoprostol may enhance the therapeutic effect of Carbetocin. Risk X: Avoid combination
Oxytocin: Misoprostol may enhance the therapeutic effect of Oxytocin. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Misoprostol peak serum concentrations may be decreased if taken with food (not clinically significant).
Storage
Store at or below 25°C (77°F).
Mechanism of Action
Misoprostol is a synthetic prostaglandin E1 analog that replaces the protective prostaglandins consumed with prostaglandin-inhibiting therapies (eg, NSAIDs); has been shown to induce uterine contractions
Pharmacodynamics/Kinetics
Absorption: Rapid and extensive
Metabolism: Hepatic; rapidly de-esterified to misoprostol acid (active)
Protein binding: Misoprostol acid: <90%
Half-life elimination: Misoprostol acid: 20-40 minutes
Time to peak, serum: Misoprostol acid: Fasting: 6-22 minutes
Excretion: Urine (80%)
Dosage
Oral:
Children 8-16 years: Fat absorption in cystic fibrosis (unlabeled use): 100 mcg 4 times/day
Adults:
Prevention of NSAID-induced gastric ulcers: 200 mcg 4 times/day with food; if not tolerated, may decrease dose to 100 mcg 4 times/day with food; last dose of the day should be taken at bedtime
Medical termination of pregnancy: Refer to Mifepristone monograph.
Intravaginal: Adults: Labor induction or cervical ripening (unlabeled uses): 25 mcg (1/4 of 100 mcg tablet); may repeat at intervals no more frequent than every 3-6 hours. Do not use in patients with previous cesarean delivery or prior major uterine surgery.
Dosage adjustment in renal impairment: Half-life, maximum plasma concentration, and bioavailability may be increased; however, a correlation has not been observed with degree of dysfunction. Decrease dose if recommended dose is not tolerated. It is not known if misoprostol is removed by dialysis
Administration: Oral
Incidence of diarrhea may be lessened by having patient take dose right after meals and avoiding magnesium-containing antacids. When used for the prevention of NSAID-induced ulcers, therapy is usually begun on the second or third day of the next normal menstrual period in women of childbearing potential.
Monitoring Parameters
Adequate diagnostic measures in all cases of undiagnosed abnormal vaginal bleeding
Dietary Considerations
Should be taken with food; incidence of diarrhea may be lessened by having patient take dose right after meals.
Patient Education
Take with meals or after meals to prevent nausea, diarrhea, and flatulence. You may experience increased menstrual pain or cramping. Report abnormal menstrual periods, spotting (may occur even in postmenstrual women), or severe menstrual bleeding.
Geriatric Considerations
Elderly, due to extensive use of NSAIDs and the high percentage of asymptomatic hemorrhage and perforation from NSAIDs, are at risk for NSAID-induced ulcers and may be candidates for misoprostol use. However, routine use for prophylaxis is not justified. Patients must be selected upon demonstration that they are at risk for NSAID-induced lesions. Misoprostol should not be used as a first-line therapy for gastric or duodenal ulcers.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Teach appropriate diet and lifestyle if being used to prevent ulcers.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 100 mcg, 200 mcg
Cytotec®: 100 mcg
Cytotec®: 200 mcg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Cytotec)
100 mcg (60): $100.99
200 mcg (60): $125.99
Tablets (Misoprostol)
100 mcg (60): $39.99
200 mcg (60): $57.01
References
American College of Obstetricians and Gynecologists, “ACOG Practice Bulletin No. 107: Induction of Labor,”Obstet Gynecol, 2009, 114(2, part 1):386-97.
American College of Obstetricians and Gynecologists Committee on Obstetric Practice, “ACOG Committee Opinion No. 342: Induction of Labor for Vaginal Birth After Cesarean Delivery,” Obstet Gynecol, 2006, 108(2):465-8.
Cleghorn GJ, Shepherd RW, and Holt TL, “The Use of a Synthetic Prostaglandin E1 Analogue (Misoprostol) as an Adjunct to Pancreatic Enzyme Replacement in Cystic Fibrosis,” Scand J Gastroenterol Suppl, 1988, 143:142-7.
Robinson PJ, Smith AL, and Sly PD, “Duodenal pH in Cystic Fibrosis and Its Relationship to Fat Malabsorption,” Dig Dis Sci, 1990, 35(10):1299-304.
Walt RP, “Misoprostol for the Treatment of Peptic Ulcer and Anti-inflammatory Drug-Induced Gastroduodenal Ulceration,” N Engl J Med, 1992, 327(22):1575-80.
Wing, DA, “Labor Induction With Misoprostol,” Am J Obstet Gynecol, 1999, 181(2):339-45.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
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