Introduction
Misoprostol is a synthetic prostaglandin E1 analog that plays a significant role in obstetric, gynecologic, and gastrointestinal medicine. Originally developed for preventing NSAID-induced gastric ulcers, its uterotonic properties have made it invaluable in reproductive healthcare. This versatile medication requires careful clinical consideration due to its potent effects and potential complications.
Mechanism of Action
Misoprostol exerts its effects through prostaglandin receptor activation. In gastrointestinal applications, it inhibits gastric acid secretion and stimulates bicarbonate and mucus production, providing cytoprotective effects. In obstetric applications, it causes cervical ripening through collagen breakdown and stimulates uterine contractions by increasing intracellular calcium in myometrial cells. The drug also exhibits oxytocic properties that promote uterine emptying.
Indications
FDA-approved indications:- Prevention of NSAID-induced gastric ulcers in high-risk patients
- Medical management of first-trimester miscarriage
- Cervical ripening prior to surgical procedures
- Labor induction
- Treatment of postpartum hemorrhage
- Medical abortion (typically in combination with mifepristone)
Dosage and Administration
Gastric ulcer prevention: 200 mcg orally four times daily with food Obstetric uses:- Cervical ripening: 25-50 mcg vaginally or buccally every 3-6 hours
- Labor induction: 25-50 mcg vaginally every 4-6 hours
- Postpartum hemorrhage: 600-1000 mcg rectally or sublingually
- Medical abortion: 800 mcg buccally or vaginally following mifepristone
- Renal impairment: Use with caution; consider dose reduction
- Hepatic impairment: No specific recommendations; use cautiously
- Elderly: Lower doses may be appropriate due to increased sensitivity
Pharmacokinetics
Absorption: Rapidly absorbed through oral, vaginal, buccal, and sublingual routes. Bioavailability varies by route: oral (~80%), vaginal (~30% but more sustained), buccal/sublingual (~60-70%). Distribution: Highly protein-bound (~85%). Crosses placenta and blood-brain barrier. Metabolism: Rapidly de-esterified to misoprostol acid (active metabolite) in plasma and tissues. Elimination: Primarily renal excretion (80%), with terminal half-life of 20-40 minutes for misoprostol acid.Contraindications
- Pregnancy (when used for GI indications)
- Known hypersensitivity to prostaglandins
- History of cesarean delivery or uterine surgery (relative contraindication for obstetric use)
- Undiagnosed vaginal bleeding
- Active cardiovascular disease
Warnings and Precautions
Black Box Warning: Use during pregnancy can cause abortion, premature birth, or birth defects. Uterine rupture has been reported with obstetric use, particularly in women with prior uterine surgery. Additional precautions:- Use with extreme caution in patients with renal impairment
- May cause significant diarrhea and abdominal cramping
- Risk of incomplete abortion requiring surgical intervention
- Potential for hyperstimulation during labor induction
- Cardiovascular events reported in susceptible patients
Drug Interactions
- Magnesium-containing antacids: May increase diarrhea
- Oxytocin: Potentiates uterotonic effects; avoid concurrent use
- NSAIDs: Misoprostol may reduce their ulcerogenic effects
- Corticosteroids: May diminish misoprostol's gastrointestinal protective effects
Adverse Effects
Common (>10%):- Diarrhea (dose-dependent)
- Abdominal pain/cramping
- Nausea
- Flatulence
- Headache
- Uterine rupture
- Incomplete abortion
- Fetal bradycardia
- Anaphylaxis
- Uterine hyperstimulation
- Postpartum hemorrhage
Monitoring Parameters
- For GI use: Renal function, symptoms of diarrhea/dehydration
- For obstetric use:
- Uterine activity and fetal heart rate patterns - Vital signs, especially temperature (may cause pyrexia) - Blood loss assessment - Cervical changes - Signs of hyperstimulation
- Laboratory monitoring: Hemoglobin/hematocrit with significant bleeding
Patient Education
- Take with food to reduce gastrointestinal side effects
- Expect possible diarrhea, abdominal cramping, and spotting
- Use effective contraception while taking for GI indications
- Immediately report fever, severe abdominal pain, or heavy bleeding
- Understand risks and benefits when used for obstetric indications
- Do not share medication with others
- Follow specific instructions for route of administration (oral vs. vaginal vs. buccal)
References
1. American College of Obstetricians and Gynecologists. (2020). Practice Bulletin No. 225: Management of Stillbirth. Obstetrics & Gynecology, 136(2), e61-e88. 2. Drugs.com. (2023). Misoprostol Professional Monograph. 3. FDA Prescribing Information. (2022). Cytotec (misoprostol) tablets. 4. World Health Organization. (2018). Medical management of abortion. 5. Tang, O. S., & Gemzell-Danielsson, K. (2020). Misoprostol: Pharmacokinetics and therapeutic applications. International Journal of Women's Health, 12, 567-580. 6. Goldberg, A. B., & Drey, E. A. (2021). Misoprostol in obstetrics and gynecology. Current Opinion in Obstetrics and Gynecology, 33(6), 439-444.
Note: This information is intended for educational purposes only and should not replace professional medical advice. Always consult healthcare providers for personalized medical guidance.