What are the uses and precautions of Misoprostol (prostaglandin E1 analogue)?

Misoprostol: Clinical Uses and Essential Precautions

Primary Indications

Misoprostol is a synthetic prostaglandin E1 analogue with FDA approval for prevention and treatment of NSAID-induced gastric ulcers, but has become widely used off-label in obstetrics for labor induction, pregnancy termination, and cervical ripening. 1

FDA-Approved Use

• Prevention of NSAID-induced gastric ulcers at 800 mcg daily in divided doses, with healing rates of 60-80% for duodenal ulcers and comparable efficacy to H2-receptor antagonists 2, 3
• Misoprostol should be prescribed alongside NSAIDs for patients requiring gastroprotection, particularly those with history of NSAID-associated ulcers 4

Obstetric Applications (Off-Label)

Labor Induction:

• The optimal regimen is 20-25 mcg oral solution every 2-6 hours, which results in fewer cesarean sections and lower uterine hyperstimulation rates compared to higher doses 5
• Oral administration is superior to vaginal route, with 31% reduction in hyperstimulation (RR 0.69) and 16% reduction in cesarean sections compared to vaginal dinoprostone (RR 0.84) 5
• Continuous fetal heart rate and uterine activity monitoring is mandatory from 30 minutes to 2 hours after each dose 5

Pregnancy Termination:

• For second-trimester termination, 400 mcg vaginally every 3-6 hours is the optimal regimen when mifepristone is unavailable 6
• Doses exceeding 800 mcg increase side effects, particularly diarrhea, without improving efficacy 6
• In first trimester, dilatation and evacuation remains safest; prostaglandins are reserved for when surgery is not feasible 4

Critical Contraindications

Absolute Contraindications

Pregnancy (for ulcer prevention):

• Misoprostol is absolutely contraindicated in pregnant women being treated for NSAID-induced ulcers due to abortifacient properties 1
• Women of childbearing potential must have negative pregnancy test before initiation and use effective contraception throughout therapy 1

Previous Cesarean Delivery:

• Misoprostol is absolutely contraindicated for labor induction in women with prior cesarean section, with uterine rupture risk of 13% compared to 1.1% with oxytocin and 2% with prostaglandin E2 5, 7
• This contraindication extends to any prior uterine incision or surgery involving the uterus 7

Allergy:

• Contraindicated in patients with documented prostaglandin allergy 1

Essential Precautions

Cardiovascular Considerations

• Exercise caution in patients with pre-existing cardiovascular disease, as misoprostol can lower systemic vascular resistance and blood pressure while increasing heart rate 4, 1
• When used for pregnancy termination in cardiac patients, monitor systemic arterial oxygen saturation with pulse oximetry and consider norepinephrine infusion to support diastolic blood pressure 4

Hepatic Impairment

• In advanced liver failure, misoprostol may be less effective because it requires hepatic metabolism to convert from prostaglandin E1 to its active E2 form; consider alternative agents 5

Renal Disease

• While not specifically contraindicated, NSAIDs (which misoprostol protects against) should be avoided in renal disease, making the combination less relevant in this population 4

Common Adverse Effects

• Diarrhea occurs in approximately 10% of patients, typically mild and self-limiting 2, 3
• Minimize gastrointestinal effects by administering after meals and at bedtime 3
• Uterine hyperstimulation with fetal heart rate changes when used for labor induction, though less common with oral versus vaginal administration 5

Special Populations

Breastfeeding

• Limited data available; however, related NSAIDs (ibuprofen, indomethacin, naproxen) are safe during breastfeeding 4

Pediatric

• Not indicated for pediatric use; primary concern is accidental NSAID overdose prevention through proper storage 4

Clinical Advantages

• Significantly lower cost: $0.36-$1.20 per 100 mcg tablet versus $65-$75 for dinoprostone gel or $165 for dinoprostone insert 5
• Room temperature stability eliminates refrigeration requirements, unlike dinoprostone 5
• Multiple routes of administration (oral, vaginal, rectal, sublingual) provide flexibility 8

Critical Safety Monitoring

For Labor Induction:

• Continuous electronic fetal monitoring required 5
• Monitor for uterine hyperstimulation (more than 5 contractions in 10 minutes) 5
• Have tocolytics immediately available 5

For Ulcer Prevention:

• Patient must not share medication with others, particularly women of childbearing age 1
• Provide patient information leaflet with each prescription 1

Teratogenic Risk

• Failed abortion attempts carry teratogenic risk; thorough counseling about this risk is essential before prescribing for pregnancy termination 6, 9
• Teratogenic effects include limb defects and Möbius syndrome when pregnancy continues after misoprostol exposure 9