Misoprostol

• NSAID-Induced Ulcer Prevention
• Labor Induction
• Postpartum Hemorrhage
• Miscarriage Management

Misoprostol is a synthetic prostaglandin E1 analog with multiple clinical applications, including prevention of NSAID-induced gastric ulcers, cervical ripening, labor induction, and treatment of postpartum hemorrhage. Its versatility stems from its effects on both the gastrointestinal tract and uterine smooth muscle.

Mechanism of Action

Gastrointestinal Effects:

• Replaces the cytoprotective prostaglandins depleted by NSAIDs
• Stimulates mucus and bicarbonate secretion
• Enhances mucosal blood flow
• Inhibits gastric acid secretion

Uterine Effects:

• Binds to myometrial EP2 and EP3 receptors
• Causes cervical softening (ripening) and dilation
• Stimulates uterine contractions
• Increases uterine tone

Available Formulations

Misoprostol is available as:

• Oral tablets: 100 mcg, 200 mcg

Tablets may be administered:

• Orally
• Sublingually (under the tongue)
• Buccally (between cheek and gum)
• Vaginally
• Rectally

Different routes have different pharmacokinetics and are selected based on indication.

Medical Uses

FDA-Approved Indication:

• Prevention of NSAID-induced gastric ulcers in high-risk patients

Off-Label Uses (Evidence-Based, Common):

• Cervical ripening before surgical procedures
• Labor induction
• Treatment of postpartum hemorrhage
• Medical management of miscarriage
• In combination with mifepristone for medication abortion

Dosing Guidelines

NSAID-Induced Ulcer Prevention:

• 200 mcg four times daily with food
• If not tolerated, 100 mcg may be used
• Take for duration of NSAID therapy

Labor Induction (off-label):

• Vaginal: 25 mcg every 3-6 hours
• Oral: 25-50 mcg every 4 hours
• Lower doses for patients with prior cesarean (if used at all - controversial)

Postpartum Hemorrhage (off-label):

• Sublingual: 800 mcg as a single dose
• Rectal: 800-1000 mcg as a single dose

Incomplete/Missed Miscarriage (off-label):

• Vaginal: 800 mcg as a single dose
• May repeat in 3-7 days if needed

Important Safety Information

Black Box Warning:

• Can cause abortion, premature birth, or birth defects
• Not for use in pregnant women unless used for specific reproductive indications
• Women must use effective contraception while taking for GI indications

Contraindications:

• Known allergy to prostaglandins
• Pregnancy (for GI indications)

Warnings and Precautions:

• Uterine rupture risk (especially with prior cesarean or uterine surgery)
• Should be used in obstetric settings with fetal monitoring when used for labor
• GI side effects (diarrhea) are dose-related

Drug Interactions

• Magnesium-containing antacids: May worsen diarrhea
• Oxytocin: Concurrent use increases uterine rupture risk
• NSAIDs: Therapeutic combination for GI protection but does not prevent NSAID-induced renal effects

Special Populations

• Pregnancy:
  • Contraindicated for GI indications (teratogenic)
  • Used specifically for reproductive indications under medical supervision
• Lactation: Not recommended; excreted in breast milk
• Renal Impairment: No specific adjustment but use with caution
• Elderly: May have increased sensitivity; consider lower doses

Obstetric Safety Considerations

When used for labor induction:

• Have tocolytics available
• Continuous fetal heart rate monitoring required
• Avoid in patients with prior uterine surgery (relative contraindication)
• Avoid hyperstimulation (more than 5 contractions in 10 minutes)