MISOPROSTOL
Clinical safety rating: avoid
No significant drug interactions Contraindicated in pregnancy due to abortifacient properties.
Misoprostol is a synthetic prostaglandin E1 analog that induces uterine contractions and cervical ripening by binding to prostaglandin receptors, leading to increased intracellular calcium and myometrial contraction. It also inhibits gastric acid secretion by reducing parietal cell activity and protecting gastric mucosa via increased bicarbonate and mucus production.
| Metabolism | Hepatic, primarily via de-esterification to misoprostol acid (active metabolite), which undergoes further oxidation and reduction; CYP450 minimal involvement; metabolites excreted renally. |
| Excretion | Primarily renal excretion of metabolites; ~80-90% of a radiolabeled dose is excreted in urine within 24 hours, with the remainder in feces. Misoprostol acid (active metabolite) undergoes further beta-oxidation and reduction; <1% excreted unchanged. |
| Half-life | 2-3 hours for misoprostol acid (active metabolite); clinically, a short duration requires multiple daily dosing. In patients with renal impairment, half-life may be prolonged but not significantly clinically. |
| Protein binding | 80-89% bound to albumin (specifically to human serum albumin). Binding is saturable at high concentrations. |
| Volume of Distribution | Apparent Vd of misoprostol acid: approximately 0.3-0.5 L/kg. This indicates distribution primarily into extracellular fluid; low tissue binding. |
| Bioavailability | Oral: ~60% (rapid and extensive first-pass metabolism to misoprostol acid); Vaginal/buccal/sublingual: bioavailability is higher (~70-80%) due to partial avoidance of first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes for antiulcer effect (gastric acid suppression); Vaginal: 20-30 minutes for cervical ripening; Buccal/sublingual: 10-15 minutes for uterine contractions. Onset is faster with sublingual/buccal administration. |
| Duration of Action | Oral: 3-6 hours for acid suppression; Vaginal: 5-6 hours for cervical ripening. Effect on uterine contractility lasts approximately 4-6 hours depending on dose and route. |
| Molecular Weight | 382.5 |
200 mcg orally four times daily (with meals and at bedtime) for prevention of NSAID-induced gastric ulcers; 800 mcg sublingually every 4 hours for up to 3 doses for labor induction; 25 mcg orally single dose for cervical ripening.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR > 30 mL/min; for GFR 10-30 mL/min, consider reducing oral dose by 50% if GI adverse effects occur; for GFR < 10 mL/min, use with caution and monitor for toxicity. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: No data, use with caution; Child-Pugh C: Not studied, avoid use. |
| Pediatric use | Safety and efficacy not established for most indications; for congenital heart disease with NSAID-induced ulcer risk, limited data suggest 2-5 mcg/kg/dose orally four times daily (max 200 mcg/dose). |
| Geriatric use | Start at lower end of dosing range (e.g., 100 mcg orally four times daily) due to increased risk of diarrhea and hypotension; titrate slowly based on tolerance. |
| 1st trimester | Category X: Miscarriage induction; teratogenic effects including Moebius sequence and limb defects reported. Avoid in pregnancy for cervical ripening/labor induction; use only for medical abortion or missed abortion. |
| 2nd trimester | Category X: Used off-label for cervical ripening and labor induction; contraindicated when uterine activity contraindicated. Increased risk of uterine hyperstimulation, rupture. |
| 3rd trimester | Category X: Used for cervical ripening, labor induction, postpartum hemorrhage. Contraindicated if prior cesarean or major uterine surgery due to rupture risk. |
Clinical note
No significant drug interactions Contraindicated in pregnancy due to abortifacient properties.
| FDA category | Contraindicated |
| Placental transfer | Actively crosses placenta; rapid and complete transfer of misoprostol acid observed in early pregnancy. Fetal levels similar to maternal. |
■ FDA Black Box Warning
Misoprostol is contraindicated in pregnant women for the prevention of NSAID-induced gastric ulcers because it can cause abortion. If used for induction of labor or abortion, careful patient selection and monitoring are required. It may cause uterine hyperstimulation, leading to fetal distress, uterine rupture, or maternal death.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to misoprostol or prostaglandinsPregnancy (when used for cervical ripening/labor induction) if contraindicated uterine activityUnexplained vaginal bleeding during pregnancyPrior cesarean section or major uterine surgery (for third-trimester cervical ripening/labor induction)Nonviable pregnancy with active labor (risk of uterine rupture)
| Precautions | Uterine hyperstimulation and rupture (especially with prior uterine surgery or grand multiparity), Fetal distress and meconium passage, Maternal hypotension and tachycardia, Gastrointestinal effects (diarrhea, abdominal pain), Avoid in pregnancy for peptic ulcer disease indication, Not to be used as a cervical ripener in patients with uterine scar or fetal distress |
Loading safety data…
| Breastfeeding | Excreted in breast milk in small amounts (misoprostol acid); not detected in infant plasma after maternal oral or vaginal doses. Considered compatible with breastfeeding by American Academy of Pediatrics. Use with caution in postpartum hemorrhage; no adverse effects reported in breastfed infants. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Misoprostol is a prostaglandin E1 analogue that stimulates uterine contractions and causes cervical ripening. It is contraindicated in pregnancy due to its abortifacient properties. First trimester exposure may cause uterine rupture, fetal death, or congenital anomalies (e.g., Möbius syndrome, limb defects). Second and third trimester use is limited to induction of labor or abortion; risks include uterine hyperstimulation, fetal distress, and meconium passage. Post-term effects: none specified. |
| Fetal Monitoring | Monitor maternal vital signs, uterine activity (contraction frequency, duration, and resting tone), and fetal heart rate continuously during labor induction. Assess for uterine hyperstimulation, tetanic contractions, or rupture. Monitor for adverse effects (nausea, vomiting, diarrhea, fever). In abortion protocols, monitor bleeding and completeness of evacuation. |
| Fertility Effects | No known adverse effects on fertility. Misoprostol does not impair female or male reproductive function in animal studies or human data. It is used off-label for cervical ripening prior to intrauterine procedures, which may temporarily affect implantation. |
| Food/Dietary | No specific food interactions. Avoid magnesium-containing antacids as they may worsen diarrhea. Take with food to reduce gastrointestinal upset. |
| Clinical Pearls | Misoprostol is a synthetic prostaglandin E1 analog used off-label for cervical ripening and labor induction, and for medical abortion in combination with mifepristone. It is also used for prevention of NSAID-induced gastric ulcers. For obstetric indications, it can be administered orally, sublingually, vaginally, or buccally, with dosing and route varying by protocol. Onset of action for cervical ripening is 6-8 hours. Contraindicated in pregnancy for ulcer prophylaxis due to abortifacient properties; must be used with caution in women of childbearing age. Common side effects include diarrhea, abdominal pain, and nausea. Misoprostol should not be given simultaneously with magnesium-containing antacids as they may worsen diarrhea. |
| Patient Advice | Take misoprostol exactly as prescribed; do not increase dose or frequency. · For ulcer prevention: take with food and at bedtime, and avoid taking with antacids containing magnesium. · If you are pregnant or could become pregnant, do not use misoprostol for ulcer prevention; it may cause miscarriage or birth defects. · Report severe diarrhea, abdominal pain, or vaginal bleeding to your healthcare provider. · For abortion or labor induction: discuss the full treatment plan and expected symptoms with your doctor. · Do not share this medication with others. |