Misocon

Approved Indications:

• Prevention of NSAID-induced gastric ulcers in patients at high risk of complications from NSAID therapy (e.g., elderly, history of ulcer).
• Medical termination of intrauterine pregnancy in combination with mifepristone (FDA-approved regimen).
• Cervical ripening and labor induction in obstetric use (approved in many countries; off-label in some regions like the U.S.).
• Treatment of postpartum hemorrhage (PPH) due to uterine atony (approved or guideline-endorsed depending on region).

Clinically Accepted Off-label Uses:

• Management of missed or incomplete miscarriage (medically accepted and guideline-supported).
• Induction of abortion (monotherapy) where mifepristone is not available.
• Treatment of intrauterine fetal demise (IUFD).
• Cervical preparation prior to uterine surgical procedures, including dilation and curettage (D&C), hysteroscopy, or intrauterine device (IUD) insertion.
• Treatment of nonviable pregnancies or blighted ovum.

Adults:

1.        Prevention of NSAID-induced ulcers:

o    Dose: 200 mcg orally 4 times daily with meals and at bedtime.

o    Adjust to 100 mcg 4 times daily if not well tolerated.

2.        Medical abortion (with mifepristone):

o    Day 1: Mifepristone 200 mg orally.

o    24–48 hours later: Misoprostol 800 mcg buccally, sublingually, or vaginally as a single dose.

o    Repeat doses may be used per local protocols if expulsion is incomplete.

3.        Missed or incomplete abortion:

o    800 mcg vaginally or sublingually as a single dose; may repeat after 3–12 hours if necessary.

4.        Induction of labor (cervical ripening):

o    25 mcg vaginally or orally every 4–6 hours.

o    Maximum: 200 mcg total per 24 hours.

o    Avoid use if prior uterine surgery (e.g., C-section).

5.        Postpartum hemorrhage (PPH):

o    800–1000 mcg rectally as a single dose immediately after delivery if bleeding occurs due to uterine atony.

Geriatrics:

• For ulcer prevention, use adult dose; monitor for dehydration or diarrhea.

Pediatrics:

• Not routinely used in pediatric populations outside of adolescent reproductive care; dosing follows adult protocols in such cases.

Renal/Hepatic Impairment:

• Renal impairment: Use with caution; reduce dose if diarrhea occurs.
• Hepatic impairment: No dose adjustment routinely required, but monitor for tolerance.

Routes of Administration:

• Oral, vaginal, buccal, sublingual, or rectal depending on indication.

Duration:

• Ulcer prevention: Continued during NSAID therapy.
• Reproductive indications: Single-use or short-term protocol-based.

Misoprostol is a synthetic prostaglandin E1 (PGE1) analog. It binds to prostaglandin receptors on smooth muscle and epithelial cells. In the gastrointestinal tract, it inhibits gastric acid secretion by acting on parietal cells and enhances mucosal protective mechanisms by stimulating bicarbonate and mucus secretion. In the uterus, misoprostol stimulates uterine smooth muscle contraction by binding to myometrial prostaglandin receptors, resulting in cervical softening (ripening), uterine contractions, and expulsion of uterine contents. These effects explain its utility in ulcer prevention, medical abortion, labor induction, and treatment of postpartum hemorrhage.

• Absorption: Rapidly absorbed after oral, sublingual, buccal, or vaginal administration.
• Bioavailability:
• Oral: ~88%
• Sublingual: Faster peak levels, higher bioavailability than oral
• Vaginal: Slower onset but prolonged effect
• Onset of action:
• Oral/sublingual: ~30 minutes
• Vaginal: ~60–90 minutes
• Peak plasma concentration:
• Oral: ~12–30 minutes
• Protein binding: ~85%
• Metabolism: Rapidly de-esterified to its active metabolite, misoprostol acid (active form).
• Half-life: ~20–40 minutes.
• Excretion: Primarily renal as metabolites.

• Pregnancy:
• Former FDA Category X (contraindicated for ulcer prevention in pregnancy due to abortifacient properties).
• In reproductive health, used intentionally for abortion or labor induction; contraindicated if pregnancy continuation is desired.
• Lactation:
• Excreted into breast milk in small amounts.
• Generally considered safe during breastfeeding, especially in single postpartum doses (e.g., for PPH).
• Monitor infant for gastrointestinal symptoms (e.g., diarrhea) if repeated dosing is needed.
• Caution advised in repeated or high-dose use during lactation.

• Primary Class: Prostaglandin analog
• Subclass: Synthetic prostaglandin E1 (PGE1) analog
• Used as: Cytoprotective agent, abortifacient, uterotonic

• Known hypersensitivity to misoprostol or prostaglandins
• Pregnancy (if used for ulcer prevention or GI indications)
• Prior cesarean section or uterine surgery (relative contraindication for induction)
• Suspected or confirmed ectopic pregnancy (when used for medical abortion)
• Unexplained vaginal bleeding without diagnosis
• Inflammatory bowel disease (caution due to potential exacerbation)

• Black Box Warning (U.S.):
• Should not be used to reduce NSAID-induced ulcers in pregnant women.
• May cause abortion, premature birth, or birth defects.
• Uterine rupture risk: Especially with high doses or in women with prior uterine surgery.
• Severe diarrhea and dehydration: Monitor fluid status, especially in elderly and renal-impaired patients.
• Hypotension and chills/fever: Reported with high rectal or vaginal doses.
• Incomplete abortion or hemorrhage: Requires medical follow-up and ultrasound.
• Use only under medical supervision for reproductive indications.

Monitoring:

• Uterine activity, bleeding, fetal status (in obstetric use)
• GI symptoms and hydration (in ulcer prevention)

Common (≥10%):

• GI: Diarrhea, abdominal pain, nausea, vomiting, flatulence
• Reproductive: Uterine cramping, bleeding, chills, shivering
• General: Fever, headache

Less Common (<10%):

• Dizziness, back pain, fatigue

Serious/Rare:

• Uterine rupture (especially with previous uterine scar)
• Severe hemorrhage
• Anaphylaxis (rare)
• Severe dehydration or electrolyte imbalance due to prolonged diarrhea

Timing:

• GI symptoms often begin within 1–2 hours of dosing.
• Uterine effects begin within 30–90 minutes depending on route.

• NSAIDs: No direct interaction; used to counteract GI toxicity of NSAIDs.
• Oxytocin: Avoid concurrent use within 4 hours due to risk of excessive uterine stimulation.
• Magnesium-containing antacids: May increase misoprostol-induced diarrhea.

Enzyme Systems:

• Not significantly affected by CYP450 metabolism.
• Minimal hepatic enzyme interaction.

Food Interactions:

• Taking misoprostol with food reduces GI upset.

• WHO (2023): Endorses misoprostol as essential medicine for medical abortion, postpartum hemorrhage, and miscarriage management in low-resource settings.
• FIGO and ACOG (2022–2024): Reaffirmed evidence-based dosing for misoprostol in medical abortion and PPH.
• FDA Labeling: Continues black box warning regarding teratogenicity when used outside reproductive indications.
• Updated dosing protocols: Emphasize route-specific regimens (vaginal vs sublingual) for improved efficacy and safety.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Protect from moisture; keep in tightly closed container.
• Light protection: Store away from light; blister packs should remain sealed until use.
• Handling precautions: Wash hands after handling. Avoid exposure to pregnant women unless used intentionally for pregnancy termination or labor induction.
• No reconstitution required. Stable in tablet form; do not crush unless directed.