What are the side effects of misoprostol (prostaglandin E1 analogue) for expelling products of conception?

Side Effects of Misoprostol for Expelling Products of Conception

Misoprostol commonly causes diarrhea, abdominal cramping, nausea, vomiting, shivering, and fever when used for expelling products of conception, with diarrhea being the most frequent side effect that leads to treatment discontinuation in up to 20% of patients. 1

Common Side Effects

Gastrointestinal Effects

• Diarrhea: The most prevalent side effect, affecting up to 20% of patients
  • Occurs within 2-6 hours after administration
  • May persist for up to 12 hours 2
  • In a study of rheumatoid arthritis patients, 20% withdrew from misoprostol treatment within the first month due to diarrhea 1
• Nausea and vomiting: More common with oral administration than vaginal administration 3
• Abdominal cramping/pain: Peaks at 1-2 hours after oral administration and 2-3 hours after vaginal administration 3

Temperature-Related Effects

• Shivering: Very common (RR 6.4 compared to oxytocin in the first hour after administration) 2
  • Can persist up to 6 hours following delivery
• Fever/pyrexia: Occurs in up to 6% of patients 3
  • More common in the first 6 hours after administration (RR 2.8 in first hour, RR 6.3 in 2-6 hour period) 2
  • Can occasionally progress to hyperpyrexia (very high fever) 4

Less Common Side Effects

• Headache
• Dizziness
• Fatigue
• Breast tenderness (typically decreases after administration) 3

Serious Adverse Effects

Uterine-Related Complications

• Uterine tachysystole: Abnormally frequent uterine contractions
• Uterine tetany: Sustained uterine contraction
• Uterine rupture: Risk increases with:
  • Advanced gestational age
  • Prior uterine surgery (including cesarean delivery)
  • Grand multiparity 5

Other Serious Complications

• Incomplete abortion: May require additional intervention
• Bleeding: Can be significant, though misoprostol is also used to treat postpartum hemorrhage
• Infection: Rare but possible complication 6

Special Considerations

Dosage-Related Effects

• Side effects are generally dose-dependent
• Doses exceeding 800 μg are more likely to cause diarrhea and other side effects 7
• For expelling products of conception, 400 μg vaginally every 3-6 hours is considered optimal for balancing efficacy with side effects 6

Route of Administration Differences

• Oral administration: Associated with higher rates of nausea, vomiting, and diarrhea
• Vaginal administration: Associated with later onset but potentially higher peak of fever
• Pain occurs earlier with oral administration than with vaginal administration 3

Risk Mitigation Strategies

• Use the lowest effective dose to minimize side effects
• Consider prophylactic antiemetics for patients with history of severe nausea/vomiting
• Ensure adequate pain management is available
• Monitor for fever and provide antipyretics as needed
• Ensure adequate hydration, especially if diarrhea occurs
• Patients with a scarred uterus should receive lower doses to reduce risk of uterine rupture 7

Monitoring Recommendations

• Close observation for the first 6 hours after administration when most side effects peak
• Temperature monitoring for fever
• Assessment for excessive bleeding
• Evaluation of complete expulsion of products of conception

The FDA label for misoprostol emphasizes that these side effects are generally transient but can be significant enough to lead to treatment discontinuation in some patients 5. While PPIs are now the preferred agents for prophylaxis of NSAID-associated GI injury 1, misoprostol remains an important medication for gynecological indications including expulsion of products of conception.