What are the side effects of Misoprostol (prostaglandin E1 analogue)?

Side Effects of Misoprostol (Prostaglandin E1 Analogue)

Misoprostol commonly causes gastrointestinal side effects, with diarrhea and abdominal pain being the most frequent adverse reactions, occurring in 13-40% of patients taking standard doses. 1, 2

Common Gastrointestinal Side Effects

• Diarrhea is the most common side effect, occurring in 13-40% of patients taking misoprostol at doses of 800 mcg daily, and is dose-related 1, 2
• Diarrhea typically develops early in treatment (after 1-3 days), is usually self-limiting (often resolving after 8 days), but sometimes requires discontinuation (in about 2% of patients) 1
• Abdominal pain/cramps occur in 13-20% of patients in NSAID trials 1, 2
• Nausea (3.2%), flatulence (2.9%), dyspepsia (2.0%), vomiting (1.3%), and constipation (1.1%) are also commonly reported 1, 2
• Rare instances of profound diarrhea leading to severe dehydration have been reported 1, 2

Managing Gastrointestinal Side Effects

• The incidence of diarrhea can be minimized by administering misoprostol after meals and at bedtime 1, 2
• Avoiding co-administration with magnesium-containing antacids can reduce diarrhea incidence 1, 2
• Patients with underlying conditions such as inflammatory bowel disease or those for whom dehydration would be dangerous should be monitored carefully 1, 2

Gynecological Side Effects

• Women taking misoprostol may experience gynecological disorders including 1, 2:
  • Spotting (0.7%)
  • Menstrual cramps (0.6%)
  • Hypermenorrhea (excessive menstrual bleeding) (0.5%)
  • Menstrual disorders (0.3%)
  • Dysmenorrhea (painful periods) (0.1%)
• Postmenopausal vaginal bleeding may occur and requires diagnostic workup to rule out gynecological pathology 1, 2
• Misoprostol is contraindicated in pregnancy due to its abortifacient properties 1, 2

Cardiovascular Side Effects

• Misoprostol can cause hypertension, with studies showing increased systolic blood pressure ≥140 mmHg (33% vs 25% with placebo) and diastolic blood pressure ≥90 mmHg (10.5% vs 3.0% with placebo) 3
• Other reported cardiovascular effects include chest pain, edema, diaphoresis, hypotension, arrhythmia, phlebitis, increased cardiac enzymes, syncope, and rarely myocardial infarction 1, 2
• Thromboembolic events such as pulmonary embolism, arterial thrombosis, and cerebrovascular accidents have been reported, though causal relationships have not been established 1, 2

Temperature-Related Side Effects

• Shivering is significantly more common with misoprostol (44%) compared to placebo (11%) 3
• Pyrexia (fever ≥37.8°C) occurs in 38% of patients taking misoprostol compared to 6% with placebo 3

Other Reported Side Effects

• Headache (2.4%) 1, 2
• Skin reactions: rash, dermatitis, alopecia, pallor 1, 2
• Respiratory: upper respiratory tract infection, bronchitis, bronchospasm, dyspnea, pneumonia, epistaxis 1, 2
• Nervous system/psychiatric: anxiety, changes in appetite, depression, drowsiness, dizziness, confusion 1, 2
• Musculoskeletal: arthralgia, myalgia, muscle cramps, stiffness, back pain 1, 2
• Hematologic: anemia, abnormal differential, thrombocytopenia, purpura 1, 2

Special Considerations

• Elderly patients (65 years or older) show no significant differences in safety profile compared to younger patients 1, 2
• Patients with inflammatory bowel disease require careful monitoring due to risk of exacerbation 1, 2
• Misoprostol is contraindicated in pregnant women due to risk of abortion, premature birth, or birth defects 1
• Extreme overdose (12 mg) has been associated with severe complications including gastrointestinal necrosis and death in a case report 4

Clinical Context

• When used for NSAID-induced ulcer prevention, misoprostol (200 μg four times daily) has been shown to reduce ulcer complications by approximately 40%, but side effects lead to higher withdrawal rates compared to proton pump inhibitors 5
• The majority of patients can take misoprostol without significant problems, suggesting that individual tolerance varies 5
• For patients who cannot tolerate standard doses, combination of half-dose misoprostol with an H2-receptor antagonist or PPI might provide effective preventive therapy with fewer side effects 5

By understanding these side effects and implementing appropriate management strategies, clinicians can optimize the use of misoprostol while minimizing adverse reactions.