Misoprostol for Ulcer Prevention

Misoprostol is a synthetic prostaglandin E1 analogue that restores the mucosal protection lost during NSAID therapy. It is used to prevent NSAID-induced gastric and duodenal ulcers. It is absolutely contraindicated in pregnancy because it causes uterine contraction and abortion. This article covers ulcer prevention only.

Classification. Prostaglandin E1 analogue; gastric cytoprotective agent.

Mechanism. Binds EP receptors on parietal cells to reduce acid secretion and stimulates mucus and bicarbonate secretion and mucosal blood flow. It replaces prostaglandins whose synthesis is inhibited by NSAIDs.

Pharmacodynamics. Antisecretory effect is dose related and appears within 30 minutes, lasting 3 to 6 hours. Uterotonic activity occurs at the same doses.

Pharmacokinetics. Rapidly absorbed and de-esterified to the active misoprostol acid. Peak level is reached in about 30 minutes and is reduced and delayed by food. Half-life of the active metabolite is 20 to 40 minutes. About 80% of metabolites are excreted in urine.

Adult oral doses.

Prevention of NSAID-induced gastric and duodenal ulcer.

• 200 micrograms four times daily with food and at bedtime for as long as the NSAID is continued.

• If 200 micrograms causes intolerable diarrhoea, reduce to 100 micrograms four times daily or 200 micrograms twice daily; efficacy may fall.

• Maximum 800 micrograms daily.

• Use in those at raised risk: age over 65, previous ulcer or bleed, concurrent anticoagulant, antiplatelet or corticosteroid.

• The combination of misoprostol with diclofenac in a single tablet exists in some markets; check product contents.

Treatment of NSAID-associated ulcer. 200 micrograms four times daily for 4 to 8 weeks. A PPI is preferred because it heals ulcers with fewer adverse effects.

Positioning. A PPI at usual ulcer-prevention doses is better tolerated and at least as effective, so misoprostol is reserved for patients who cannot take a PPI.

Children. Not established for ulcer prevention.

Contraindications.

• Pregnancy, and suspected pregnancy: abortion, premature birth, uterine rupture and birth defects (Moebius syndrome, limb defects).

• Hypersensitivity to prostaglandins.

• Women of childbearing age who are not using effective contraception.

Common adverse effects. Diarrhoea (dose related, in up to 30% to 40%), abdominal pain, flatulence, nausea, headache and dyspepsia.

Serious adverse effects.

• Uterine bleeding, intermenstrual spotting, menorrhagia and postmenopausal bleeding.

• Spontaneous abortion and congenital malformation if taken in pregnancy.

• Severe diarrhoea with dehydration.

• Hypotension in susceptible patients with cerebrovascular or coronary disease.

• Flare of inflammatory bowel disease.

Major interactions.

• Magnesium-containing antacids worsen diarrhoea; use aluminium-containing or calcium antacids if an antacid is needed.

• NSAIDs: the combination is intended and does not reduce NSAID efficacy.

• Other agents causing diarrhoea increase fluid loss.

Special groups.

• Pregnancy: contraindicated.

• Women of childbearing age: before starting, confirm a negative pregnancy test, counsel on contraception and start on the second or third day of the next normal menstrual period.

• Breastfeeding: avoid; the active metabolite enters milk and may cause infant diarrhoea.

• Older adults: no dose change; assess hydration if diarrhoea occurs.

• Kidney impairment: no routine adjustment; start with 100 micrograms four times daily if tolerance is a concern.

• Liver impairment: no adjustment.

• Inflammatory bowel disease: avoid or use with caution.

Formulations. Tablets 200 micrograms (some markets also 100 micrograms).

Administration. Take with meals and at bedtime. Swallow whole with water. Taking with food reduces diarrhoea. Do not use magnesium-containing antacids to treat dyspepsia.

Baseline. Pregnancy test in women who can conceive. Counsel on contraception during treatment and for at least 1 month after stopping.

Monitoring.

• Diarrhoea frequency and hydration, particularly in older adults.

• Menstrual and abnormal vaginal bleeding.

• Review the NSAID indication and whether it can be stopped or replaced.

Therapeutic drug monitoring. Not applicable.

Stopping. No taper is needed. Stop if diarrhoea persists for over 1 week, if bleeding develops, or if pregnancy is suspected.

Referral and escalation. Seek urgent review for suspected pregnancy during use, vaginal bleeding, severe diarrhoea or alarm features such as melaena, haematemesis and anaemia.