Alosetron
Drugs for irritable bowel syndrome
Drugs for irritable bowel syndrome
A 5-HT3 blocker for women with severe IBS with diarrhoea that has not responded to other care. It can cause ischaemic colitis and severe constipation.
Quick facts
- Group
- Drugs for irritable bowel syndrome
- Target
- 5-HT3 receptor (ligand-gated cation channel) on enteric neurons
- Key effects
- Constipation · Abdominal discomfort and pain · Nausea
- Monitor
- Bowel habit · Rectal bleeding
- ATC
- A03AE01
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows alosetron bound to the mouse 5-HT3A receptor, which closely resembles the human channel.
Alosetron is a potent, selective 5-HT3 receptor antagonist. 5-HT3 receptors are cation channels on enteric neurons that, when activated by serotonin, affect visceral pain, colonic transit and secretion. Blocking them modulates the enteric nervous system: transit slows, urgency and pain ease. Too much slowing explains constipation, and reduced colonic blood flow in some patients explains ischaemic colitis.
- Alosetron blocks 5-HT3 channels on enteric neurons
- Less neuronal depolarisation in the gut wall
- Colonic transit slows; urgency and pain ease
Indications
- Severe diarrhoea-predominant irritable bowel syndrome in women, chronic, with other causes excluded and no response to conventional therapy Irritable bowel syndrome →
Adverse effects
Common
- Constipation, the most common effect
- Abdominal discomfort and pain
- Nausea
- Flatulence
Contraindications
- Starting in a patient who is constipated
- History of chronic or severe constipation, intestinal obstruction, stricture, toxic megacolon, perforation or adhesions
- Ischaemic colitis, impaired intestinal circulation, thrombophlebitis or a hypercoagulable state
- Crohn's disease, ulcerative colitis, diverticulitis
- Severe hepatic impairment; use with fluvoxamine
Key interactions
- Fluvoxamine (strong CYP1A2 inhibitor)
- Much higher alosetron levels and longer half-life; contraindicated
- Moderate CYP1A2 inhibitors (fluoroquinolones, cimetidine)
- Likely higher levels; avoided unless needed
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, protease inhibitors)
- Higher exposure; used with caution
- Drugs that slow the bowel (opioids, anticholinergics)
- Higher risk of serious constipation
What is monitored
- Bowel habit: constipation means stopping at once
- Rectal bleeding, bloody diarrhoea or new abdominal pain
- Symptom control after the first weeks
Administration and safety
- Oral tablet; started at a low dose and stopped if symptoms are not controlled after a few weeks at the full dose.
- Not restarted after ischaemic colitis.
- Older, frail patients and those on bowel-slowing drugs are at higher risk of constipation complications.
Pregnancy and breastfeeding
Human data are insufficient to define a risk; animal studies showed no developmental harm.
Nursing care
- Ask about constipation, past bowel obstruction, IBD, diverticulitis, clotting disorders and liver disease before starting.
- Check the medication list for fluvoxamine and other CYP1A2 inhibitors.
- Teach the patient to stop the drug and call at once for constipation, rectal bleeding, bloody diarrhoea or worsening pain.
- Give and explain the medication guide.
Pharmacokinetics
- Absorption
- Rapidly absorbed orally; food lowers absorption somewhat
- Metabolism
- Mainly hepatic CYP1A2, with minor CYP3A4 and CYP2C9
- Half-life
- Short, about one and a half hours
Test yourself
Think of the answer, then tap the question to see it.
Which patients is alosetron limited to?
Women with severe, chronic diarrhoea-predominant IBS who did not respond to conventional therapy.
A patient on alosetron has rectal bleeding. What is suspected and what is done?
Ischaemic colitis; the drug is stopped immediately and not restarted.
Which antidepressant is contraindicated with alosetron and why?
Fluvoxamine, a strong CYP1A2 inhibitor that greatly raises alosetron levels.
Connections
← Back to the class: Drugs for irritable bowel syndrome
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ALOSETRON HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2025); Alosetron: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); RCSB PDB - 6W1J: Cryo-EM structure of 5HT3A receptor in presence of Alosetron (RCSB Protein Data Bank, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.