BLACK BOX WARNING
- serious GI adverse events including ischemic colitis and severe constipation resulting in hospitalization, surgery, and death; prescribe only through a Risk Evaluation and Mitigation Strategy (REMS) program
alosetron
Brand: Lotronex
⚠ BBW Prototype: ondansetron
Drug Class: 5-HT3 receptor antagonist (GI-selective)
Drug Family: GI agent
Subclass: selective 5-HT3 antagonist for IBS
Organ Systems: gastrointestinal
Mechanism of Action
Selectively antagonizes 5-HT3 receptors in the enteric nervous system and on visceral afferent neurons. This slows colonic transit, reduces intestinal secretion, and decreases visceral hypersensitivity, addressing both the diarrhea and pain components of IBS-D.
5-HT3 receptors (enteric nervous system and visceral afferents)
Indications
- severe diarrhea-predominant IBS (IBS-D) in women who have not responded to conventional therapy
Contraindications
- IBS with constipation
- chronic constipation
- Crohn's disease
- ulcerative colitis
- ischemic colitis history
- hypercoagulable state
- severe hepatic impairment
Adverse Effects
Common
- constipation (up to 29%)
- abdominal pain
Serious
- ischemic colitis
- severe constipation requiring hospitalization or surgery
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~50–60%; affected by gender (women have higher exposure) |
| Distribution | 82% protein bound |
| Metabolism | hepatic via CYP1A2, CYP3A4, CYP2C9 |
| Excretion | renal (~73%) |
| Half-life | 1.5 hours |
| Onset | days |
| Peak | 1 hour |
| Duration | continuous dosing |
| Protein Binding | 82% |
| Vd | 65–95 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| fluvoxamine | CYP1A2 inhibition increases alosetron exposure 6-fold; contraindicated | contraindicated |
| strong CYP1A2 inhibitors | markedly increased alosetron levels | major |
Nursing Considerations
- Only prescribers enrolled in the Lotronex REMS program may prescribe alosetron; verify enrollment status.
- Discontinue immediately at first signs of ischemic colitis (rectal bleeding, bloody diarrhea, new or worsening abdominal pain); do not reinstate.
- Instruct patient to stop use if constipation develops and resume only when constipation resolves at the lowest dose.
- Approved only for women with severe IBS-D unresponsive to conventional therapy — confirm severity and refractoriness before prescribing.
Clinical Pearls
- Alosetron was voluntarily withdrawn from the market in 2000 due to serious GI adverse events and re-introduced in 2002 under a REMS program with restricted prescribing — it is one of the few drugs reintroduced under a formal risk management program.
- Its selectivity for 5-HT3 receptors in the enteric nervous system rather than the CTZ distinguishes its GI-targeted effects from antiemetic 5-HT3 antagonists.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.