Alosetron

Alosetron

Clinical data
Trade names	Lotronex
AHFS/Drugs.com	Monograph
MedlinePlus	a601230
Pregnancy category	US: B (No risk in non-human studies)
Routes of administration	Oral (tablets)
ATC code	A03AE01 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	50–60%
Protein binding	82%
Metabolism	Hepatic (including CYP2C9, CYP3A4 and CYP1A2)
Biological half-life	1.5–1.7 hours
Excretion	Renal 73%, faecal 24%
Identifiers
IUPAC name 5-methyl-2-[(4-methyl-1H-imidazol-5-yl)methyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one
CAS Number	122852-42-0 Y
PubChem CID	2099
IUPHAR/BPS	2296
DrugBank	DB00969 Y
ChemSpider	2015 Y
UNII	13Z9HTH115
KEGG	D07129 Y
ChEBI	CHEBI:253342 Y
ChEMBL	CHEMBL1110 Y
Chemical and physical data
Formula	C17H18N4O
Molar mass	294.351 g/mol
3D model (Jmol)	Interactive image
SMILES O=C1N(CCc3c1c2ccccc2n3C)Cc4ncnc4C
InChI InChI=1S/C17H18N4O/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19) Y Key:JSWZEAMFRNKZNL-UHFFFAOYSA-N Y

Alosetron (original brand name: Lotronex LOW-trah-nex; originator: GSK) is a 5-HT₃ antagonist used for the management of severe diarrhea-predominant irritable bowel syndrome (IBS) in women only. It is currently marketed by Prometheus Laboratories Inc. (San Diego). Alosetron was withdrawn from the market in 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, but was reintroduced in 2002 with availability and use restricted.

Alosetron was originally approved by the U.S. Food and Drug Administration (FDA) on February 9, 2000, after a seven-month review. At the time of the initial approval U.S. Food and Drug Administration (FDA) reviewers found that alosetron improved symptoms in 10% to 20% of patients.

Shipment to pharmacies started in March, 2000. On July 17, a health professional filed a report with the FDA on the death of a 50-year-old woman who suffered mesenteric ischemia. The report identified alosetron as the "primary suspect" in the death.

Alosetron was withdrawn from the market voluntarily by GlaxoWellcome on November 28, 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, including 5 deaths and additional bowel surgeries. The FDA said it had reports of 49 cases of ischemic colitis and 21 cases of "severe constipation" and that ten of the 70 patients underwent surgeries and 34 others were examined at hospitals and released without surgery. Through November 17, 2000, pharmacists had filled 474,115 prescriptions for alosetron. Severe adverse events continued to be reported, with a final total of 84 instances of ischaemic colitis, 113 of severe constipation, 143 admissions to hospital, and 7 deaths.