DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ALOSETRON HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Ambiguous

Severity Score:1.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

DRUG INTERACTIONS
Other CYP Enzymes
In vitro human liver microsome studies and an in vivo metabolic probe study demonstrated that alosetron did not inhibit CYP enzymes 3A4, 2C9, or 2C19. In vitro at total drug concentrations 27-fold higher than peak plasma concentrations observed with the 1 mg dose, alosetron inhibited CYP enzymes 1A2 (60%) and 2E1 (50%). In an in vivo metabolic probe study, alosetron did not inhibit CYP2E1 but did produce 30% inhibition of both CYP1A2 and N-acetyltransferase. Although not studied with alosetron, inhibition of N-acetyltransferase may have clinically relevant consequences for drugs such as isoniazid, procainamide, and hydralazine. The effect on CYP1A2 was explored further in a clinical interaction study with theophylline and no effect on metabolism was observed. Another study showed that alosetron had no clinically significant effect on plasma concentrations of the oral contraceptive agents ethinyl estradiol and levonorgestrel (CYP3A4 substrates). A clinical interaction study was also conducted with alosetron and the CYP3A4 substrate cisapride. No significant effects on cisapride metabolism or QT interval were noted. The effects of alosetron on monoamine oxidases and on intestinal first pass secondary to high intraluminal concentrations have not been examined. Based on the above data from in vitro and in vivo studies, it is unlikely that alosetron will inhibit the hepatic metabolic clearance of drugs metabolized by the CYP enzymes 2C9, 2C19, or 2E1.
Alosetron does not appear to induce the major cytochrome P450 drug-metabolizing enzyme 3A. Alosetron also does not appear to induce CYP enzymes 2E1 or 2C19. It is not known whether alosetron might induce other enzymes.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24092

Other ADRs

1820

38379767

Odds Ratio = 0.0

Drug Property Information

ATC Code(s):

A03AE01 - alosetron hydrochloride

A03AE - Drugs acting on serotonin receptors
A03A - DRUGS FOR FUNCTIONAL BOWEL DISORDERS
A03 - DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS
A - ALIMENTARY TRACT AND METABOLISM

Active Ingredient:ALOSETRON HYDROCHLORIDE

Active Ingredient UNII:2F5R1A46YW

Drugbank ID:DB00969

PubChem Compound:2099

CTD ID:C090840

PharmGKB:PA164745502

CAS Number:122852-42-0

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

1.0 mg/day A03AE01

Chemical Structure:

SMILE Code:
CN1C2=C(C3=CC=CC=C13)C(=O)N(CC1=C(C)NC=N1)CC2

Reference

N/A