DIQTA 1.0: Drug-Induced QT Prolongation Atlas

FEXOFENADINE 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
Erythromycin and Ketoconazole
Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co–administration of fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine in healthy adult subjects. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies in healthy adult subjects, fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was co-administered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy adult subjects (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine hydrochloride alone or in combination with either erythromycin or ketoconazole.
CLINICAL PHARMACOLOGY
Pharmacodynamics
No statistically significant increase in mean QTc interval compared to placebo was observed in 714 adult subjects with seasonal allergic rhinitis given fexofenadine hydrochloride capsules in doses of 60 to 240 mg twice daily for 2 weeks. Pediatric subjects from 2 placebo- controlled trials (n=855) treated with up to 60 mg fexofenadine hydrochloride twice daily demonstrated no significant treatment- or dose-related increases in QTc. In addition, no statistically significant increase in mean QTc interval compared to placebo was observed in 40 healthy adult subjects given fexofenadine hydrochloride as an oral solution at doses up to 400 mg twice daily for 6 days, or in 230 healthy adult subjects given fexofenadine hydrochloride 240 mg once daily for 1 year. In subjects with chronic idiopathic urticaria, there were no clinically relevant differences for any ECG intervals, including QTc, between those treated with fexofenadine hydrochloride 180 mg once daily (n = 163) and those treated with placebo (n = 91) for 4 weeks.
NONCLINICAL TOXICOLOGY
Animal Toxicology and/or Pharmacology
In dogs (30 mg/kg/orally twice daily for 5 days) and rabbits (10 mg/kg, intravenously over 1 hour), fexofenadine hydrochloride did not prolong QTc. In dogs, the plasma fexofenadine concentration was approximately 9 times the therapeutic plasma concentrations in adults receiving the maximum recommended human daily oral dose of 180 mg. In rabbits, the plasma fexofenadine concentration was approximately 20 times the therapeutic plasma concentration in adults receiving the maximum recommended human daily oral dose of 180 mg. No effect was observed on calcium channel current, delayed K+ channel current, or action potential duration in guinea pig myocytes, or on the delayed rectifier K+ channel cloned from human heart at concentrations up to 1 × 10-5 M of fexofenadine.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24067

Other ADRs

36892

38344695

Odds Ratio = 1.08

Drug Property Information

ATC Code(s):

R06AX26 - fexofenadine hydrochloride

R06AX - Other antihistamines for systemic use
R06A - ANTIHISTAMINES FOR SYSTEMIC USE
R06 - ANTIHISTAMINES FOR SYSTEMIC USE
R - RESPIRATORY SYSTEM

Active Ingredient:FEXOFENADINE HYDROCHLORIDE

Active Ingredient UNII:2S068B75ZU

Drugbank ID:DB00950

PubChem Compound:3348

CTD ID:C093230

PharmGKB:PA449621

CAS Number:83799-24-0

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

120.0 mg/day R06AX26

Chemical Structure:

SMILE Code:
CC(C)(C(O)=O)C1=CC=C(C=C1)C(O)CCCN1CCC(CC1)C(O)(C1=CC=CC=C1)C1=CC=CC=C1

Reference

N/A