DIQTA 1.0: Drug-Induced QT Prolongation Atlas

DESLORATADINE

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

ADVERSE REACTIONS
Clinical Trials Experience
There were no clinically meaningful changes in any electrocardiographic parameter, including the QTc interval. Only one of the 246 pediatric subjects receiving Desloratadine Oral Solution in the clinical trials discontinued treatment because of an adverse event.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Effects on QTc: Single daily doses of 45 mg were given to normal male and female volunteers for 10 days. All ECGs obtained in this study were manually read in a blinded fashion by a cardiologist. In Desloratadine-treated subjects, there was an increase in mean heart rate of 9.2 bpm relative to placebo. The QT interval was corrected for heart rate (QTc) by both the Bazett and Fridericia methods. Using the QTc (Bazett) there was a mean increase of 8.1 msec in Desloratadine-treated subjects relative to placebo. Using QTc (Fridericia) there was a mean increase of 0.4 msec in Desloratadine-treated subjects relative to placebo. No clinically relevant adverse events were reported.
[Pharmacokinetics]
Drug Interactions: In two controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) volunteers, desloratadine 7.5 mg (1.5 times the daily dose) once daily was coadministered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In three separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been coadministered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23-day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady-state conditions to normal healthy male and female volunteers. Although increased plasma concentrations (Cmax and AUC0-24 hrs) of desloratadine and 3-hydroxydesloratadine were observed (see TABLE 2), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs, and adverse events.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24055

Other ADRs

5667

38375920

Odds Ratio = 10.417

Drug Property Information

ATC Code(s):

R06AX27 - desloratadine

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

Active Ingredient:DESLORATADINE

Active Ingredient UNII:FVF865388R

Drugbank ID:DB00967

PubChem Compound:124087

CTD ID:C121345

PharmGKB:PA164776964

CAS Number:100643-71-8

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

5.0 mg/day R06AX27

Chemical Structure:

SMILE Code:
ClC1=CC2=C(C=C1)C(=C1CCNCC1)C1=C(CC2)C=CC=N1

Reference

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2: {'#text': 'Cardiac safety of second-generation H -antihistamines when updosed in chronic spontaneous urticaria.', 'sub': '1'}

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Clin Exp Allergy,2019 Dec;49(12):1615-1623. PMID: 31519068

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6: Comparative pharmacology of guinea pig cardiac myocyte and cloned hERG (I(Kr)) channel.

[Davie Christina,Pierre-Valentin Jean,Pollard Chris,Standen Nick,Mitcheson John,Alexander Paul,Thong Bob]
J Cardiovasc Electrophysiol,2004 Nov;15(11):1302-9. PMID: 15574182

7: Comparative effects of loratadine and terfenadine on cardiac K+ channels.

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J Cardiovasc Pharmacol,1997 Jul;30(1):42-54. PMID: 9268220

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