DIQTA 1.0: Drug-Induced QT Prolongation Atlas

DARIFENACIN

Classification:Ambiguous

Severity Score:1.0

CLINICAL PHARMACOLOGY
Electrophysiology
The effect of six-day treatment of 15-mg and 75-mg ENABLEX on QT/QTc interval was evaluated in a multiple-dose, double-blind, randomized, placebo- and active-controlled (moxifloxacin 400 mg) parallel-arm design study in 179 healthy adults (44% male, 56% female) aged 18 to 65. Subjects included 18% PMs and 82% EMs. The QT interval was measured over a 24-hour period both predosing and at steady state. The 75-mg ENABLEX dose was chosen because this achieves exposure similar to that observed in CYP2D6 poor metabolizers administered the highest recommended dose (15 mg) of darifenacin in the presence of a potent CYP3A4 inhibitor. At the doses studied, ENABLEX did not result in QT/QTc interval prolongation at any time during the steady state, while moxifloxacin treatment resulted in a mean increase from baseline QTcF of about 7.0 msec when compared to placebo. In this study, darifenacin 15-mg and 75-mg doses demonstrated a mean heart rate change of 3.1 and 1.3 bpm, respectively, when compared to placebo. However, in the Phase II/III clinical studies, the change in median HR following treatment with ENABLEX was no different from placebo.

Current Drug

Other Drugs

QT Prolongation

24090

Other ADRs

4241

38377346

Odds Ratio = 0.752

ATC Code(s):

Active Ingredient:DARIFENACIN

Active Ingredient UNII:APG9819VLM

Drugbank ID:DB00496

PubChem Compound:444031

CTD ID:C101207

CAS Number:133099-04-4

Dosage Form(s):tablet, extended release

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1

N/A