DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ALFUZOSIN 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

WARNINGS AND PRECAUTIONS
Patients with Congenital or Acquired QT Prolongation
Use with caution in patients with acquired or congenital QT prolongation or who are taking medications that prolong the QT interval [see CLINICAL PHARMACOLOGY (12.2)].
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of 10 mg and 40 mg alfuzosin on QT interval was evaluated in a double-blind, randomized, placebo and active-controlled (moxifloxacin 400 mg), 4-way crossover single dose study in 45 healthy white male subjects aged 19 to 45 years. The QT interval was measured at the time of peak alfuzosin plasma concentrations. The 40 mg dose of alfuzosin was chosen because this dose achieves higher blood levels than those achieved with the co-administration of alfuzosin hydrochloride extended-release tablets and ketoconazole 400 mg. Table 3 summarizes the effect on uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia, population-specific and subject-specific correction methods) at the time of peak alfuzosin plasma concentrations. No single one of these correction methodologies is known to be more valid. The mean change of heart rate associated with a 10 mg dose of alfuzosin in this study was 5.2 beats/minute and 5.8 beats/minute with 40 mg alfuzosin. The change in heart rate with moxifloxacin was 2.8 beats/minute.
The QT effect appeared greater for 40 mg compared to 10 mg alfuzosin. The effect of the highest alfuzosin dose (four times the therapeutic dose) studied did not appear as large as that of the active control moxifloxacin at its therapeutic dose. This study, however, was not designed to make direct statistical comparisons between the drugs or the dose levels. There has been no signal of Torsade de Pointes in the extensive post-marketing experience with alfuzosin outside the United States.
A separate post-marketing QT study evaluated the effect of the co-administration of 10 mg alfuzosin with a drug of similar QT effect size. In this study, the mean placebo-subtracted QTcF increase of alfuzosin 10 mg alone was 1.9 msec (upperbound 95% CI, 5.5 msec). The concomitant administration of the two drugs showed an increased QT effect when compared with either drug alone. This QTcF increase [5.9 msec (UB 95% CI, 9.4 msec)] was not more than additive. Although this study was not designed to make direct statistical comparisons between drugs, the QT increase with both drugs given together appeared to be lower than the QTcF increase seen with the positive control moxifloxacin 400 mg [10.2 msec (UB 95% CI, 13.8 msec)]. The clinical impact of these QTc changes is unknown.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24082

Other ADRs

4109

38377478

Odds Ratio = 3.879

Drug Property Information

ATC Code(s):

G04CA01 - alfuzosin hydrochloride

G04CA - Alpha-adrenoreceptor antagonists
G04C - DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
G04 - UROLOGICALS
G - GENITO URINARY SYSTEM AND SEX HORMONES

Active Ingredient:ALFUZOSIN HYDROCHLORIDE

Active Ingredient UNII:75046A1XTN

Drugbank ID:DB00346

PubChem Compound:2092

CTD ID: C047638

PharmGKB:PA164774795

CAS Number:81403-80-7

Dosage Form(s):tablet, film coated, extended release

Route(s) Of Administrator:oral

Daily Dose:

7.5 mg/day G04CA01

Chemical Structure:

SMILE Code:
COC1=CC2=C(C=C1OC)C(N)=NC(=N2)N(C)CCCNC(=O)C1CCCO1

Reference

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