DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ATAZANAVIR

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIQT concern

Severity Score:3.0

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

WARNINGS AND PRECAUTIONS
Cardiac Conduction Abnormalities
Atazanavir has been shown to prolong the PR interval of the electrocardiogram in some patients. In healthy volunteers and in patients, abnormalities in atrioventricular (AV) conduction were asymptomatic and generally limited to first-degree AV block. There have been reports of second-degree AV block and other conduction abnormalities [see Adverse Reactions ( 6.2) and Overdosage ( 10) ]. In clinical trials that included electrocardiograms, asymptomatic first-degree AV block was observed in 5.9% of atazanavir-treated patients (n=920), 5.2% of lopinavir/ritonavir-treated patients (n=252), 10.4% of nelfinavir-treated patients (n=48), and 3.0% of efavirenz-treated patients (n=329). In Study AI424-045, asymptomatic first-degree AV block was observed in 5% (6/118) of atazanavir/ritonavir-treated patients and 5% (6/116) of lopinavir/ritonavir-treated patients who had on-study electrocardiogram measurements. Because of limited clinical experience in patients with preexisting conduction system disease (eg, marked first-degree AV block or second- or third-degree AV block). ECG monitoring should be considered in these patients. [See Clinical Pharmacology ( 12.2) .]
DRUG INTERACTIONS
ADVERSE REACTIONS
Postmarketing Experience
Cardiovascular System: second-degree AV block, third-degree AV block, left bundle branch block, QTc prolongation [see Warnings and Precautions ( 5.1) ]
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
Concentration- and dose-dependent prolongation of the PR interval in the electrocardiogram has been observed in healthy volunteers receiving atazanavir. In a placebo-controlled study (AI424-076), the mean (±SD) maximum change in PR interval from the predose value was 24 (±15) msec following oral dosing with 400 mg of atazanavir (n=65) compared to 13 (±11) msec following dosing with placebo (n=67). The PR interval prolongations in this study were asymptomatic. There is limited information on the potential for a pharmacodynamic interaction in humans between atazanavir and other drugs that prolong the PR interval of the electrocardiogram. [See Warnings and Precautions ( 5.1) .]
Electrocardiographic effects of atazanavir were determined in a clinical pharmacology study of 72 healthy subjects. Oral doses of 400 mg (maximum recommended dosage) and 800 mg (twice the maximum recommended dosage) were compared with placebo; there was no concentration-dependent effect of atazanavir on the QTc interval (using Fridericia's correction). In 1793 HIV-infected patients receiving antiretroviral regimens, QTc prolongation was comparable in the atazanavir and comparator regimens. No atazanavir-treated healthy subject or HIV-infected patient in clinical trials had a QTc interval >500 msec. [See Warnings and Precautions ( 5.1) .]

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24065

Other ADRs

9847

38371740

Odds Ratio = 4.373

Drug Property Information

ATC Code(s):

J05AE08 - atazanavir

J05AE0 -
J05AE - Protease inhibitors
J05A - DIRECT ACTING ANTIVIRALS
J05 - ANTIVIRALS FOR SYSTEMIC USE
J - ANTIINFECTIVES FOR SYSTEMIC USE

Active Ingredient:ATAZANAVIR SULFATE

Active Ingredient UNII:4MT4VIE29P

Drugbank ID:DB01072

PubChem Compound:148192

CTD ID:D000069446

PharmGKB:PA10251

CAS Number:198904-31-3

Dosage Form(s):capsule, gelatin coated

Route(s) Of Administrator:oral

Daily Dose:

300.0 mg/day J05AE08

Chemical Structure:

SMILE Code:
COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC1=CC=C(C=C1)C1=CC=CC=N1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C

Reference

1: Effect of COVID-19 medications on corrected QT interval and induction of torsade de pointes: Results of a multicenter national survey.

[Haghjoo Majid,Golipra Reza,Kheirkhah Jalal,Golabchi Allahyar,Shahabi Javad,Oni-Heris Saeed,Sami Ramin,Tajmirriahi Marzieh,Saravi Mehrdad,Khatami Mozhdeh,Varnasseri Mehran,Kiarsi Mohammadreza,Hejazi Seyed Fakhreddin,Yousefzadeh Rahaghi Mojtaba,Taherkhani Maryam,Ashraf Haleh,Keshmiri Mohammad Sadegh,Akbarzadeh Mohammad Ali,Bozorgi Ali,Mottaghizadeh Fateme,Hedayat Behnam,Heidarali Mona,Hajhossein Talasaz Azita]
Int J Clin Pract,2021 Mar 24;e14182. PMID: 33759318

2: Emerging and experimental treatments for COVID-19 and drug interactions with psychotropic agents.

[Bishara Delia,Kalafatis Chris,Taylor David]
Ther Adv Psychopharmacol,2020 Jun 22;10:2045125320935306. PMID: 32612804

3: Monomorphic ventricular tachycardia due to protease inhibitor intoxication by atazanavir.

[Kim Byunghyun,Kim Kyung Su]
Clin Exp Emerg Med,2018 Jun;5(2):131-134. PMID: 29706057

4: Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias.

[Cubeddu Luigi X]
Curr Cardiol Rev,2016;12(2):141-54. PMID: 26926294

5: Atazanavir induced first degree atrioventricular block and ventricular tachycardia: a case report.

[Santimaleeworagun Wichai,Pattharachayakul Suthipom,Chusri Sarunyou,Chayagul Pantip]
J Med Assoc Thai,2013 Apr;96(4):501-3. PMID: 23691707

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