DIQTA 1.0: Drug-Induced QT Prolongation Atlas

AMIODARONE HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Most-DIQT concern

Severity Score:4.0

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

WARNINGS
Proarrhythmia
Like all antiarrhythmic agents, amiodarone HCl injection may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation by amiodarone HCl injection of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving amiodarone HCl injection, torsade de pointes or new-onset VF occurred infrequently (less than 2%). Patients should be monitored for QTc prolongation during infusion with amiodarone HCl injection. Combination of amiodarone with other antiarrhythmic therapy that prolongs the QTc should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.
Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly (see DRUG INTERACTIONS, OTHER REPORTED INTERACTIONS WITH AMIODARONE).
The need to coadminister amiodarone with any other drug known to prolong the QTc interval must be based on a careful assessment of the potential risks and benefits of doing so for each patient.
A careful assessment of the potential risks and benefits of administering amiodarone HCl injection must be made in patients with thyroid dysfunction due to the possibility of arrhythmia breakthrough or exacerbation of arrhythmia, which may result in death, in these patients.
PRECAUTIONS
Drug Interactions
Loratadine, a non-sedating antihistaminic, is metabolized primarily by CYP3A4. QT interval prolongation and torsade de pointes have been reported with the co-administration of loratadine and amiodarone.
Trazodone, an antidepressant, is metabolized primarily by CYP3A4. QT interval prolongation and torsade de pointes have been reported with the co-administration of trazodone and amiodarone.
Disopyramide increases QT prolongation which could cause arrhythmia.
Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly (see PRECAUTIONS, PROARRHYTHMIA).
Electrolyte Disturbances
Patients with hypokalemia or hypomagnesemia should have the condition corrected whenever possible before being treated with amiodarone HCl injection, as these disorders can exaggerate the degree of QTc prolongation and increase the potential for TdP. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or in patients receiving concomitant diuretics.
ADVERSE REACTIONS
Other treatment-emergent possibly drug-related adverse events reported in less than 2% of patients receiving amiodarone HCl injection in controlled and uncontrolled studies included the following: abnormal kidney function, atrial fibrillation, diarrhea, increased ALT, increased AST, lung edema, nodal arrhythmia, prolonged QT interval, respiratory disorder, shock, sinus bradycardia, Stevens-Johnson syndrome, thrombocytopenia, VF, and vomiting.
CLINICAL PHARMACOLOGY
Mechanisms of Action
Amiodarone HCl Injection administration prolongs intranodal conduction (Atrial-His, AH) and refractoriness of the atrioventricular node (ERP AVN), but has little or no effect on sinus cycle length (SCL), refractoriness of the right atrium and right ventricle (ERP RA and ERP RV), repolarization (QTc), intraventricular conduction (QRS), and infranodal conduction (His-ventricular, HV). A comparison of the electrophysiologic effects of amiodarone HCl injection and oral amiodarone is shown in the table below.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

531

23561

Other ADRs

62629

38318958

Odds Ratio = 13.79

Drug Property Information

ATC Code(s):

C01BD01 - amiodarone hydrochloride

C01BD0 -
C01BD - "Antiarrhythmics, class III"
C01B - "ANTIARRHYTHMICS, CLASS I AND III"
C01 - CARDIAC THERAPY
C - CARDIOVASCULAR SYSTEM

Active Ingredient:AMIODARONE HYDROCHLORIDE

Active Ingredient UNII:976728SY6Z

Drugbank ID:DB01118

PubChem Compound:2157

CTD ID:D000638

PharmGKB:PA448383

CAS Number:1951-25-3

Dosage Form(s):injection, solution

Route(s) Of Administrator:intravenous

Daily Dose:

200.0 mg/day C01BD01

Chemical Structure:

SMILE Code:
CCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=C(O1)C=CC=C2

Reference

1: Anti-atrial Fibrillatory Versus Proarrhythmic Potentials of Amiodarone: A New Protocol for Safety Evaluation In Vivo.

[Matsukura Suchitra,Nakamura Yuji,Cao Xin,Wada Takeshi,Izumi-Nakaseko Hiroko,Ando Kentaro,Sugiyama Atsushi]
Cardiovasc Toxicol,2017 Apr;17(2):157-162. PMID: 27040813

2: Disopyramide-induced Torsade de Pointes.

[Tzivoni D,Keren A,Stern S,Gottlieb S]
Arch Intern Med,1981 Jun;141(7):946-7. PMID: 7235820

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