DIQTA 1.0: Drug-Induced QT Prolongation Atlas

VALBENAZINE

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
QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA concentrations may be higher and QT prolongation clinically significant [see Clinical Pharmacology (12.2)]. For patients who are CYP2D6 poor metabolizers or are taking a strong CYP2D6 inhibitor, dose reduction may be necessary. For patients taking a strong CYP3A4 inhibitor, reduce the dose of INGREZZA to 40 mg once daily [see Dosage and Administration (2.3, 2.4)]. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.
ADVERSE REACTIONS
The following adverse reactions are discussed in more detail in other sections of the labeling:
Hypersensitivity [see Contraindications (4)]
Somnolence [see Warnings and Precautions (5.1)]
QT Prolongation [see Warnings and Precautions (5.2)]
Parkinsonism [see Warnings and Precautions (5.3)]
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
INGREZZA may cause an increase in the corrected QT interval in patients who are CYP2D6 poor metabolizers or who are taking a strong CYP2D6 or CYP3A4 inhibitor. An exposure-response analysis of clinical data from two healthy volunteer studies revealed increased QTc interval with higher plasma concentrations of the active metabolite. Based on this model, patients taking an INGREZZA 80 mg dose with increased exposure to the metabolite (e.g., being a CYP2D6 poor metabolizer) may have a mean QT prolongation of 11.7 msec (14.7 msec upper bound of double-sided 90% CI) as compared to otherwise healthy volunteers given INGREZZA, who had a mean QT prolongation of 6.7 msec (8.4 msec) [see Warnings and Precautions (5.2)].
PATIENT COUNSELING INFORMATION
Prolongation of the QT Interval
Inform patients to consult their physician immediately if they feel faint, lose consciousness, or have heart palpitations [see Warnings and Precautions (5.2)]. Advise patients to inform physicians that they are taking INGREZZA before any new drug is taken.
PATIENT PACKAGE INSERT
Before taking INGREZZA, tell your healthcare provider about all of your medical conditions including if you:
have liver problems
have heart disease that is not stable, have heart failure or recently had a heart attack
have an irregular heart rhythm or heartbeat (QT prolongation, heart arrhythmia)

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24065

Other ADRs

24806

38356781

Odds Ratio = 1.735

Drug Property Information

ATC Code(s):

N07XX13 - valbenazine

N07XX - Other nervous system drugs
N07X - OTHER NERVOUS SYSTEM DRUGS
N07 - OTHER NERVOUS SYSTEM DRUGS
N - NERVOUS SYSTEM

Active Ingredient:VALBENAZINE

Active Ingredient UNII:54K37P50KH

Drugbank ID:DB11915

PubChem Compound:24795069

CTD ID:C000603978

PharmGKB:

CAS Number:1025504-45-3

Dosage Form(s):capsule; kit

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
COC1=C(OC)C=C2[C@H]3C[C@@H](OC(=O)[C@@H](N)C(C)C)[C@H](CC(C)C)CN3CCC2=C1

Reference

1: Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.

[Thai-Cuarto Dao,O'Brien Christopher F,Jimenez Roland,Liang Grace S,Burke Joshua]
Drug Saf,2018 Apr;41(4):429-440. PMID: 29218680

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