DIQTA 1.0: Drug-Induced QT Prolongation Atlas

LOFEXIDINE HYDROCHLORIDE

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
Risk of QT Prolongation
LUCEMYRA prolongs the QT interval.
Avoid using LUCEMYRA in patients with congenital long QT syndrome.
Monitor ECG in patients with congestive heart failure, bradyarrhythmias, hepatic impairment, renal impairment, or patients taking other medicinal products that lead to QT prolongation (e.g., methadone). In patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), correct these abnormalities first, and monitor ECG upon initiation of LUCEMYRA [see DOSING AND ADMINISTRATION (2.1), ADVERSE REACTIONS (6.1), SPECIAL POPULATIONS (8.6)(8.7), CLINICAL PHARMACOLOGY (12.2)].
DRUG INTERACTIONS
Methadone
LUCEMYRA and methadone both prolong the QT interval. ECG monitoring is recommended in patients receiving methadone and LUCEMYRA [see WARNINGS AND PRECAUTIONS (5.2), CLINICAL PHARMACOLOGY (12.3)].
ADVERSE REACTIONS
Postmarketing Experience
Lofexidine is marketed in other countries for relief of opioid withdrawal symptoms. The following events have been identified during postmarketing use of lofexidine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Since lofexidine's initial market introduction in 1992, the most frequently reported postmarketing adverse event with lofexidine has been hypotension [see WARNINGS AND PRECAUTIONS (5.1)]. There has been one report of QT prolongation, bradycardia, torsades de pointes, and cardiac arrest with successful resuscitation in a patient that received lofexidine and three reports of clinically significant QT prolongation in subjects concurrently receiving methadone with lofexidine.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
Single LUCEMYRA doses of 1.44 to 1.8 mg produced maximum mean change from baseline in QTcF (ΔQTcF) of 14.4 msec (upper two-sided 90% CI: 22.3 msec) and 13.6 msec (17.4 msec) for 1.44 and 1.8 mg respectively in healthy normal volunteers.
In a Phase 3 placebo-controlled, dose response study in opioid dependent subjects, LUCEMYRA was associated with a maximum mean prolongation of the QTcF interval 7.3 (8.8) and 9.3 (10.9) msec at doses of 2.16 and 2.88 mg/day, respectively.
Patients with hepatic impairment
Administration of LUCEMYRA to subjects with hepatic impairment was associated with prolongation of the QTc interval, which was more pronounced in subjects with severe hepatic impairment [see USE IN SPECIFIC POPULATIONS (8.6)].
Patients with renal impairment
Administration of LUCEMYRA to subjects with renal impairment was associated with prolongation of the QTc interval, which was more pronounced in subjects with severe renal impairment [see USE IN SPECIFIC POPULATIONS (8.7)]
LUCEMYRA coadministered with methadone
LUCEMYRA (2.88 mg/day) coadministered with methadone in 18 methadone-maintained patients (80-120 mg/day) resulted in a maximum mean increase from methadone-alone baseline in QTcF of 9.1 (14.2) msec.
LUCEMYRA coadministered with buprenorphine
LUCEMYRA (2.88 mg/day) coadministered with buprenorphine in 21 buprenorphine-maintained patients (16-24 mg/day) resulted in a maximum mean QTcF increase in QTcF of 15 (5.6) msec compared to a buprenorphine-alone baseline.
PATIENT PACKAGE INSERT
Before taking LUCEMYRA, tell your healthcare provider about all of your medical conditions, including if you:
have low blood pressure
have a slow heart rate
have any heart problems, including history of heart attack or a condition called long QT syndrome
have liver or kidney problems
drink alcohol
are pregnant or plan to become pregnant. It is not known if LUCEMYRA can harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if LUCEMYRA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with LUCEMYRA.
USE IN SPECIFIC POPULATIONS
Hepatic Impairment
Clinically relevant QT prolongation may occur in subjects with hepatic impairment [see WARNINGS AND PRECAUTIONS (5.2), CLINICAL PHARMACOLOGY (12.2)].
[Renal Impairment]
Clinically relevant QT prolongation may occur in subjects with renal impairment [see WARNINGS AND PRECAUTIONS (5.2), CLINICAL PHARMACOLOGY (12.2)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24092

Other ADRs

355

38381232

Odds Ratio = 0.0

Drug Property Information

ATC Code(s):

N07BC04 - lofexidine hydrochloride

N07BC - Drugs used in opioid dependence
N07B - DRUGS USED IN ADDICTIVE DISORDERS
N07 - OTHER NERVOUS SYSTEM DRUGS
N - NERVOUS SYSTEM

Active Ingredient:LOFEXIDINE HYDROCHLORIDE

Active Ingredient UNII:V47G1SDI1B

Drugbank ID:DB04948

PubChem Compound:30668

CTD ID:C025655

PharmGKB:PA164744510

CAS Number:31036-80-3

Dosage Form(s):tablet, film coated

Route(s) Of Administrator:oral

Daily Dose:

1.4 mg/day N07BC04

Chemical Structure:

SMILE Code:
CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1

Reference

N/A