DIQTA 1.0: Drug-Induced QT Prolongation Atlas

RILPIVIRINE 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 Adverse Reactions or Loss of Virologic Response Due to Drug Interactions
The concomitant use of EDURANT and other drugs may result in potentially significant drug interactions, some of which may lead to [see DOSAGE AND ADMINISTRATION (2.2), CONTRAINDICATIONS (4), and DRUG INTERACTIONS (7)]:
Loss of therapeutic effect of EDURANT and possible development of resistance.
In healthy subjects, 75 mg once daily and 300 mg once daily (3 times and 12 times the dose in EDURANT) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to EDURANT when coadministered with a drug that is known to have a risk of torsade de pointes [see DRUG INTERACTIONS (7) and CLINICAL PHARMACOLOGY (12.2)].
See TABLE 5 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during EDURANT therapy and review concomitant medications during EDURANT therapy.
DRUG INTERACTIONS
QT Prolonging Drugs
There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In a study of healthy subjects, 75 mg once daily and 300 mg once daily (3 times and 12 times the dose in EDURANT) have been shown to prolong the QTc interval of the electrocardiogram [see CLINICAL PHARMACOLOGY (12.2)]. Consider alternatives to EDURANT when coadministered with a drug with a known risk of torsade de pointes.
OVERDOSAGE
There is no specific antidote for overdose with EDURANT. Human experience of overdose with EDURANT is limited. Treatment of overdose with EDURANT consists of general supportive measures including monitoring of vital signs and ECG (QT interval) as well as observation of the clinical status of the patient. It is advisable to contact a poison control center to obtain the latest recommendations for the management of an overdose. Since rilpivirine is highly bound to plasma protein, dialysis is unlikely to result in significant removal of the active substance.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Effects on Electrocardiogram
The effect of EDURANT at the recommended dose of 25 mg once daily on the QTcF interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg once daily) controlled crossover study in 60 healthy adults, with 13 measurements over 24 hours at steady state. The maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline-correction was 2.0 (5.0) milliseconds (i.e., below the threshold of clinical concern).
When doses of 75 mg once daily and 300 mg once daily of EDURANT (3 times and 12 times the dose in EDURANT) were studied in healthy adults, the maximum mean time-matched (95% upper confidence bound) differences in QTcF interval from placebo after baseline-correction were 10.7 (15.3) and 23.3 (28.4) milliseconds, respectively. Steady-state administration of EDURANT 75 mg once daily and 300 mg once daily resulted in a mean steady-state Cmax approximately 2.6-fold and 6.7-fold, respectively, higher than the mean Cmax observed with the recommended 25 mg once daily dose of EDURANT [see WARNINGS AND PRECAUTIONS (5.4)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24082

Other ADRs

2014

38379573

Odds Ratio = 7.914

Drug Property Information

ATC Code(s):

J05AG05 - rilpivirine hydrochloride

J05AG - Non-nucleoside reverse transcriptase inhibitors
J05A - DIRECT ACTING ANTIVIRALS
J05 - ANTIVIRALS FOR SYSTEMIC USE
J - ANTIINFECTIVES FOR SYSTEMIC USE

Active Ingredient:rilpivirine hydrochloride

Active Ingredient UNII:212WAX8KDD

Drugbank ID:DB08864

PubChem Compound:6451164

CTD ID:D000068696

PharmGKB:

CAS Number:500287-72-9

Dosage Form(s):tablet, film coated

Route(s) Of Administrator:oral

Daily Dose:

25.0 mg/day J05AG05

Chemical Structure:

SMILE Code:
CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC2=CC=C(C=C2)C#N)=N1

Reference

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