DIQTA 1.0: Drug-Induced QT Prolongation Atlas

APREPITANT

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 AND PRECAUTIONS
Clinically Significant CYP3A4 Drug Interactions
Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4.
Use of aprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug.
Use of pimozide with aprepitant is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide [see Contraindications (4)].
CONTRAINDICATIONS
Aprepitant is contraindicated in patients:
taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of this drug which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1)].
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
In a randomized, double-blind, positive-controlled, thorough QTc study, a single 200-mg dose of fosaprepitant had no effect on the QTc interval. Maximum aprepitant concentrations after a single 200-mg dose of fosaprepitant were 4- and 9-fold higher than that achieved with oral aprepitant 125 mg and 40 mg, respectively. QT prolongation with the oral aprepitant dosing regimens is not expected.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24089

Other ADRs

7437

38374150

Odds Ratio = 0.643

Drug Property Information

ATC Code(s):

A04AD12 - aprepitant

A04AD - Other antiemetics
A04A - ANTIEMETICS AND ANTINAUSEANTS
A04 - ANTIEMETICS AND ANTINAUSEANTS
A - ALIMENTARY TRACT AND METABOLISM

Active Ingredient:APREPITANT

Active Ingredient UNII:1NF15YR6UY

Drugbank ID:DB00673

PubChem Compound:6918365

CTD ID:D000077608

PharmGKB:PA164747039

CAS Number:170729-80-3

Dosage Form(s):capsule; kit

Route(s) Of Administrator:oral

Daily Dose:

165.0 mg/day A04AD12

Chemical Structure:

SMILE Code:
C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F

Reference

1: Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.

[Weibel Stephanie,Rücker Gerta,Eberhart Leopold Hj,Pace Nathan L,Hartl Hannah M,Jordan Olivia L,Mayer Debora,Riemer Manuel,Schaefer Maximilian S,Raj Diana,Backhaus Insa,Helf Antonia,Schlesinger Tobias,Kienbaum Peter,Kranke Peter]
Cochrane Database Syst Rev,2020 Oct 19;10:CD012859. PMID: 33075160

2: Safety of an Oral Fixed Combination of Netupitant and Palonosetron (NEPA): Pooled Data From the Phase II/III Clinical Program.

[Aapro Matti,Hesketh Paul J,Jordan Karin,Gralla Richard J,Rossi Giorgia,Rizzi Giada,Palmas Marco]
Oncologist,2016 Apr;21(4):494-502. PMID: 27000465

3: Lack of effect of aprepitant or its prodrug fosaprepitant on QTc intervals in healthy subjects.

[Marbury Thomas C,Jin Bo,Panebianco Deborah,Murphy M Gail,Sun Hong,Evans Judith K,Han Tae H,Constanzer Marvin L,Dru James,Shadle Craig R]
Anesth Analg,2009 Aug;109(2):418-25. PMID: 19608812

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