DIQTA 1.0: Drug-Induced QT Prolongation Atlas

FOSAPREPITANT

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
Fosaprepitant, a prodrug of aprepitant, is a weak inhibitor of CYP3A4, and aprepitant is a substrate, inhibitor, and inducer of CYP3A4.
Use of fosaprepitant with other drugs that are CYP3A4 substrates, may result in increased plasma concentration of the concomitant drug.
Use of pimozide with fosaprepitant 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
Fosaprepitant is contraindicated in patients:
taking pimozide. Inhibition of CYP3A4 by aprepitant, the active moiety, 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 (approximately 1.3 times the recommended dose) had no effect on the QTC interval.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24091

Other ADRs

3073

38378514

Odds Ratio = 0.519

Drug Property Information

ATC Code(s):

Active Ingredient:FOSAPREPITANT DIMEGLUMINE

Active Ingredient UNII:D35FM8T64X

Drugbank ID:DB00673

PubChem Compound:6918365

CTD ID:C579707

PharmGKB:PA164747039

CAS Number:170729-80-3

Dosage Form(s):injection, powder, lyophilized, for solution

Route(s) Of Administrator:intravenous

Daily Dose:

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: 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

Search for drugs: