DIQTA 1.0: Drug-Induced QT Prolongation Atlas

OLICERIDINE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIQT concern

Severity Score:2.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

WARNINGS AND PRECAUTIONS
Potential for QT prolongation with Daily Doses exceeding 27 mg
The effect of oliceridine on cardiac physiology was studied in single and multiple-dose thorough QT studies. The multiple-dose study was conducted with a maximum daily cumulative dose of 27 mg. In both studies, there was mild QTc interval prolongation. In the multiple-dose study, the maximum mean ΔΔQTcI was 11.7 ms (two-sided 90% UCI 14.7 ms) at 9 hours. The effect on QT prolongation at total cumulative daily doses >27 mg has not been studied in a thorough QT study [see Clinical Pharmacology (12.2)]. Total cumulative daily doses exceeding 27 mg per day may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg [see Dosage and Administration (2.2)].
ADVERSE REACTIONS
Clinical Studies Experience
The most common adverse drug reactions (≥10%) in controlled efficacy trials (Study 1 and Study 2) were nausea, vomiting, dizziness, headache, constipation, pruritus and hypoxia. Adverse reactions leading to discontinuation of OLINVYK were hypotension, hypoxia, nausea, hypoventilation, oxygen saturation decreased, alanine aminotransferase increased, aspartate aminotransferase increased, electrocardiogram QT prolongation, and urticaria. In two randomized, double-blind, placebo- and morphine-controlled studies, when stratified by 27 mg daily dosing limit, discontinuation of OLINVYK due to adverse reactions occurred in 4% of patients who received a daily dose ≤ 27 mg, and less than 1% of patients who received a daily dose >27 mg. In these same studies, discontinuation due to adverse reactions occurred in 5% of morphine-treated patients, and no placebo-treated patients. In an open-label safety study, discontinuation of OLINVYK due to adverse drug reactions occurred in 3% of patients who received a daily dose ≤ 27 mg, and 1% of patients who received a daily dose >27 mg.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of oliceridine on the QTc interval was evaluated in 2 dedicated Thorough QT/QTc studies. A single-dose, randomized, positive- (moxifloxacin) and placebo-controlled 4 period crossover study evaluated the ECG effects of oliceridine at a therapeutic (3 mg IV infusion) and a supratherapeutic (6 mg IV infusion) dose in 62 healthy volunteers. Dose-dependent QTc prolongation (3 mg: 7 ms [upper 90% CI: 9 ms]; 6 mg: 12 ms [14 ms]), which occurred after peak oliceridine plasma concentration, was observed in this study.
A multi-dose, randomized, positive- (moxifloxacin) and placebo-controlled 3-way crossover study in 65 healthy volunteers evaluated intermittent dosing over 24 hours to the maximum daily cumulative dose of 27 mg. The maximum mean ΔΔQTcI was 11.7 ms (two-sided 90% UCI 14.7 ms) at 9 hours. Thereafter, the QTc effect did not progressively increase with repeat dosing, and despite continued dosing began to diminish after 12 hours.
The underlying mechanism and clinical significance of the transient QT changes seen in the single-dose and multiple-dose studies in healthy volunteers are unknown. These findings should be carefully considered when OLINVYK is administered in clinical settings where prolongation of the QT interval has been observed either due to the use of concomitant medications known to prolong the QT interval or to underlying medical conditions associated with QT interval prolongation.
INDICATIONS AND USAGE
The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation. [see Warnings and Precautions (5.5].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24092

Other ADRs

38381587

Odds Ratio = N/A

Drug Property Information

ATC Code(s):

Active Ingredient:OLICERIDINE

Active Ingredient UNII:MCN858TCP0

Drugbank ID:DB14881

PubChem Compound:N/ADIR Classification

CTD ID:C586842

PharmGKB:

CAS Number:1401028-24-7

Dosage Form(s):injection, solution

Route(s) Of Administrator:intravenous

Daily Dose:

Chemical Structure:

SMILE Code:
COC1=C(CNCC[C@]2(CCOC3(CCCC3)C2)C2=NC=CC=C2)SC=C1

Reference

N/A