DIQTA 1.0: Drug-Induced QT Prolongation Atlas

SELPERCATINIB

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
RETEVMO can cause concentration-dependent QT interval prolongation [see Clinical Pharmacology (12.2)]. An increase in QTcF interval to >500 ms was measured in 6% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 15% of patients [see Adverse Reactions (6.1)]. RETEVMO has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction.
Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes and TSH at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia and hypocalcemia prior to initiating RETEVMO and during treatment.
Monitor the QT interval more frequently when RETEVMO is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue RETEVMO based on the severity [see Dosage and Administration (2.5)].
DRUG INTERACTIONS
Effects of Other Drugs on RETEVMO
Strong and Moderate CYP3A Inhibitors
Concomitant use of RETEVMO with a strong or moderate CYP3A inhibitor increases selpercatinib plasma concentrations [see Clinical Pharmacology (12.3)], which may increase the risk of RETEVMO adverse reactions, including QTc interval prolongation.
Avoid concomitant use of strong and moderate CYP3A inhibitors with RETEVMO. If concomitant use of strong and moderate CYP3A inhibitors cannot be avoided, reduce the RETEVMO dosage and monitor the QT interval with ECGs more frequently [see Dosage and Administration (2.6), Warning and Precautions (5.3)].
DOSAGE AND ADMINISTRATION
ADVERSE REACTIONS
Clinical Trials Experience
Dosage interruptions due to an adverse reaction occurred in 42% of patients who received RETEVMO. Adverse reactions requiring dosage interruption in ≥ 2% of patients included ALT increased, AST increased, hypertension, diarrhea, pyrexia, and QT prolongation.
Dose reductions due to an adverse reaction occurred in 31% of patients who received RETEVMO. Adverse reactions requiring dosage reductions in ≥ 2% of patients included ALT increased, AST increased, QT prolongation and fatigue.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
The effect of RETEVMO on the QTc interval was evaluated in a thorough QT study in healthy subjects. The largest mean increase in QTc is predicted to be 10.6 msec (upper 90% confidence interval: 12.1 msec) at the mean steady-state maximum concentration (Cmax) observed in patients after administration of 160 mg twice daily. The increase in QTc was concentration-dependent.
PATIENT COUNSELING INFORMATION
QT Prolongation
Advise patients that RETEVMO can cause QTc interval prolongation and to inform their healthcare provider if they have any QTc interval prolongation symptoms, such as syncope [see Warnings and Precautions (5.3)].
What are the possible side effects of RETEVMO?
RETEVMO may cause serious side effects, including:
Heart rhythm changes (QT prolongation) can occur and may be serious. RETEVMO may cause very slow, very fast or irregular heartbeats. Tell your healthcare provider right away if you get any of the following symptoms:
loss of consciousness
fainting
dizziness
a change in the way your heart beats (heart palpitations)

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:selpercatinib

Active Ingredient UNII:CEGM9YBNGD

Drugbank ID:DB15685

PubChem Compound:N/ADIR Classification

CTD ID:C000656166

PharmGKB:

CAS Number:2152628-33-4

Dosage Form(s):capsule

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
COC1=NC=C(CN2C3CC2CN(C3)C2=CC=C(C=N2)C2=CC(OCC(C)(C)O)=CN3N=CC(C#N)=C23)C=C1

Reference

N/A