DIQTA 1.0: Drug-Induced QT Prolongation Atlas

FOSTEMSAVIR TROMETHAMINE

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
QTc Prolongation with Higher than Recommended Dosages
RUKOBIA at 2,400 mg twice daily, 4 times the recommended daily dose, has been shown to significantly prolong the QTc interval of the electrocardiogram [see Drug Interactions (7.4), Clinical Pharmacology (12.2)]. RUKOBIA should be used with caution in patients with a history of QTc interval prolongation, when coadministered with a drug with a known risk of Torsade de Pointes, or in patients with relevant pre-existing cardiac disease. Elderly patients may be more susceptible to drug-induced QT interval prolongation.
DRUG INTERACTIONS
Drugs that Prolong QT Interval
Coadministration of RUKOBIA with a drug with a known risk of Torsade de Pointes may increase the risk of Torsade de Pointes [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2)]. Use RUKOBIA with caution when coadministered with drugs with a known risk of Torsade de Pointes.
OVERDOSAGE
There is no known specific treatment for overdose with RUKOBIA. If overdose occurs, the patient should be monitored and standard supportive treatment applied as required, including monitoring of vital signs and ECG (QT interval), as well as observation of the clinical status of the patient. As fostemsavir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
ADVERSE REACTIONS
Cardiac Disorders: Electrocardiogram QT prolonged. All reports were asymptomatic.
[Drugs that Prolong QT Interval]
Coadministration of RUKOBIA with a drug with a known risk of Torsade de Pointes may increase the risk of Torsade de Pointes [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2)]. Use RUKOBIA with caution when coadministered with drugs with a known risk of Torsade de Pointes.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
At therapeutic doses, RUKOBIA does not prolong the QT interval to any clinically relevant extent. At 4 times the recommended dose, the mean (upper 90% confidence interval) QTcF increase was 11.2 milliseconds (13.3 milliseconds). The observed increase in QTcF was temsavir concentration-dependent [see Warnings and Precautions (5.2)].
PATIENT COUNSELING INFORMATION
QTc Interval Prolongation
Advise patients that RUKOBIA may produce changes in their electrocardiogram (i.e., QT prolongation). Instruct patients to consult their healthcare provider if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness [see Warnings and Precautions (5.2)].
PATIENT PACKAGE INSERT
RUKOBIA can cause serious side effects including:
Heart rhythm problems (QTc prolongation). RUKOBIA may cause a heart rhythm problem called QTc prolongation. QTc prolongation causes an irregular heartbeat. If you are elderly, you may be at a greater risk for developing this heart problem with RUKOBIA.
USE IN SPECIFIC POPULATIONS
Geriatric Use
Clinical trials of RUKOBIA did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. In general, caution should be exercised in administration of RUKOBIA in elderly patients reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)]. Elderly patients may be more susceptible to drug-induced QT interval prolongation [see Warnings and Precautions (5.2)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24092

Other ADRs

38381587

Odds Ratio = N/A

Drug Property Information

ATC Code(s):

J05AX29 - fostemsavir tromethamine

J05AX2 -
J05AX - Other antivirals
J05A - DIRECT ACTING ANTIVIRALS
J05 - ANTIVIRALS FOR SYSTEMIC USE
J - ANTIINFECTIVES FOR SYSTEMIC USE

Active Ingredient:FOSTEMSAVIR TROMETHAMINE

Active Ingredient UNII:2X513P36U0

Drugbank ID:DB11796

PubChem Compound:11319217

CTD ID:C576364

PharmGKB:

CAS Number:864953-29-7

Dosage Form(s):tablet, film coated, extended release

Route(s) Of Administrator:oral

Daily Dose:

Chemical Structure:

SMILE Code:
COC1=C2C(=CN(COP(O)(O)=O)C2=C(N=C1)N1C=NC(C)=N1)C(=O)C(=O)N1CCN(CC1)C(=O)C1=CC=CC=C1

Reference

N/A