DIQTA 1.0: Drug-Induced QT Prolongation Atlas

ROMIDEPSIN

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Ambiguous

Severity Score:1.0

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

WARNINGS AND PRECAUTIONS
Electrocardiographic Changes
Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [see Adverse Reactions (6.1)].
In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, consider cardiovascular monitoring of ECGs at baseline and periodically during treatment.
Confirm that potassium and magnesium levels are within normal range before administration of Romidepsin Injection [see Adverse Reactions (6.1)].
ADVERSE REACTIONS
Clinical Trials Experience
Discontinuations
Discontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Discontinuations occurring in at least 2% of patients in either study included infection, fatigue, dyspnea, QT prolongation, and hypomagnesemia.
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
At doses of 14 mg/m2 as a 4-hour intravenous infusion and at doses of 8 (0.57 times the recommended dose), 10 (0.71 times the recommended dose) or 12 (0.86 times the recommended dose) mg/m2 as a 1-hour infusion, no large changes in the mean QTc interval (>20 milliseconds) from baseline based on Fridericia correction method were detected. Small increase in mean QT interval (< 10 milliseconds) and mean QT interval increase between 10 to 20 milliseconds cannot be excluded.
Romidepsin was associated with a delayed concentration-dependent increase in heart rate in patients with advanced cancer with a maximum mean increase in heart rate of 20 beats per minute occurring at the 6-hour time point after start of romidepsin infusion for patients receiving 14 mg/m2 as a 4-hour infusion.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24071

Other ADRs

2537

38379050

Odds Ratio = 13.198

Drug Property Information

ATC Code(s):

L01XH02 - romidepsin

L01XH -
L01X - OTHER ANTINEOPLASTIC AGENTS
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:ROMIDEPSIN

Active Ingredient UNII:CX3T89XQBK

Drugbank ID:DB06176

PubChem Compound:57515973

CTD ID: C087123

PharmGKB:PA166161306

CAS Number:128517-07-7

Dosage Form(s):injection, solution, concentrate

Route(s) Of Administrator:intravenous

Daily Dose:

Chemical Structure:

SMILE Code:
C\C=C1/NC(=O)[C@H]2CSSCC\C=C\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C

Reference

1: Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial.

[Leth Steffen,Schleimann Mariane H,Nissen Sara K,Højen Jesper F,Olesen Rikke,Graversen Mette E,Jørgensen Sofie,Kjær Anne Sofie,Denton Paul W,Mørk Alejandra,Sommerfelt Maja A,Krogsgaard Kim,Østergaard Lars,Rasmussen Thomas A,Tolstrup Martin,Søgaard Ole Schmeltz]
Lancet HIV,2016 Oct;3(10):e463-72. PMID: 27658863

2: Romidepsin for the Treatment of Peripheral T-Cell Lymphoma.

[Iyer Swaminathan P,Foss Francine F]
Oncologist,2015 Sep;20(9):1084-91. PMID: 26099743

3: Impact of ABCB1 allelic variants on QTc interval prolongation.

[Sissung Tristan M,Gardner Erin R,Piekarz Richard L,Howden Reuben,Chen Xiaohong,Woo Sukyung,Franke Ryan,Clark James A,Miller-DeGraff Laura,Steinberg Seth M,Venzon David,Liewehr David,Kleeberger Steven R,Bates Susan E,Price Douglas K,Rosing Douglas R,Cabell Christopher,Sparreboom Alex,Figg William D]
Clin Cancer Res,2011 Feb 15;17(4):937-46. PMID: 21106724

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