DIQTA 1.0: Drug-Induced QT Prolongation Atlas

INOTUZUMAB OZOGAMICIN

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
QT Interval Prolongation
In the INO-VATE ALL trial, increases in QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ to 60 msec from baseline were measured in 4/162 patients (3%). No patients had QTcF values greater than 500 msec [see CLINICAL PHARMACOLOGY (12.2)]. Grade 2 QT prolongation was reported in 2/164 patients (1%). No ≥ Grade 3 QT prolongation or events of Torsade de Pointes were reported [see ADVERSE REACTIONS (6.1)].
Administer BESPONSA with caution in patients who have a history of or predisposition for QTc prolongation, who are taking medicinal products that are known to prolong QT interval [see DRUG INTERACTIONS (7)], and in patients with electrolyte disturbances [see DRUG INTERACTIONS (7)]. Obtain electrocardiograms (ECGs) and electrolytes prior to the start of treatment, after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment [see DRUG INTERACTIONS (7), CLINICAL PHARMACOLOGY (12.2)]).
DRUG INTERACTIONS
Drugs That Prolong the QT Interval
Concomitant use of BESPONSA with drugs known to prolong the QT interval or induce Torsades de Pointes may increase the risk of a clinically significant QTc interval prolongation [see CLINICAL PHARMACOLOGY (12.2)]. Discontinue or use alternative concomitant drugs that do not prolong QT/QTc interval while the patient is using BESPONSA. When it is not feasible to avoid concomitant use of drugs known to prolong QT/QTc, obtain ECGs and electrolytes prior to the start of treatment, after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment [see WARNINGS AND PRECAUTIONS (5.5)].
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
Hepatotoxicity, including hepatic VOD (also known as SOS) [see WARNINGS AND PRECAUTIONS (5.1)]
Increased risk of post-transplant non-relapse mortality [see WARNINGS AND PRECAUTIONS (5.2)]
Myelosuppression [see WARNINGS AND PRECAUTIONS (5.3)]
Infusion related reactions [see WARNINGS AND PRECAUTIONS (5.4)]
QT interval prolongation [see WARNINGS AND PRECAUTIONS (5.5)]
[Clinical Trials Experience]
Additional adverse reactions (all grades) that were reported in less than 10% of patients treated with BESPONSA included: lipase increased (9%), abdominal distension (6%), amylase increased (5%), hyperuricemia (4%), ascites (4%), infusion related reaction (2%; includes the following: hypersensitivity and infusion related reaction), pancytopenia (2%; includes the following: bone marrow failure, febrile bone marrow aplasia, and pancytopenia), tumor lysis syndrome (2%), and electrocardiogram QT prolonged (1%).
CLINICAL PHARMACOLOGY
Cardiac Electrophysiology
In a randomized clinical study in patients with relapsed or refractory ALL, increases in QTcF of ≥ 60 msec from baseline were measured in 4/162 patients (3%) in the BESPONSA arm and 3/124 patients (2%) in the Investigator's choice of chemotherapy arm. Increases in QTcF of > 500 msec were observed in none of the patients in the BESPONSA arm and 1/124 patients (1%) in the Investigator's choice of chemotherapy arm. Central tendency analysis of the QTcF interval changes from baseline showed that the highest mean (upper bound of the 2-sided 90% CI) for QTcF was 15.3 (21.1) msec, which was observed at Cycle 4/Day 1/1 hour in the BESPONSA arm [see WARNINGS AND PRECAUTIONS (5.5)].
PATIENT COUNSELING INFORMATION
QT Interval Prolongation
Inform patients of symptoms that may be indicative of significant QTc prolongation including dizziness, lightheadedness, and syncope. Advise patients to report these symptoms and the use of all medications to their healthcare provider [see WARNINGS AND PRECAUTIONS (5.5)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24092

Other ADRs

1451

38380136

Odds Ratio = 0.0

Drug Property Information

ATC Code(s):

L01XC26 - inotuzumab ozogamicin

L01XC - Monoclonal antibodies
L01X - OTHER ANTINEOPLASTIC AGENTS
L01 - ANTINEOPLASTIC AGENTS
L - ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Active Ingredient:INOTUZUMAB OZOGAMICIN

Active Ingredient UNII:P93RUU11P7

Drugbank ID:DB05889

PubChem Compound:N/ADIR Classification

CTD ID:D000080045

PharmGKB:

CAS Number:

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

Route(s) Of Administrator:intravenous

Daily Dose:

Chemical Structure:

SMILE Code:

Reference

1: Effect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc-concentration modelling.

[Hibma Jennifer E,Kantarjian Hagop M,DeAngelo Daniel J,Boni Joseph P]
Br J Clin Pharmacol,2019 Mar;85(3):590-600. PMID: 30536405

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