inotuzumab ozogamicin

Antineoplastic Monoclonal Antibodies Targeting CD22
Antineoplastic Monoclonal Antibody-Drug Conjugates (ADCs)

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 1
Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Low
Administer routine antiemetic prophylaxis prior to treatment.

neutropenia / Delayed / 48.0-48.0
thrombocytopenia / Delayed / 42.0-42.0
leukopenia / Delayed / 33.0-33.0
infection / Delayed / 28.0-28.0
anemia / Delayed / 24.0-24.0
veno-occlusive disease (VOD) / Delayed / 0-23.0
sinusoidal obstruction syndrome (SOS) / Delayed / 0-23.0
lymphopenia / Delayed / 16.0-16.0
elevated hepatic enzymes / Delayed / 7.0-7.0
hyperbilirubinemia / Delayed / 5.0-5.0
intracranial bleeding / Delayed / 0-5.0
ecchymosis / Delayed / 0-5.0
hematoma / Early / 0-5.0
GI bleeding / Delayed / 0-5.0
bleeding / Early / 5.0-5.0
hematuria / Delayed / 0-5.0
hematemesis / Delayed / 0-5.0
subdural hematoma / Early / 0-5.0
vaginal bleeding / Delayed / 0-5.0
petechiae / Delayed / 0-5.0
hemorrhoids / Delayed / 0-5.0
fatigue / Early / 5.0-5.0
asthenia / Delayed / 5.0-5.0
abdominal pain / Early / 3.0-3.0
fever / Early / 3.0-3.0
pancytopenia / Delayed / 2.0-2.0
nausea / Early / 2.0-2.0
oral ulceration / Delayed / 0-2.0
stomatitis / Delayed / 2.0-2.0
migraine / Early / 0-2.0
headache / Early / 2.0-2.0
tumor lysis syndrome (TLS) / Delayed / 2.0-2.0
anorexia / Delayed / 1.0-1.0
diarrhea / Early / 1.0-1.0
vomiting / Early / 1.0-1.0
hepatotoxicity / Delayed / Incidence not known

constipation / Delayed / 16.0-16.0
hyperamylasemia / Delayed / 5.0-5.0
ascites / Delayed / 4.0-4.0
hyperuricemia / Delayed / 4.0-4.0
QT prolongation / Rapid / 1.0-3.0
antibody formation / Delayed / 3.0-3.0
infusion-related reactions / Rapid / 2.0-2.0
hepatomegaly / Delayed / Incidence not known

epistaxis / Delayed / 15.0-15.0
chills / Rapid / 11.0-11.0
weight gain / Delayed / Incidence not known
rash / Early / Incidence not known

Severe or life-threatening hepatotoxicity including veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) has been reported with inotuzumab ozogamicin therapy. Monitor liver function tests (LFTs) including total bilirubin and alkaline phosphatase levels prior to and following each inotuzumab ozogamicin dose. Therapy interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop liver function test abnormalities. Closely monitor patients for signs and symptoms of VOD/SOS including hepatomegaly, rapid weight gain, and ascites. Permanently discontinue therapy in patients who develop VOD/SOS; treat according to standard medical practice. In patients who undergo a hematopoietic stem-cell transplant (HSCT), monitor LFTs frequently during the first month post-HSCT; thereafter, continue to monitor LFTs but less often. The median time from HSCT to onset of VOD/SOS was 15 days (range, 3 to 57 days). The risk of VOD/SOS may be greater in patients who receive a HSCT or a conditioning regimen that contains 2 alkylating agents prior to HSCT and in patients who have an increased total bilirubin level prior to a HSCT; other risk factors include hepatic disease (e.g., cirrhosis, nodular regenerative hyperplasia, active hepatitis), a prior HSCT, increased age, later salvage lines, and a greater number of inotuzumab ozogamicin treatment cycles.

Patients who underwent a hematopoietic stem-cell transplant (HSCT) had a higher 100-day post-HSCT nonrelapse mortality rate following inotuzumab ozogamicin therapy compared with an investigator choice regimen (39% vs. 23%) in a randomized trial. Monitor patients closely for post-HSCT toxicity. The most common causes of post-HSCT death were veno-occlusive disease/sinusoidal obstruction syndrome and infectious complications.

BESPONSA

Rx

A CD22-directed antibody-drug conjugate
Used for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia
Severe or life-threatening hepatotoxicity including veno-occlusive disease/sinusoidal obstruction syndrome has been reported

Baseline Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Treatment-Related Hepatotoxicity
Evaluate patients for toxicity prior to each dose. Dosing interruptions within a cycle are recommended for hepatic impairment. If a dose reduction is necessary, do not re-escalate the dose.
Total bilirubin level of 1.5-times the upper limit of normal (ULN) or less and AST/ALT level of 2.5-times the ULN or less: no dose adjustment is necessary.
Total bilirubin level greater than 1.5-times the ULN and AST/ALT level greater than 2.5-times the ULN: hold therapy until the total bilirubin level is 1.5-times the ULN or less and the AST/ALT level is 2.5-times the ULN or less unless hyperbilirubinemia is due to Gilbert’s syndrome or hemolysis. Dose modifications depend on duration of dosing interruption as follows:
Less than 7 days (within a cycle): hold the next dose; maintain a minimum of 6 days between doses.
7 days or greater: omit the next dose within the cycle.
14 days or greater: after recovery, decrease the total dose by 25% for the subsequent cycle. If further dose modification is required, reduce the number of doses to 2 per cycle for subsequent cycles. If a 25% decrease in the total dose followed by a decrease to 2 doses per cycle is not tolerated, permanently discontinue therapy.
Greater than 28 days: permanently discontinue therapy.
Hepatic Veno-Occlusive Disease (VOD)/Sinusoidal obstruction syndrome (SOS) or Other Severe Liver Toxicity
Permanently discontinue therapy.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Adagrasib: (Major) Concomitant use of adagrasib and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Major) Avoid coadministration of inotuzumab ozogamicin with alfuzosin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) Avoid coadministration of inotuzumab ozogamicin with amiodarone due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Avoid coadministration of inotuzumab with amisulpride due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and prior to the start of treatment and periodically during treatment. Amisulpride causes dose- and concentration- dependent QT prolongation. Inotuzumab has been associated with QT interval prolongation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of inotuzumab ozogamicin with clarithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Avoid coadministration of inotuzumab ozogamicin with anagrelide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Additionally, monitor patients for cardiovascular effects during concomitant therapy and evaluate as necessary. Inotuzumab has been associated with QT interval prolongation. TdP and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects taking anagrelide.
Apomorphine: (Major) Avoid coadministration of inotuzumab ozogamicin with apomorphine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Avoid coadministration of inotuzumab ozogamicin with aripiprazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
Arsenic Trioxide: (Major) Avoid coadministration of inotuzumab ozogamicin with arsenic trioxide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Artemether; Lumefantrine: (Major) Avoid coadministration of inotuzumab ozogamicin with artemether; lumefantrine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Artemether; lumefantrine is also associated with QT interval prolongation.
Asenapine: (Major) Avoid coadministration of inotuzumab ozogamicin with asenapine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and asenapine have been associated with QT prolongation.
Atomoxetine: (Major) Avoid coadministration of inotuzumab ozogamicin with atomoxetine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
Azithromycin: (Major) Avoid coadministration of inotuzumab ozogamicin with azithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Avoid any non-essential QT prolonging drugs and correct electrolyte imbalances. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been spontaneously reported during azithromycin postmarketing surveillance.
Bedaquiline: (Major) Avoid coadministration of inotuzumab ozogamicin with bedaquiline due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during therapy (at least 2, 12, and 24 weeks after starting bedaquiline therapy). Inotuzumab has been associated with QT interval prolongation. Bedaquiline has also been reported to prolong the QT interval.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine: (Major) Avoid coadministration of inotuzumab ozogamicin with buprenorphine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
Buprenorphine; Naloxone: (Major) Avoid coadministration of inotuzumab ozogamicin with buprenorphine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
Cabotegravir; Rilpivirine: (Major) Avoid coadministration of inotuzumab ozogamicin with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Ceritinib: (Major) Avoid coadministration of inotuzumab ozogamicin with ceritinib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Inotuzumab has been associated with QT interval prolongation. Concentration-dependent QT prolongation has been reported with ceritinib.
Chloroquine: (Major) Avoid coadministration of chloroquine with inotuzumab due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Inotuzumab has also been associated with QT interval prolongation.
Chlorpromazine: (Major) Avoid coadministration of inotuzumab ozogamicin with chlorpromazine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and inotuzumab ozogamicin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Coadministration of inotuzumab ozogamicin with cisapride is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride.
Citalopram: (Major) Avoid coadministration of inotuzumab ozogamicin with citalopram due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes at baseline, after treatment initiation, and periodically during therapy. Inotuzumab has been associated with QT interval prolongation. Citalopram causes dose-dependent QT interval prolongation.
Clarithromycin: (Major) Avoid coadministration of inotuzumab ozogamicin with clarithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Clofazimine: (Major) Concomitant use of clofazimine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Avoid coadministration of inotuzumab ozogamicin with clozapine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Crizotinib: (Major) Avoid coadministration of inotuzumab ozogamicin with crizotinib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Inotuzumab has been associated with QT interval prolongation. Crizotinib has also been associated with concentration-dependent QT prolongation.
Dasatinib: (Major) Avoid coadministration of inotuzumab ozogamicin with dasatinib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Major) Avoid coadministration of inotuzumab ozogamicin with degarelix due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Desflurane: (Major) Avoid coadministration of inotuzumab ozogamicin with halogenated anesthetics due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, monitor the ECG and electrolytes. Inotuzumab has been associated with QT interval prolongation. Halogenated anesthetics can also prolong the QT interval.
Deutetrabenazine: (Major) Avoid coadministration of inotuzumab with deutetrabenazine due to the potential for additive QT interval prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of inotuzumab treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and inotuzumab ozogamicin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) Avoid coadministration of inotuzumab ozogamicin with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinidine administration is also associated with QT prolongation and TdP.
Disopyramide: (Major) Avoid coadministration of inotuzumab ozogamicin with disopyramide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Disopyramide administration is associated with QT prolongation and TdP.
Dofetilide: (Major) Avoid coadministration of inotuzumab with dofetilide due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP.
Dolasetron: (Major) Avoid coadministration of inotuzumab ozogamicin with dolasetron due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an ECG.
Dolutegravir; Rilpivirine: (Major) Avoid coadministration of inotuzumab ozogamicin with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Major) Avoid coadministration of inotuzumab ozogamicin with donepezil due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
Donepezil; Memantine: (Major) Avoid coadministration of inotuzumab ozogamicin with donepezil due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP.
Dronedarone: (Contraindicated) Coadministration of inotuzumab with dronedarone is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Avoid coadministration of inotuzumab ozogamicin with droperidol due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Additionally, initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Inotuzumab has been associated with QT interval prolongation. Droperidol administration is associated with an established risk for QT prolongation and TdP. Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
Efavirenz: (Major) Avoid coadministration of inotuzumab ozogamicin with efavirenz due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of inotuzumab ozogamicin with efavirenz due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of inotuzumab ozogamicin with efavirenz due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QTc prolongation has been observed with the use of efavirenz.
Eliglustat: (Major) Avoid coadministration of inotuzumab ozogamicin with eliglustat due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of inotuzumab ozogamicin with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of inotuzumab ozogamicin with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and inotuzumab due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Inotuzumab has also been associated with QT interval prolongation.
Entrectinib: (Major) Avoid coadministration of inotuzumab with entrectinib due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Both entrectinib and inotuzumab have been associated with QT prolongation.
Eribulin: (Major) Avoid coadministration of inotuzumab ozogamicin with eribulin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment; closely monitor the patient for QT interval prolongation. Both inotuzumab and eribulin have been associated with QT prolongation.
Erythromycin: (Major) Avoid coadministration of inotuzumab ozogamicin with erythromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Erythromycin is associated with QT prolongation and TdP.
Escitalopram: (Major) Avoid coadministration of inotuzumab ozogamicin with escitalopram due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Escitalopram has been associated with a risk of QT prolongation and TdP.
Fingolimod: (Major) Avoid coadministration of inotuzumab ozogamicin with fingolimod due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Specifically, overnight monitoring with continuous ECG in a medical facility is advised after the first fingolimod dose. Inotuzumab has been associated with QT interval prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Avoid coadministration of inotuzumab ozogamicin with flecainide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Major) Avoid coadministration of inotuzumab ozogamicin with fluconazole due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Fluconazole has been associated with QT prolongation and rare cases of TdP.
Fluoxetine: (Major) Avoid coadministration of inotuzumab ozogamicin with fluoxetine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been reported in patients treated with fluoxetine.
Fluphenazine: (Minor) Coadministration of inotuzumab ozogamicin with fluphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Fluphenazine is also associated with a possible risk for QT prolongation.
Fluvoxamine: (Major) Avoid coadministration of inotuzumab ozogamicin with fluvoxamine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Inotuzumab has been associated with QT prolongation. If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment.
Foscarnet: (Major) Avoid coadministration of inotuzumab ozogamicin with foscarnet due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Both QT prolongation and TdP have been reported during postmarketing use of foscarnet.
Fostemsavir: (Major) Avoid coadministration of inotuzumab with fostemsavir due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Avoid coadministration of inotuzumab ozogamicin with gemifloxacin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Gemifloxacin may prolong the QT interval in some patients. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gilteritinib: (Major) Avoid coadministration of inotuzumab with gilteritinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and prior to the start of treatment and periodically during treatment. Both drugs have been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with inotuzumab due to the potential for additive QT prolongation. If coadministration cannot be avoided, obtain ECGs prior to the start of treatment and increase the frequency of ECG monitoring during concurrent use. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Inotuzumab has also been associated with QT interval prolongation.
Goserelin: (Major) Avoid coadministration of inotuzumab with goserelin due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of inotuzumab ozogamicin with granisetron due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes at baseline, after treatment initiation, and periodically during therapy as clinically indicated. Both inotuzumab and granisetron have been associated with QT prolongation.
Halogenated Anesthetics: (Major) Avoid coadministration of inotuzumab ozogamicin with halogenated anesthetics due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, monitor the ECG and electrolytes. Inotuzumab has been associated with QT interval prolongation. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of inotuzumab ozogamicin with haloperidol due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Avoid coadministration of inotuzumab with histrelin due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of inotuzumab and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of inotuzumab and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Avoid coadministration of inotuzumab ozogamicin with ibutilide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Avoid coadministration of inotuzumab ozogamicin with iloperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and iloperidone have been associated with QT prolongation.
Isoflurane: (Major) Avoid coadministration of inotuzumab ozogamicin with halogenated anesthetics due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, monitor the ECG and electrolytes. Inotuzumab has been associated with QT interval prolongation. Halogenated anesthetics can also prolong the QT interval.
Itraconazole: (Major) Avoid coadministration of inotuzumab ozogamicin with itraconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and itraconazole have been associated with QT prolongation.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with inotuzumab due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Inotuzumab has been associated with QT interval prolongation.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and inotuzumab due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of inotuzumab ozogamicin with clarithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Avoid coadministration of inotuzumab with lapatinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment; also monitor electrolytes. Correct any electrolyte abnormalities prior to treatment. Inotuzumab has been associated with QT interval prolongation. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib.
Lefamulin: (Major) Avoid coadministration of lefamulin with inotuzumab as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG before and during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Inotuzumab has been associated with QT interval prolongation.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with inotuzumab due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Inotuzumab has also been associated with QT interval prolongation.
Leuprolide: (Major) Avoid coadministration of inotuzumab with leuprolide due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide ) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of inotuzumab with leuprolide due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., leuprolide ) may prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of levofloxacin and inotuzumab ozogamicin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and inotuzumab due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lithium: (Major) Avoid coadministration of inotuzumab ozogamicin with lithium due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and lithium have been associated with QT interval prolongation.
Lofexidine: (Major) Avoid coadministration of lofexidine and inotuzumab due to the potential for additive QT prolongation. If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Inotuzumab has been associated with QT interval prolongation.
Loperamide: (Major) Avoid coadministration of inotuzumab ozogamicin with loperamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Loperamide; Simethicone: (Major) Avoid coadministration of inotuzumab ozogamicin with loperamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with inotuzumab due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as inotuzumab. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Inotuzumab has been associated with QT interval prolongation.
Maprotiline: (Major) Avoid coadministration of inotuzumab ozogamicin with maprotiline due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Major) Avoid coadministration of inotuzumab ozogamicin with mefloquine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Methadone: (Major) Avoid coadministration of inotuzumab ozogamicin with methadone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Metronidazole: (Major) Concomitant use of metronidazole and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Avoid coadministration of inotuzumab ozogamicin with midostaurin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and midostaurin have been associated with QT prolongation.
Mifepristone: (Major) Concomitant use of inotuzumab and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of inotuzumab and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Avoid coadministration of inotuzumab ozogamicin with moxifloxacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and moxifloxacin have been associated with QT prolongation. Although extremely rare, TdP has also been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Nilotinib: (Major) Avoid coadministration of inotuzumab ozogamicin with nilotinib due to the potential for additive QT prolongation and risk of torsade de pointes. If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment; closely monitor for evidence of QT prolongation during concurrent use. Inotuzumab has been associated with QT interval prolongation. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy.
Ofloxacin: (Major) Concomitant use of ofloxacin and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Avoid coadministration of inotuzumab ozogamicin with olanzapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of inotuzumab ozogamicin with fluoxetine due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and TdP have been reported in patients treated with fluoxetine. (Major) Avoid coadministration of inotuzumab ozogamicin with olanzapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Major) Avoid coadministration of inotuzumab ozogamicin with olanzapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Ondansetron: (Major) Concomitant use of ondansetron and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Avoid coadministration of inotuzumab with osilodrostat due to the potential for additive QT prolongation. If coadministration is unavoidable, obtain ECGs and prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of inotuzumab with osimertinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and prior to the start of treatment and periodically during treatment; monitor electrolytes. An interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Inotuzumab has been associated with QT interval prolongation, and concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Oxaliplatin: (Major) Avoid coadministration of inotuzumab ozogamicin with oxaliplatin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Correct electrolyte abnormalities prior to treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation and ventricular arrhythmias including, fatal TdP, have been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) Avoid coadministration of inotuzumab with ozanimod due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Pacritinib: (Major) Concomitant use of pacritinib and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Avoid coadministration of inotuzumab ozogamicin with paliperidone if possible due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Both inotuzumab and paliperidone have been associated with QT interval prolongation; TdP and ventricular fibrillation have been reported in the setting of paliperidone overdose. If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Close monitoring is essential for patients with known risk factors for cardiac disease or arrhythmias.
Panobinostat: (Major) Avoid coadministration of inotuzumab ozogamicin with panobinostat due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and panobinostat have been associated with QT interval prolongation.
Pasireotide: (Major) Avoid coadministration of inotuzumab ozogamicin with pasireotide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Avoid coadministration of inotuzumab ozogamicin with pazopanib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and pazopanib have been associated with QT interval prolongation.
Pentamidine: (Major) Avoid coadministration of inotuzumab ozogamicin with pentamidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Systemic pentamidine has also been associated with QT prolongation.
Perphenazine: (Minor) Coadministration of inotuzumab ozogamicin with perphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Perphenazine is also associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Coadministration of inotuzumab ozogamicin with perphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Perphenazine is also associated with a possible risk for QT prolongation.
Pimavanserin: (Major) Avoid coadministration of inotuzumab ozogamicin with pimavanserin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Pimavanserin may also cause QT prolongation.
Pimozide: (Contraindicated) Coad ministration of inotuzumab ozogamicin with pimozide is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Inotuzumab has also been associated with QT interval prolongation.
Pitolisant: (Major) Avoid coadministration of inotuzumab with pitolisant due to the potential for additive QT prolongation and torsade de pointes. If coadministration cannot be avoided, monitor ECG before and during treatment. Inotuzumab has been associated with QT interval prolongation. Pitolisant also prolongs the QT interval.
Ponesimod: (Major) Avoid coadministration of inotuzumab and ponesimod due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment and monitor for signs and symptoms of infection. Inotuzumab has been associated with QT interval prolongation. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Posaconazole: (Major) Avoid coadministration of inotuzumab ozogamicin with posaconazole in due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Posaconazole has also been associated with QT interval prolongation as well as rare cases of TdP.
Primaquine: (Major) Avoid coadministration of inotuzumab ozogamicin with primaquine in due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and primaquine have been associated with QT interval prolongation.
Procainamide: (Major) Avoid coadministration of inotuzumab ozogamicin with procainamide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) Coadministration of inotuzumab ozogamicin with prochlorperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Prochlorperazine is also associated with a possible risk for QT prolongation.
Promethazine: (Major) Concomitant use of promethazine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of quetiapine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Avoid coadministration of inotuzumab ozogamicin with quinidine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinidine administration is also associated with QT prolongation and TdP.
Quinine: (Major) Avoid coadministration of inotuzumab ozogamicin with quinine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Quinine has been associated with QT prolongation and rare cases of TdP.
Quizartinib: (Major) Concomitant use of quizartinib and inotuzumab ozogamicin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Avoid coadministration of inotuzumab ozogamicin with ranolazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
Relugolix: (Major) Avoid coadministration of inotuzumab with relugolix due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of inotuzumab with relugolix due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ribociclib: (Major) Avoid coadministration of inotuzumab ozogamicin with ribociclib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Ribociclib has also been shown to prolong the QT interval in a concentration-dependent manner.
Ribociclib; Letrozole: (Major) Avoid coadministration of inotuzumab ozogamicin with ribociclib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Ribociclib has also been shown to prolong the QT interval in a concentration-dependent manner.
Rilpivirine: (Major) Avoid coadministration of inotuzumab ozogamicin with rilpivirine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Major) Avoid coadministration of inotuzumab ozogamicin with risperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Romidepsin: (Major) Avoid coadministration of inotuzumab ozogamicin with romidepsin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Romidepsin has also been reported to prolong the QT interval.
Saquinavir: (Major) Avoid coadministration of inotuzumab ozogamicin with saquinavir due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Avoid coadministration of inotuzumab with selpercatinib due to the potential for additive QT prolongation and torsade de pointes. If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of sertraline and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Avoid coadministration of inotuzumab ozogamicin with halogenated anesthetics due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, monitor the ECG and electrolytes. Inotuzumab has been associated with QT interval prolongation. Halogenated anesthetics can also prolong the QT interval.
Siponimod: (Major) Avoid coadministration of siponimod and inotuzumab due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Iloperidone has been associated with QT prolongation. Inotuzumab has been associated with QT interval prolongation.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Avoid coadministration of inotuzumab ozogamicin with solifenacin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has also been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with inotuzumab due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Both drugs have been associated with QT interval prolongation.
Sotalol: (Major) Concomitant use of sotalol and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sunitinib: (Major) Avoid coadministration of inotuzumab with sunitinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
Tacrolimus: (Major) Avoid coadministration of inotuzumab ozogamicin with tacrolimus due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and tacrolimus have been associated with QT interval prolongation.
Tamoxifen: (Major) Concomitant use of tamoxifen and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Avoid coadministration of inotuzumab ozogamicin with telavancin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and telavancin have been associated with QT interval prolongation.
Tetrabenazine: (Major) Avoid coadministration of inotuzumab ozogamicin with tetrabenazine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
Thioridazine: (Contraindicated) Coadministration of inotuzumab ozogamicin with thioridazine is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Thioridazine is associated with a well-established risk of QT prolongation and TdP. Inotuzumab has also been associated with QT interval prolongation.
Tolterodine: (Major) Avoid coadministration of inotuzumab ozogamicin with tolterodine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of inotuzumab ozogamicin with toremifene due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and closely monitor during treatment. Correct hypokalemia or hypomagnesemia prior to administration of toremifene. Inotuzumab has been associated with QT interval prolongation. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trazodone: (Major) Concomitant use of trazodone and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Coadministration of inotuzumab ozogamicin with trifluoperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Trifluoperazine is also associated with a possible risk for QT prolongation.
Triptorelin: (Major) Avoid coadministration of inotuzumab with triptorelin due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Vandetanib: (Major) Avoid coadministration of vandetanib with inotuzumab due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and electrolytes at baseline and periodically during treatment; correct any electrolyte abnormalities. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Inotuzumab has also been associated with QT interval prolongation.
Vardenafil: (Major) Concomitant use of vardenafil and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Avoid coadministration of inotuzumab ozogamicin with vemurafenib due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and vemurafenib have been associated with QT interval prolongation.
Venlafaxine: (Major) Concomitant use of venlafaxine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voclosporin: (Major) Avoid concomitant use of inotuzumab and voclosporin due to the risk of additive QT prolongation. If concomitant use is necessary, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of inotuzumab ozogamicin with clarithromycin due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Major) Avoid coadministration of inotuzumab ozogamicin with voriconazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Voriconazole has been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Major) Avoid coadministration of inotuzumab ozogamicin with vorinostat due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and vorinostat have been associated with QT interval prolongation.
Ziprasidone: (Major) Avoid coadministration of inotuzumab ozogamicin with ziprasidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ziprasidone has been associated with a possible risk for QT prolongation and/or TdP.

Inotuzumab ozogamicin Intravenous Inj Pwd: 0.9mg

0.8 mg/m2 IV on day 1 and 0.5 mg/m2 IV on days 8 and 15.

0.8 mg/m2 IV on day 1 and 0.5 mg/m2 IV on days 8 and 15.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate. CD22 is expressed on pre-B-cells and mature B-cells. Inotuzumab ozogamicin consists of a cytotoxic agent, N-acetyl-gamma-calicheamicin, covalently linked to a humanized anti-CD22 IgG4 monoclonal antibody. N-acetyl-gamma-calicheamicin is a natural product of Micromonospora echinospora; it induces double-strand DNA breaks resulting in cell cycle arrest and apoptotic cell death. Inotuzumab ozogamicin binds to CD22-expressing tumor cells where it becomes internalized in the B-cell and N-acetyl-gamma-calicheamicin dimethylhydrazide is released via hydrolytic cleavage of the link.

Inotuzumab ozogamicin is administered intravenously. Its volume of distribution is approximately 12 L. N-acetyl-gamma-calicheamicin dimethylhydrazide is about 97% bound to human plasma proteins in vitro. The steady-state clearance was 0.0333 L/hour and the terminal half-life was 12.3 days in 234 patients with relapsed or refractory acute lymphoblastic leukemia who received inotuzumab ozogamicin in clinical trials. N-acetyl-gamma- calicheamicin is metabolized by nonenzymatic reduction in vitro; serum levels were usually below the limit of detection in humans.
 
Affected cytochrome P450 isoenzymes and transporters: P-gp
N-acetyl-gamma-calicheamicin dimethylhydrazide is a substrate of P-glycoprotein (P-gp). At clinically relevant concentrations, it does not appear that inotuzumab ozogamicin inhibits CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 or induces CYP1A2, CYP2B6, and CYP3A4. Additionally, N-acetyl-gamma-calicheamicin dimethylhydrazide does not appear to induce CYP1A2, CYP2B6, and CYP3A4 or inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5,UGT1A1, UGT1A4, UGT1A6, UGT1A9, UGT2B7, P-gp, breast cancer resistance protein (BCRP), organic anion transporter (OAT)1 and OAT3, organic cation transporter (OCT)2, and organic anion transporting polypeptide (OATP)1B1, or OATP1B3 at clinically relevant concentrations.

Inotuzumab ozogamicin may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant while taking inotuzumab ozogamicin. Discuss the potential hazard to the fetus if inotuzumab ozogamicin is used during pregnancy or if a patient becomes pregnant while taking this drug. Embryo-fetal toxicities including increased resorptions, fetal growth retardation, and delayed skeletal ossification were observed when inotuzumab ozogamicin was administered to pregnant rats during organogenesis at doses resulting in exposures of approximately 2-times the exposure in humans (at the maximum recommended dose). Additionally, fetal growth retardation occurred in at inotuzumab ozogamicin doses resulting in exposures approximately 0.4-times the exposure in humans.

It is not known if inotuzumab ozogamicin or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants from inotuzumab ozogamicin, women should discontinue breast-feeding during inotuzumab ozogamicin therapy and for at least 2 months after the last dose.