Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 0.9mg/vial
Acute Lymphoblastic Leukemia
Indicated for relapsed/refractory B-cell precursor acute lymphoblastic leukemia
See Dosing Considerations
Cycle 1 for all patients
- Total dose of inotuzumab: 1.8 mg/m² per 21-day cycle, administered as 3 divided doses
- Day 1: 0.8 mg/m²
- Day 8 and 15: 0.5 mg/m²
- Duration of cycle 1 is 21 days; may extend to 28 days (eg, 7-day treatment-free interval starting on day 21) if patient achieves a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or to allow recovery from toxicity
- CR is defined as < 5% blasts in bone marrow and absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 10^9/L and absolute neutrophil counts [ANC] ≥ 1 × 10^9/L) and resolution of any extramedullary disease
- CRi is defined as < 5% blasts in bone marrow and absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets < 100 × 10^9/L and/or ANC < 1 × 10^9/L) and resolution of any extramedullary disease
Patients who achieve a CR or CRi
- Total dose of inotuzumab is 1.5 mg/m² per 28-day cycle, including a 7-day treatment-free interval starting on day 21, administered as 3 divided doses
- Day 1, 8, and 15: 0.5 mg/m² IV
Patients who do not achieve a CR or CRi
- Total dose of inotuzumab is 1.8 mg/m² per 28-day cycle, including a 7-day treatment-free interval starting on day 21 administered as 3 divided doses
- Day 1: 0.8 mg/m² IV
- Day 8 and 15: 0.5 mg/m² IV
- Patients who do not achieve a CR or CRi ≤3 cycles should discontinue treatment
Dosage Modifications
Renal impairment
- Mild to moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
- End-stage renal disease (CrCl <30 mL/min) and/or hemodialysis: Safety and efficacy is not established
Hepatic impairment
- Total bilirubin (≤1.5x ULN) and AST/ALT (≤2.5x ULN): No dosage adjustment necessary
- Total bilirubin >1.5x ULN and/or AST/ALT >2.5x ULN: Limited safety information; caution with use
Doses within a treatment cycle (eg, Days 8 and/or 15) do not need to be interrupted due to neutropenia or thrombocytopenia but interruptions within a cycle are recommended for non-hematologic toxicities; if dose is reduced due to drug related toxicity, it must not be re-escalated
Hematologic toxicities
- Baseline absolute neutrophil count (ANC) ≥1 × 10^9/L: If ANC decreases, then interrupt next cycle until ANC ≥1 × 10^9/L; discontinue inotuzumab if low ANC persists for >28 days and is considered an inotuzumab-related toxicity
- Baseline platelet count >50 × 10^9; /L: If platelet count decreases, then interrupt next cycle if platelet count was ≥50 × 10^9 /L; discontinue inotuzumab if low platelet count persists >28 days and is considered an inotuzumab-related toxicity
Baseline ANC>1 × 10^9 /L and/or platelet count <50 × 10^9 /L
- If ANC or platelet count decreases, then interrupt next cycle of treatment until at least one of following occurs:
- ANC and platelet count recover to at least baseline levels for prior cycle
- ANC recovers ≥1 × 10^9 /L and platelet count ≥50 × 10^9 /L
- Stable/improved disease (based on most recent bone marrow assessment) and ANC and platelet count decrease is correlated to the underlying disease (not considered to be inotuzumab-related toxicity)
Nonhematologic toxicities
- Venoocclusive disease (VOD) or other severe liver disease: Permanently discontinue
- Nonhematologic toxicity grade 2 or higher: Interrupt treatment until recovery to
Total bilirubin >1.5x ULN and AST/ALT >2.5x ULN
- Interrupt dosing until recovery of total bilirubin ≤1.5x ULN and AST/ALT ≤2.5x ULN prior to each dose unless due to Gilbert syndrome or hemolysis
- Permanently discontinue treatment if total bilirubin does not recover ≤1.5x ULN or AST/ALT ≤2.5x ULN
Infusion-related reactions
- Interrupt infusion and institute appropriate medical management; depending on severity of infusion-related reaction, consider discontinuation of infusion or administration of steroids and antihistamines
- Severe or life-threatening infusion reactions: Permanently discontinue treatment
Dose modifications depending on dosing interruption
- <7 days (within a cycle): Interrupt next dose (maintain a minimum of 6 days between doses)
- ≥7 days: Omit next dose within current cycle
- ≥14 days: Once adequate recovery is achieved, decrease total dose by 25% for subsequent cycle; if further dose modifications are required, decrease number of doses to 2 per cycle for subsequent cycles; if dosing modifications are not tolerated, then permanently discontinue treatment
Dosing Considerations
Premedication with a corticosteroid, antipyretic, and antihistamine is recommended prior to dosing
Observe patient during and for at least 1 hr post infusion for infusion-related signs/symptoms
Prior to initial dose, in patients with circulating lymphoblasts, cytoreduction with a combination of hydroxyurea, steroids, and/or vincristine is recommended to achieve a peripheral blast count ≤10,000/mm³
Patients proceeding to hematopoietic stem cell transplantation (HSCT): Duration of inotuzumab treatment is 2 cycles; patients who do not achieve CR or CRi and minimal residual disease (MRD) negativity after 2 cycles may consider a third cycle
Patients not proceeding to HSCT: Additional cycles may be administered; not to exceed 6 cycles
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (128)
- adagrasib
adagrasib, inotuzumab. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
- alfuzosin
inotuzumab and alfuzosin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
alfuzosin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. - amiodarone
inotuzumab and amiodarone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- amisulpride
amisulpride and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
- anagrelide
inotuzumab and anagrelide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- apomorphine
inotuzumab and apomorphine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- arformoterol
inotuzumab and arformoterol both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- aripiprazole
aripiprazole and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- arsenic trioxide
inotuzumab and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- artemether
inotuzumab and artemether both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- artemether/lumefantrine
inotuzumab and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- asenapine
inotuzumab and asenapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- asenapine transdermal
asenapine transdermal and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- atomoxetine
atomoxetine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- azithromycin
inotuzumab and azithromycin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- bedaquiline
inotuzumab and bedaquiline both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- buprenorphine
buprenorphine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine buccal
buprenorphine buccal and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine subdermal implant
buprenorphine subdermal implant and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine transdermal
buprenorphine transdermal and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- ceritinib
inotuzumab and ceritinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- chloroquine
inotuzumab and chloroquine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- chlorpromazine
inotuzumab and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- chlorpropamide
inotuzumab and chlorpropamide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- ciprofloxacin
inotuzumab and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- citalopram
inotuzumab and citalopram both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- clarithromycin
inotuzumab and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- clozapine
inotuzumab and clozapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- crizotinib
inotuzumab and crizotinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- dasatinib
dasatinib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- deferiprone
deferiprone, inotuzumab. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- degarelix
inotuzumab and degarelix both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- desflurane
desflurane and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- disopyramide
inotuzumab and disopyramide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- dofetilide
inotuzumab and dofetilide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
dofetilide increases toxicity of inotuzumab by QTc interval. Avoid or Use Alternate Drug. - dolasetron
inotuzumab and dolasetron both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- donepezil
donepezil and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- doxepin
doxepin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- droperidol
inotuzumab and droperidol both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- efavirenz
efavirenz and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- eliglustat
eliglustat and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- encorafenib
encorafenib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- entrectinib
inotuzumab and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.
- eribulin
inotuzumab and eribulin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- erythromycin base
inotuzumab and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- erythromycin ethylsuccinate
inotuzumab and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- erythromycin lactobionate
inotuzumab and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- erythromycin stearate
inotuzumab and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- escitalopram
escitalopram increases toxicity of inotuzumab by QTc interval. Avoid or Use Alternate Drug.
- ezogabine
inotuzumab and ezogabine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- fexinidazole
fexinidazole and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
- fingolimod
inotuzumab and fingolimod both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- flecainide
inotuzumab and flecainide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- fluconazole
inotuzumab and fluconazole both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- formoterol
inotuzumab and formoterol both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- gemifloxacin
inotuzumab and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- gilteritinib
gilteritinib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- glasdegib
inotuzumab and glasdegib both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, monitor for increased risk of QTc interval prolongation.
- goserelin
inotuzumab and goserelin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- granisetron
inotuzumab and granisetron both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- haloperidol
inotuzumab and haloperidol both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- histrelin
inotuzumab and histrelin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- ibutilide
inotuzumab and ibutilide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- iloperidone
inotuzumab and iloperidone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- indacaterol, inhaled
inotuzumab and indacaterol, inhaled both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- isoflurane
isoflurane and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- itraconazole
itraconazole and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
- lapatinib
inotuzumab and lapatinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- lefamulin
lefamulin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- lenvatinib
inotuzumab and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- leuprolide
inotuzumab and leuprolide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- levofloxacin
inotuzumab and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- lithium
lithium and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- lopinavir
inotuzumab and lopinavir both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- lumefantrine
inotuzumab and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- macimorelin
macimorelin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.
- methadone
inotuzumab and methadone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- mifepristone
inotuzumab and mifepristone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- mirtazapine
mirtazapine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- mobocertinib
mobocertinib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.
- moxifloxacin
inotuzumab and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- nilotinib
inotuzumab and nilotinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- ofloxacin
inotuzumab and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- olanzapine
olanzapine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- ondansetron
inotuzumab and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- osimertinib
inotuzumab and osimertinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- oxaliplatin
oxaliplatin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- palifermin
palifermin increases toxicity of inotuzumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- paliperidone
inotuzumab and paliperidone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- panobinostat
inotuzumab and panobinostat both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pasireotide
inotuzumab and pasireotide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pazopanib
inotuzumab and pazopanib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pentamidine
inotuzumab and pentamidine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- perflutren
inotuzumab and perflutren both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pimavanserin
inotuzumab and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pimozide
inotuzumab and pimozide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- pitolisant
inotuzumab and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.
- primaquine
primaquine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- procainamide
inotuzumab and procainamide both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- propafenone
inotuzumab and propafenone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- quetiapine
inotuzumab and quetiapine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- quinidine
inotuzumab and quinidine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- ranolazine
inotuzumab and ranolazine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- ribociclib
inotuzumab and ribociclib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
ribociclib increases toxicity of inotuzumab by QTc interval. Avoid or Use Alternate Drug. - romidepsin
inotuzumab and romidepsin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- saquinavir
inotuzumab and saquinavir both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- sertraline
sertraline and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- sevoflurane
sevoflurane and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- siponimod
siponimod and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- solifenacin
solifenacin and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- sorafenib
inotuzumab and sorafenib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- sotalol
inotuzumab and sotalol both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- sunitinib
inotuzumab and sunitinib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- tacrolimus
tacrolimus and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- telavancin
inotuzumab and telavancin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- tetrabenazine
inotuzumab and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- thioridazine
inotuzumab and thioridazine both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- toremifene
inotuzumab and toremifene both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- trazodone
inotuzumab and trazodone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- triptorelin
inotuzumab and triptorelin both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- vandetanib
inotuzumab and vandetanib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- vemurafenib
inotuzumab and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- voriconazole
inotuzumab and voriconazole both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
- vorinostat
vorinostat and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- ziprasidone
inotuzumab and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid concomitant use, obtain ECGs and electrolytes before and after initiation of any drug known to prolong QTc, and periodically monitor as clinically indicated during treatment.
Monitor Closely (19)
- albuterol
albuterol and inotuzumab both increase QTc interval. Use Caution/Monitor.
- chloroquine
chloroquine increases toxicity of inotuzumab by QTc interval. Use Caution/Monitor.
- deutetrabenazine
inotuzumab and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
- fostemsavir
inotuzumab and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- gadobenate
gadobenate and inotuzumab both increase QTc interval. Use Caution/Monitor.
- gemtuzumab
inotuzumab and gemtuzumab both increase QTc interval. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and inotuzumab both increase QTc interval. Modify Therapy/Monitor Closely. If coadministration necessary, obtain baseline ECG to assess initial QT interval and determine frequency of subsequent monitoring; avoid non-essential QT prolonging drug and correct electrolyte imbalances
- ofatumumab SC
ofatumumab SC, inotuzumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- osilodrostat
osilodrostat and inotuzumab both increase QTc interval. Use Caution/Monitor.
- oxaliplatin
oxaliplatin will increase the level or effect of inotuzumab by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.
- ozanimod
ozanimod and inotuzumab both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
- ponesimod
ponesimod and inotuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- selpercatinib
selpercatinib increases toxicity of inotuzumab by QTc interval. Use Caution/Monitor.
- siponimod
siponimod and inotuzumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- trastuzumab
trastuzumab, inotuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- trastuzumab deruxtecan
trastuzumab deruxtecan, inotuzumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- triclabendazole
triclabendazole and inotuzumab both increase QTc interval. Use Caution/Monitor.
- valbenazine
valbenazine and inotuzumab both increase QTc interval. Use Caution/Monitor.
- voclosporin
voclosporin, inotuzumab. Either increases effects of the other by QTc interval. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
Thrombocytopenia (51%)
Neutropenia (49%)
Infection (48%)
Neutropenia, grade 3 or higher (48%)
Thrombocytopenia, grade 3 or higher (42%)
Anemia (36%)
Leukopenia (35%)
Fatigue (35%)
Hemorrhage (33%)
Leukopenia, grade 3 or higher (33%)
Pyrexia (32%)
Nausea (31%)
Headache (28%)
Infection, grade 3 or higher (28%)
Febrile neutropenia (26%)
Transaminases increased (26%)
Anemia, grade 3 or higher (24%)
Abdominal pain (23%)
Hyperbilirubinemia (21%)
Gamma-glutamyltransferase increased (21%)
Lymphopenia (18%)
Diarrhea (17%)
Constipation (16%)
Lymphopenia, grade 3 or higher (16%)
Vomiting (15%)
Stomatitis (13%)
Alkaline phosphatase increased (13%)
Decreased appetite (12%)
Chills (11%)
1-10%
Grade 3 or higher
- Gamma-glutamyltransferase increased (10%)
- Transaminases increased (7%)
- Hemorrhage (5%)
- Fatigue (5%)
- Hyperbilirubinemia (5%)
- Pyrexia (3%)
- Abdominal pain (3%)
- Headache (2%)
- Alkaline phosphatase increased (2%)
- Stomatitis (2%)
- Nausea (2%)
- Decreased appetite (1%)
- Vomiting (1%)
- Diarrhea (1%)
Warnings
Black Box Warnings
Hepatoxicity, including VOD
- Hepatotoxicity, including fatal and life-threatening VOD (also known as sinusoidal obstruction syndrome) reported with relapsed or refractory acute lymphoblastic leukemia (ALL) who received inotuzumab
- Risk of VOD was greater in patients who underwent HSCT after inotuzumab treatment; use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin level ≥ULN before HSCT were significantly associated with an increased risk of VOD
- Other risk factors include ongoing or prior liver disease, prior HSCT, increased age, later salvage lines, and a greater number of inotuzumab treatment cycles
- Elevation of liver tests may require dosing interruption, dose reduction, or permanent discontinuation of inotuzumab; permanently discontinue treatment if VOD occurs
- If severe VOD occurs, treat according to standard medical practice
Increased risk of post-HSCT nonrelapse mortality
- Reports of higher post-HSCT nonrelapse mortality rate in patients receiving inotuzumab, resulting in a higher Day 100 post-HSCT mortality rate
- In a clinical trial, the post-HSCT nonrelapse mortality rate was 31/79 (39%) and 8/35 (23%) in inotuzumab arm compared with the investigator’s choice of chemotherapy arm
- In inotuzumab arm, the most common causes of post-HSCT nonrelapse mortality included VOD and infections
- Monitor toxicities post-HSCT, including signs and symptoms of infection and VOD
Contraindications
None
Cautions
Hepatotoxicity, including VOD, reported; monitor closely for signs and symptoms of VOD (eg, increased total bilirubin, hepatomegaly, rapid weight gain, ascites) (see Black Box Warnings)
Increase risk of posttransplant nonrelapse mortality (see Black Box Warnings)
QT prolongation reported; caution with history of or predisposition to QT prolongation, currently taking medications known to prolong QT interval, or electrolyte disturbances; obtain baseline ECG and electrolytes levels; monitor periodically during treatment
In animal studies, embryofetal harm may occur when administered to a pregnant woman (see Pregnancy)
Myelosuppression
- Risk of myelosuppression; complications, including infections and bleeding/hemorrhagic events, observed; monitor complete blood cell counts prior to initiating; monitor for signs/symptoms of infection, bleeding/hemorrhage, or other effects of myelosuppression during treatment; if necessary, administer prophylactic anti-infectives and use surveillance testing during and after treatment
- Management of severe infection, bleeding/hemorrhage, or other effects of myelosuppression, including severe neutropenia or thrombocytopenia, may require dosing interruption, dose reduction, or permanent discontinuation
Infusion-related reactions
- Infusion-related reactions may occur; premedicate with a corticosteroid, antipyretic, and antihistamine prior to dosing
- Monitor closely during and for at least 1 hr after the end of infusion for potential onset of infusion-related reactions (eg, fever, chills, rash, or breathing problems); interrupt infusion and institute appropriate medical management if an infusion-related reaction occurs
- See Dosage Modifications
Pregnancy
Pregnancy
Based on its mechanism of action and findings from animal studies, inotuzumab can cause embryofetal harm when administered to a pregnant woman; no available data for use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage
If used during pregnancy, or if patient becomes pregnant while taking inotuzumab, advise patient of the potential risk to a fetus
Animal data
- In rat embryofetal development studies, inotuzumab ozogamicin caused embryofetal toxicity at maternal systemic exposures that were ≥0.4 times exposure in patients at maximum recommended dose, based on AUC; pregnant rats received daily IV doses of inotuzumab ozogamicin up to 0.36 mg/m² during organogenesis; embryofetal toxicities, including increased resorptions and fetal growth restriction, as evidenced by decreased live fetal weights and delayed skeletal ossification, were observed at ≥0.11 mg/m² (~2 times the exposure in patients at maximum recommended dose, based on AUC); fetal growth restriction also occurred at 0.04 mg/m² (~0.4 times the exposure in patients at the maximum recommended dose, based on AUC)
Females and Males of Reproductive Potential
- Based on findings in animals, inotuzumab may impair fertility in males and females of reproductive potential
Pregnancy testing
- Verify the pregnancy status of females of reproductive potential prior to initiating inotuzumab
Contraception
- Advise females of reproductive potential to avoid becoming pregnant while receiving inotuzumab
- Advise females of reproductive potential to use effective contraception during treatment with inotuzumab and for at least 8 months after the last dose
- Advise males with female partners of reproductive potential to use effective contraception during treatment with inotuzumab and for at least 5 months after the last dose
Lactation
Unknown if distributed in human breast milk
No data on presence of inotuzumab ozogamicin or its metabolites in human milk, its effects on breastfed infant, or effects on milk production
Because of potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with inotuzumab and for at least 2 months after the last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
CD22-directed antibody-drug conjugate (ADC) recognizes human CD22; small molecule, N-acetyl-gamma-calicheamicin, is a cytotoxic agent that covalently attaches to antibody via a linker
Nonclinical data suggest anticancer activity of inotuzumab ozogamicin is due to binding of ADC to CD22-expressing tumor cells, followed by internalization of ADC-CD22 complex, and ultimately activating N-acetyl-gamma-calicheamicin 19 dimethylhydrazide, which induces double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death
Absorption
Peak plasma concentration: 308 ng/mL
AUC: 100,000 ng·h/mL
Steady-state drug concentration was achieved by cycle 4
Distribution
Protein bound: 97%
Vd: ~12 L
Metabolism
N-acetyl-gamma-calicheamicin dimethylhydrazide was primarily metabolized via nonenzymatic reduction
Elimination
Clearance, steady state: 0.0333 L/h
Half-life: 12.3 days
Administration
IV Compatibilities
0.9% NaCl
IV Preparation
Reconstitute each vial with 4 mL of sterile water for injection; reconstituted concentration 0.25 mg/mL
Gently swirl vial to aid dissolution
Do not shake; inspect reconstituted solution for particulates and discoloration; reconstituted solution should be clear to opalescent, colorless to slightly yellow, and free of visible foreign matter
Use reconstituted solution immediately or after being refrigerated (2-8°C; 36-46°F) for up to 4 hr
Aseptically withdraw calculated amount from vial(s) using a syringe (see full prescribing information for calculation and further preparation information); discard any unused reconstituted solution left in vial
Add reconstituted solution to an infusion container with 0.9% NaCl to a total volume of 50 mL
Infusion container made of polyvinyl chloride (PVC), DEHP, non-DEHP-containing polyolefin (polypropylene and/or polyethylene), or ethylene vinyl acetate (EVA) is recommended
Gently invert infusion container to mix diluted solution; do not shake
IV Administration
Filtration is not required: if diluted solution is filtered, polyethersulfone (PES)-, polyvinylidene fluoride (PVDF)-,or hydrophilic polysulfone (HPS)-based filters are recommended
Do not use filters made of nylon or mixed cellulose ester (MCE)
Administer diluted solution with 8 hr of reconstitution (from reconstitution through end of administration)
Infuse diluted solution over 1 hr at a rate of 50 mL/hr at room temperature (20-25°C; 68-77°F)
Infusion lines made of PVC, DEHP-, or non-DEHP-containing, polyolefin (polypropylene and/or polyethylene), or polybutadiene are recommended
Do not mix or administer inotuzumab with other medicinal products
Storage
All formulations: Protect from light and do not freeze
Lyophilized powder vial: Refrigerate (2-8°C; 36-46°F) vials and store in original carton
Reconstituted vial: Refrigerate (2-8°C; 36-46°F) for up to 4 hr
Diluted solution
- After start of dilution: Store at room temperature (20-25°C; 68-77°F) for up to 4 hr or refrigerate (2-8°C; 36-46°F) for up to 3 hr
During administration
- Store in refrigerator (2-8°C; 36-46°F); allow it to equilibrate at room temperature (20-25°C; 68-77°F); maximum time from reconstitution through end of administration ≤8 hr
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
