Mylotarg

Antineoplastic Monoclonal Antibodies Targeting CD33
Antineoplastic Monoclonal Antibody-Drug Conjugates (ADCs)

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
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
Pediatrics:
Doses 3 to 9 mg/m2: Moderate
Adults:
Low
Administer routine antiemetic prophylaxis prior to treatment.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Gemtuzumab ozogamicin is available as a single-dose, preservative-free, 4.5-mg lyophilized powder vial.
Premedication with acetaminophen, diphenhydramine, and a corticosteroid prior to each dose is recommended; observe patients during and for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions.
 
Reconstitution
Calculate the number of vials needed for the dose; allow the lyophilized vials to reach room temperature for approximately 5 minutes.
Add 5 mL of Sterile Water for Injection to each vial for a final vial concentration of 1 mg/mL (4.5 mg in 4.5 mL); gently swirl the vial to dissolve powder but do not shake.
The reconstitution solution may contain small white to off-white, opaque to translucent, and amorphous to fiber-like particles.
Storage of reconstituted vials: if not further diluted immediately, vials may be stored in the refrigerator (at 2 to 8 degrees C or 36 to 46 degrees F) for up to 1 hour after reconstitution; protect from light and do not freeze.
 
Dilution
Doses less than 3.9 mg: add the required dose/volume of gemtuzumab ozogamicin from the reconstituted vial into a syringe with 0.9% Sodium Chloride Injection to achieve a final concentration between 0.075 and 0.234 mg/mL; protect from light.
Doses of 3.9 mg or greater: add the required dose/volume of gemtuzumab ozogamicin from the reconstituted vial into a syringe with 0.9% Sodium Chloride Injection OR to an IV bag with 0.9% Sodium Chloride Injection to achieve a final concentration between 0.075 and 0.234 mg/mL; protect from light.
Gently invert the syringe or infusion bag to mix the diluted solution but do not shake.
Storage of admixture: if not infused immediately, the diluted solution may be stored at room temperature (15 to 25 degrees C or 59 to 77 degrees F) for up to 6 hours (includes the infusion time) or refrigerated (2 to 8 degrees C or 36 to 46 degrees F) for up to 12 hours (includes the infusion time, time to equilibrate to room temperature, and the 1 hour vial post-reconstitution); protect from light and do not freeze.
 
Intravenous (IV) Infusion
Allow refrigerated admixtures to warm to room temperature for approximately 1 hour prior to administration.
Doses less than 3.9 mg must be administered via syringe.
Using an in-line 0.2 micron polyethersulfone (PES) filter, administer gemtuzumab ozogamicin as an IV infusion over 2 hours.
Protect the syringe or IV bag from light using a light-blocking cover during the infusion; the infusion line does not need protection from light.
Do not mix with or administer as an infusion with other drugs.

Severe

infection / Delayed / 0-55.0
hepatotoxicity / Delayed / 0-51.0
hyponatremia / Delayed / 0-44.0
cardiotoxicity / Delayed / 0-28.0
bleeding / Early / 6.0-21.0
anorexia / Delayed / 0-19.0
fever / Early / 0-16.0
elevated hepatic enzymes / Delayed / 0-14.0
fatigue / Early / 0-12.0
oral ulceration / Delayed / 0-11.0
rash / Early / 0-11.0
hyperglycemia / Delayed / 0-11.0
hypotension / Rapid / 0-9.0
hyperbilirubinemia / Delayed / 0-8.0
nausea / Early / 0-7.0
hypoxia / Early / 0-7.0
nephrotoxicity / Delayed / 0-6.0
veno-occlusive disease (VOD) / Delayed / 0-5.0
sinusoidal obstruction syndrome (SOS) / Delayed / 0-5.0
diarrhea / Early / 0-5.0
intracranial bleeding / Delayed / 0-3.0
subdural hematoma / Early / 0-3.0
headache / Early / 0-2.0
sinus tachycardia / Rapid / 0-2.0
pulmonary edema / Early / 2.0
colitis / Delayed / Incidence not known
hemorrhagic cystitis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

neutropenia / Delayed / 0-100.0
anemia / Delayed / 0-100.0
thrombocytopenia / Delayed / 0-100.0
hypophosphatemia / Delayed / 0-64.0
hypokalemia / Delayed / 0-57.0
constipation / Delayed / 0-21.0
ascites / Delayed / Incidence not known
hepatomegaly / Delayed / Incidence not known
antibody formation / Delayed / Incidence not known
infusion-related reactions / Rapid / Incidence not known

Mild

vomiting / Early / 0-21.0
weight gain / Delayed / Incidence not known
chills / Rapid / Incidence not known

Hepatic disease, hepatotoxicity, sinusoidal obstruction syndrome (SOS), veno-occlusive disease (VOD)

Hepatotoxicity including severe or fatal veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) has been reported with gemtuzumab ozogamicin given as monotherapy or in combination with other chemotherapy agents. Monitor liver function tests (LFTs) including total bilirubin and alkaline phosphatase levels prior to each gemtuzumab ozogamicin dose and at least 3 times per week until resolution of treatment-related toxicity. Additionally, increase the frequency of LFT monitoring if abnormal LFTs are observed and in patients who undergo a hematopoietic stem-cell transplant (HSCT). A dose delay or omission may be required in patients who develop hepatotoxicity. Closely monitor patients during and after treatment 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 one study, the median time to onset of VOD/SOS was 9 days (range, 2 to 298 days). The risk of VOD/SOS may be greater in patients who receive higher doses of single-agent gemtuzumab ozogamicin; pre-existing moderate or severe hepatic disease/impairment, gemtuzumab ozogamicin treatment for relapsed disease after a HSCT, and a HSCT after gemtuzumab ozogamicin therapy increased the risk of VOD/SOS by 8.7-fold, 2.6-fold, and 2.9-fold, respectively. In 2 clinical studies, a 2 and 3.5 month interval between gemtuzumab ozogamicin therapy and a HSCT was recommended.

Mylotarg

Rx

A CD33-directed antibody-drug conjugate
Used in patients aged 1 month and older with newly diagnosed AML and in patients aged 2 years and older with relapsed or refractory AML
Severe or life-threatening hepatotoxicity including veno-occlusive disease/sinusoidal obstruction syndrome has been reported

For the treatment of acute myelogenous leukemia (AML).
NOTE: Gemtuzumab ozogamicin has been designated by the FDA as an orphan drug for the treatment of AML.
For the treatment of newly diagnosed, CD33-positive AML as a single agent. Intravenous dosage Adults

6 mg/m2 IV on day 1 and 3 mg/m2 IV on day 8 as induction therapy. Patients without disease progression may receive gemtuzumab ozogamicin 2 mg/m2 on day 1 repeated every 4 weeks for up to 8 cycles. Therapy delay or interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate patients with acetaminophen 650 mg PO and diphenhydramine 50 mg IV or PO 1 hour prior to the infusion; administer methylprednisolone 1 mg/kg IV (or equivalent) within 30 minutes prior to the infusion. Observe patients for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial dose; an additional corticosteroid dose may be given if patients develop an infusion reaction during or within 4 hours the infusion. Administer cytoreduction therapy prior to giving the first dose of gemtuzumab ozogamicin in patients with a leukocyte count greater than 30 X 109 cells/L. The median overall survival time (primary endpoint) was significantly improved in patients (median age, 77 years; range, 62 to 88 years) with previously untreated AML who received single-agent gemtuzumab ozogamicin compared with best supportive care (4.9 months vs. 3.6 months; hazard ratio = 0.69; 95% CI, 0.53 to 0.9) in a multicenter, randomized, phase 3 trial (n = 237; the EORTC-GIMEMA AML-19 trial). Eligible patients either were not candidates for intensive chemotherapy (e.g., greater than 75 years of age) or were 61 to 75 years of age and had a WHO performance score greater than 2 or were unwilling to receive standard chemotherapy. A median of 3 gemtuzumab ozogamicin infusions were administered in this trial (range, 1 to 10 infusions).

For the treatment of newly diagnosed, de novo, CD33-positive AML in combination with daunorubicin and cytarabine. Intravenous dosage Adults

3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 in combination with daunorubicin and cytarabine as induction therapy; if a second course of induction therapy is necessary, omit gemtuzumab ozogamicin. As consolidation therapy, administer gemtuzumab ozogamicin 3 mg/m2 (maximum dose of 4.5 mg) IV on day 1 in combination with daunorubicin and cytarabine for up to 2 consolidation courses. Therapy delay or interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate patients with acetaminophen 650 mg PO and diphenhydramine 50 mg IV or PO 1 hour prior to the infusion; administer methylprednisolone 1 mg/kg IV (or equivalent) within 30 minutes prior to the infusion. Observe patients for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial dose; an additional corticosteroid dose may be given if patients develop an infusion reaction during or within 4 hours the infusion. Administer cytoreduction therapy prior to giving the first dose of gemtuzumab ozogamicin in patients with a leukocyte count greater than 30 X 109 cells/L. At a median follow-up time of 14.8 months, the median event-free survival time (primary endpoint) was significantly improved in patients aged 50 to 70 years with newly-diagnosed de novo AML who received gemtuzumab ozogamicin, daunorubicin, and cytarabine compared with daunorubicin and cytarabine alone (15.6 months vs. 9.7 months; hazard ratio = 0.58; 95% CI, 0.43 to 0.78) in a multicenter, randomized, phase 3 trial (n = 278; the ALFA-0701 trial). In 58 patients with unfavorable cytogenetics, event-free survival (HR = 1.03; 95% CI, 0.5 to 2.13) and overall survival (HR = 1.44; 95% CI, 0.65 to 3.18) were worse in patients who received gemtuzumab ozogamicin. Consider the patient's cytogenetic status and perform a benefit/risk assessment of continuing gemtuzumab ozogamicin treatment. The dosage of daunorubicin was 60 mg/m2 IV daily on days 1, 2, and 3 as induction therapy (60 mg/m2 IV daily on day 1 and 2 for the second induction cycle if needed) and 60 mg/m2 IV on day 1 only of course 1 and 60 mg/m2 IV daily on days 1 and 2 of course 2 as consolidation therapy. The dosage of cytarabine was 200 mg/m2 IV daily on days 1 to 7 as induction therapy (1 gram/m2 IV every 12 hours on days 1, 2, and 3 for the second induction cycle if needed) and 1 gram/m2 IV every 12 hours on days 1, 2, 3 and 4 as consolidation therapy. An allogeneic transplantation was permitted after a delay of at least 2 months following gemtuzumab ozogamicin therapy.

For the treatment of relapsed or refractory CD33-positive AML. Intravenous dosage Adults

3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as a single course of induction therapy. Therapy delay or interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate patients with acetaminophen 650 mg PO and diphenhydramine 50 mg IV or PO 1 hour prior to the infusion; administer methylprednisolone 1 mg/kg IV (or equivalent) within 30 minutes prior to the infusion. Observe patients for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial dose; an additional corticosteroid dose may be given if patients develop an infusion reaction during or within 4 hours the infusion. Administer cytoreduction therapy prior to giving the first dose of gemtuzumab ozogamicin in patients with a leukocyte count greater than 30 X 109 cells/L. The complete remission rate was 26% following a single course of gemtuzumab ozogamicin in adult patients (median age, 64 years; range, 22 to 80 years) with CD33-positive AML in first relapse in a nonrandomized phase 2 trial (n = 57); the median duration of remission was 10 months. The median relapse-free survival was 11.6 months. Patients received consolidation therapy with cytarabine (3 grams/m2 IV every 12 hours for 3 days in patients less than 55 years old; 1 gram/m2 IV every 12 hours for 3 days in patients 55 years and older or who had a creatinine clearance less than 50 mL/min); hematopoietic stem cell transplantation was permitted after a delay of at least 90 days following gemtuzumab ozogamicin therapy.

Adolescents and Children 2 years and older

3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as a single course of therapy. Therapy delay or interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate patients with acetaminophen 15 mg/kg (maximum dose of 650 mg) PO and diphenhydramine 1 mg/kg (maximum dose of 50 mg) IV or PO 1 hour prior to the infusion; administer methylprednisolone 1 mg/kg IV or PO (or equivalent) within 30 minutes prior to the infusion. Observe patients for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial dose; an additional corticosteroid dose may be given if patients develop an infusion reaction during or within 4 hours the infusion. Administer cytoreduction therapy prior to giving the first dose of gemtuzumab ozogamicin in patients with a leukocyte count greater than 30 X 109 cells/L. The safety and efficacy of single agent gemtuzumab ozogamicin in the pediatric patients with relapsed or refractory AML was supported by a single-arm trial (n = 29). In this trial, 13 patients were 2 to 11 years of age and 15 patients were 12 to 18 years of age. Additionally, efficacy and safety of gemtuzumab ozogamicin have been evaluated in 96 patients aged 0.2 to 21 years of age in a review of the literature.

For the treatment of newly diagnosed, de novo, CD33-positive AML in combination with multi-agent standard chemotherapy. Intravenous dosage Adolescents, Children, and Infants

3 mg/m2 IV for 2 doses in patients with a body surface area (BSA) of 0.6 m2 or greater OR 0.1 mg/kg IV for 2 doses in patients with BSA less than 0.6 m2; give the calculated dose as an IV infusion once in induction cycle 1 on day 6 and once in intensification cycle 2 on day 7. Gemtuzumab ozogamicin is administered in combination with multi-agent standard chemotherapy during the first induction cycle and second intensification cycle only. Therapy delay or interruption, dose reduction, or permanent discontinuation may be necessary in patients who develop toxicity. Premedicate patients with acetaminophen 15 mg/kg (maximum dose of 650 mg) PO and diphenhydramine 1 mg/kg (maximum dose of 50 mg) IV or PO 1 hour prior to the infusion; administer methylprednisolone 1 mg/kg IV or PO (or equivalent) within 30 minutes prior to the infusion. Observe patients for at least 1 hour after the end of the infusion for symptoms of infusion-related reactions. Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial dose; an additional corticosteroid dose may be given if patients develop an infusion reaction during or within 4 hours the infusion. Administer cytoreduction therapy prior to giving the first dose of gemtuzumab ozogamicin in patients with a leukocyte count greater than 30 X 109 cells/L. The 3-year event-free survival rate was significantly improved in patients (median age, 9.7 years) with newly diagnosed AML who received gemtuzumab ozogamicin plus intensive chemotherapy compared with patients who received intensive chemotherapy (53.1% vs. 46.9%; hazard ratio (HR) = 0.83; 95% CI, 0.7 to 0.99; p = 0.04) in a randomized, phase 3 trial (n = 1,022; AAML0531 trial). However, the 3-year overall survival rates were not significantly improved in patients in the gemtuzumab ozogamicin arm (69.4% vs. 65.4%; HR = 0.91; 95% CI, 0.74 to 1.13). Chemotherapy was given according to the Children's Oncology Group AAML0531 regimen and consisted of up to 5 cycles of chemotherapy as follows: cycle 1 and 2 of induction therapy (all patients); cycle 1 of intensification therapy (patients in remission after 2 cycles of induction); cycle 2 intensification therapy (patients in remission after cycle 1 of intensification therapy and no stem-cell transplant); and cycle 3 intensification therapy (patients in remission after cycle 2 of intensification therapy). Responding patients with intermediate- or high-risk AML could receive an allogeneic hematopoietic stem-cell transplantation after cycle 1 of intensification therapy. All patients received intrathecal cytarabine during treatment. Specific dosing was as follows: Induction, cycle 1: cytarabine 100 mg/m2 IV twice daily for 10 days (on days 1 to 10); daunorubicin 50 mg/m2 IV on days 1, 3, and 5; etoposide 100 mg/m2 IV daily for 5 days (on days 1, 2, 3, 4, and 5); and gemtuzumab IV once on day 6. Induction, cycle 2: cytarabine 100 mg/m2 IV twice daily for 8 days (on days 1 to 8); daunorubicin 50 mg/m2 IV on days 1, 3, and 5; and etoposide 100 mg/m2 IV daily for 5 days (on days 1, 2, 3, 4, and 5). Intensification, cycle 1: cytarabine 1,000 mg/m2 IV twice daily for 5 days (on days 1, 2, 3, 4, and 5) and etoposide 150 mg/m2 IV daily for 5 days (on days 1, 2, 3, 4, and 5). Intensification, cycle 2: mitoxantrone 12 mg/m2 IV daily on days 3, 4, 5, and 6 (4 doses); cytarabine 1,000 mg/m2 IV twice daily on days 1, 2, 3, and 4 (8 doses); and gemtuzumab IV once on day 7. Intensification, cycle 3: cytarabine 3,000 mg/m2 IV twice daily on days 1, 2, 8, and 9 (8 doses) and L-asparaginase 6,000 mg/m2 intramuscularly on days 2 and 9 (2 doses).

Hepatic Impairment

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
Total bilirubin level greater than 2-times the upper limit of normal (ULN) or AST or ALT levels greater than 2.5-times the ULN: Delay gemtuzumab ozogamicin treatment until the total bilirubin level is 2-times the ULN or less and AST or ALT levels are 2.5-times the ULN or less. Omit the scheduled dose if the delay lasts more than 2 days between sequential infusions.
Hepatic Veno-Occlusive Disease (VOD)/Sinusoidal obstruction syndrome (SOS)
Permanently discontinue therapy.

Renal Impairment

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 gemtuzumab 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: (Moderate) Use gemtuzumab ozogamicin and alfuzosin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) Avoid coadministration of gemtuzumab 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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) Monitor ECG and electrolytes if amisulpride is coadministered with gemtuzumab due to the potential for additive QT prolongation. Amisulpride causes dose- and concentration- dependent QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Use gemtuzumab ozogamicin and clarithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Use gemtuzumab ozogamicin and anagrelide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab ozogamicin and as needed during treatment. Additionally, monitor patients for cardiovascular effects during concomitant therapy and evaluate as necessary. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Use gemtuzumab ozogamicin and apomorphine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) Avoid coadministration of gemtuzumab 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Artemether; Lumefantrine: (Major) Avoid coadministration of gemtuzumab 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Artemether; lumefantrine is also associated with QT interval prolongation.
Asenapine: (Major) Avoid coadministration of gemtuzumab 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Asenapine has been associated with QT prolongation.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azithromycin: (Major) Avoid coadministration of azithromycin with gemtuzumab 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. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Bedaquiline: (Major) Use gemtuzumab ozogamicin and bedaquiline together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, 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). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Bedaquiline has been reported to prolong the QT interval. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Buprenorphine: (Major) Use gemtuzumab ozogamicin and buprenorphine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
Buprenorphine; Naloxone: (Major) Use gemtuzumab ozogamicin and buprenorphine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Buprenorphine has been associated with QT prolongation and has a possible risk of TdP.
Cabotegravir; Rilpivirine: (Moderate) Use gemtuzumab ozogamicin and rilpivirine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Ceritinib: (Major) Avoid coadministration of ceritinib with gemtuzumab if possible due to the risk of QT prolongation. If concomitant use is unavoidable, obtain an ECG and serum electrolytes prior to starting concomitant therapy and periodically monitor ECGs and electrolytes during therapy; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Chloroquine: (Major) Avoid coadministration of chloroquine with gemtuzumab 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Chlorpromazine: (Major) Use gemtuzumab ozogamicin and chlorpromazine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Concomitant use of ciprofloxacin and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Coadministration of gemtuzumab ozogamicin with cisapride is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride.
Citalopram: (Major) Avoid coadministration of gemtuzumab 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 prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Citalopram causes dose-dependent QT interval prolongation.
Clarithromycin: (Major) Use gemtuzumab ozogamicin and clarithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Clofazimine: (Moderate) Concomitant use of clofazimine and gemtuzumab may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clozapine: (Moderate) Use gemtuzumab ozogamicin and clozapine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Crizotinib: (Major) Avoid coadministration of crizotinib with gemtuzumab due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes at baseline and during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Dasatinib: (Moderate) Use gemtuzumab ozogamicin and dasatinib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving gemtuzumab ozogamicin and degarelix together as concurrent use may increase the risk of QT prolongation. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desflurane: (Major) Use gemtuzumab ozogamicin and halogenated anesthetics together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Halogenated anesthetics can prolong the QT interval.
Deutetrabenazine: (Moderate) Use gemtuzumab ozogamicin and deutetrabenazine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Concomitant use of dexmedetomidine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Major) Use gemtuzumab ozogamicin and quinidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinidine administration is also associated with QT prolongation and TdP.
Disopyramide: (Major) Use gemtuzumab ozogamicin and disopyramide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Disopyramide administration is associated with QT prolongation and TdP.
Dofetilide: (Major) Coadministration of dofetilide and gemtuzumab is not recommended as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with gemtuzumab as concurrent use may increase the risk of QT prolongation. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Use gemtuzumab ozogamicin and rilpivirine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use gemtuzumab ozogamicin and donepezil together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Moderate) Use gemtuzumab ozogamicin and donepezil together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Dronedarone: (Contraindicated) Coadministration of gemtuzumab ozogamicin with dronedarone is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds (msec) at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 msec 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 gemtuzumab 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 and as needed during treatment. Additionally, initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. 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) Use gemtuzumab ozogamicin and efavirenz together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. QTc prolongation has been observed with the use of efavirenz. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Use gemtuzumab ozogamicin and efavirenz together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. QTc prolongation has been observed with the use of efavirenz. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Use gemtuzumab ozogamicin and efavirenz together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. QTc prolongation has been observed with the use of efavirenz. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Eliglustat: (Major) Use gemtuzumab ozogamicin and eliglustat together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use gemtuzumab ozogamicin and rilpivirine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use gemtuzumab ozogamicin and rilpivirine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and gemtuzumab due to QT prolongation. If these agents must be used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Entrectinib: (Major) Avoid coadministration of entrectinib with gemtuzumab due to the risk of QT prolongation. If coadministration is necessary, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Entrectinib has been associated with QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Eribulin: (Major) Use gemtuzumab ozogamicin and eribulin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Eribulin has been associated with QT prolongation.
Erythromycin: (Major) Use gemtuzumab ozogamicin and erythromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Cases ofTdP have been spontaneously reported during postmarketing surveillance in patients receiving erythromycin. Fatalities have been reported.
Escitalopram: (Moderate) Concomitant use of escitalopram and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fingolimod: (Moderate) Use gemtuzumab ozogamicin and fingolimod together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. 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) Use gemtuzumab ozogamicin and flecainide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Concomitant use of fluconazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Coadministration of gemtuzumab ozogamicin with fluphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Fluphenazine is also associated with a possible risk for QT prolongation.
Fluvoxamine: (Moderate) Use gemtuzumab ozogamicin and fluvoxamine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation and torsade de pointes (TdP) have been reported during fluvoxamine post-marketing use.
Foscarnet: (Major) Avoid coadministration of gemtuzumab 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 gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Both QT prolongation andTdP have been reported during postmarketing use of foscarnet.
Fostemsavir: (Moderate) Use gemtuzumab ozogamicin and fostemsavir together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Use gemtuzumab ozogamicin and gemifloxacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Use gemtuzumab ozogamicin and gilteritinib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Gilteritinib has been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with gemtuzumab ozogamicin due to the potential for additive QT prolongation. If coadministration cannot be avoided, obtain an ECG and serum electrolytes prior to the start of gemtuzumab. Increase the frequency of ECG monitoring during coadministration and monitor serum electrolytes as needed. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Goserelin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and goserelin due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Granisetron: (Moderate) Use gemtuzumab ozogamicin and granisetron together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Granisetron has been associated with QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Halogenated Anesthetics: (Major) Use gemtuzumab ozogamicin and halogenated anesthetics together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Halogenated anesthetics can prolong the QT interval.
Haloperidol: (Moderate) Use gemtuzumab ozogamicin and haloperidol together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and histrelin due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Hydroxychloroquine: (Major) Avoid coadministration of gemtuzumab and hydroxychloroquine due to the risk of increased 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. Hydroxychloroquine prolongs the QT interval. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) Use gemtuzumab ozogamicin and ibutilide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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 gemtuzumab ozogamicin with iloperidone 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Iloperidone has been associated with QT prolongation.
Isoflurane: (Major) Use gemtuzumab ozogamicin and halogenated anesthetics together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Halogenated anesthetics can prolong the QT interval.
Itraconazole: (Moderate) Use gemtuzumab ozogamicin and itraconazole together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Itraconazole has been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with gemtuzumab 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and gemtuzumab due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Use gemtuzumab ozogamicin and clarithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes at baseline and throughout treatment if coadministration of lapatinib with gemtuzumab is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Lefamulin: (Major) Avoid coadministration of lefamulin with gemtuzumab as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG and electrolytes prior to 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with gemtuzumab due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Leuprolide: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and leuprolide due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Leuprolide; Norethindrone: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and leuprolide due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and gemtuzumab due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lithium: (Moderate) Concomitant use of lithium and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Moderate) Monitor ECG and electrolytes if lofexidine is coadministered with gemtuzumab due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Loperamide: (Moderate) Use gemtuzumab ozogamicin and loperamide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Loperamide; Simethicone: (Moderate) Use gemtuzumab ozogamicin and loperamide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with gemtuzumab 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. Lopinavir is associated with QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as gemtuzumab. 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Maprotiline: (Major) Use gemtuzumab ozogamicin and maprotiline together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Use gemtuzumab ozogamicin and mefloquine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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.
Methadone: (Major) Use gemtuzumab ozogamicin and methadone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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: (Moderate) Concomitant use of metronidazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) Use gemtuzumab ozogamicin and midostaurin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation has been reported in patients who received midostaurin in clinical trials.
Mifepristone: (Moderate) Concomitant use of mifepristone and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mobocertinib: (Major) Concomitant use of mobocertinib and gemtuzumab 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) Use gemtuzumab ozogamicin and moxifloxacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinolones have been associated with a risk of QT prolongation andTdP. TdP has been reported during postmarketing surveillance of moxifloxacin.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and gemtuzumab ozogamicin; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Use gemtuzumab ozogamicin and olanzapine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of fluoxetine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Use gemtuzumab ozogamicin and olanzapine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Moderate) Use gemtuzumab ozogamicin and olanzapine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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 gemtuzumab 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. 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: (Moderate) Monitor ECG and electrolytes if osilodrostat is coadministered with gemtuzumab due to the potential for additive QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid coadministration of gemtuzumab with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, obtain an ECG and serum electrolytes prior to the start of combination therapy, and periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Oxaliplatin: (Major) Obtain a baseline ECG and electrolyte panel if coadministration of gemtuzumab ozogamicin with oxaliplatin is necessary; monitor ECGs for QT prolongation and monitor electrolytes during therapy. Correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking gemtuzumab due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed durin

g treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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 gemtuzumab 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 gemtuzumab ozogamicin with paliperidone 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 and as needed during treatment. Close monitoring is particularly essential for patients with known risk factors for cardiac disease or arrhythmias. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose.
Panobinostat: (Major) Avoid coadministration of gemtuzumab ozogamicin with panobinostat 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. QT prolongation has been reported with panobinostat.
Pasireotide: (Moderate) Use gemtuzumab ozogamicin and pasireotide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) Avoid coadministration of gemtuzumab ozogamicin with pazopanib 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Pazopanib has been reported to prolong the QT interval.
Pentamidine: (Major) Use gemtuzumab ozogamicin and pentamidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Systemic pentamidine has also been associated with QT prolongation.
Perphenazine: (Minor) Coadministration of gemtuzumab ozogamicin with perphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Perphenazine is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Coadministration of gemtuzumab ozogamicin with perphenazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Perphenazine is associated with a possible risk for QT prolongation.
Pimavanserin: (Major) Avoid coadministration of gemtuzumab ozogamicin with pimavanserin 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Pimavanserin may cause QT prolongation.
Pimozide: (Contraindicated) Coadministration of gemtuzumab ozogamicin with pimozide is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Pimozide is associated with a well-established risk of QT prolongation and TdP.
Pitolisant: (Major) Avoid coadministration of pitolisant with gemtuzumab ozogamicin as concurrent use may increase the risk of QT prolongation. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Pitolisant prolongs the QT interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking gemtuzumab 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 treatment initiation is considered, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment; monitor for signs and symptoms of infection. 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Posaconazole: (Moderate) Use posaconazole with caution in combination with gemtuzumab as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Primaquine: (Moderate) Use gemtuzumab ozogamicin and primaquine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Primaquine may prolong the QT interval.
Procainamide: (Major) Use gemtuzumab ozogamicin and procainamide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) Coadministration of gemtuzumab ozogamicin with prochlorperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Prochlorperazine is associated with a possible risk for QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of propafenone and gemtuzumab 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.
Quetiapine: (Major) Concomitant use of quetiapine and gemtuzumab 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.
Quinidine: (Major) Use gemtuzumab ozogamicin and quinidine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Quinidine administration is also associated with QT prolongation and TdP.
Quinine: (Major) Avoid coadministration of gemtuzumab ozogamicin with quinine 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Quinine has been associated with QT prolongation and rare cases of TdP.
Quizartinib: (Major) Concomitant use of quizartinib and gemtuzumab 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: (Moderate) Use gemtuzumab ozogamicin and ranolazine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Relugolix: (Moderate) Use gemtuzumab ozogamicin and relugolix together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use gemtuzumab ozogamicin and relugolix together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Ribociclib: (Major) Avoid coadministration of gemtuzumab ozogamicin with ribociclib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Prolongation of the QT has not been reported with gemtuzumab ozogamicin, but it has been reported with other drugs that contain calicheamicin.
Ribociclib; Letrozole: (Major) Avoid coadministration of gemtuzumab ozogamicin with ribociclib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Prolongation of the QT has not been reported with gemtuzumab ozogamicin, but it has been reported with other drugs that contain calicheamicin.
Rilpivirine: (Moderate) Use gemtuzumab ozogamicin and rilpivirine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Moderate) Use gemtuzumab ozogamicin and risperidone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Romidepsin: (Moderate) Use gemtuzumab ozogamicin and romidepsin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Romidepsin has also been reported to prolong the QT interval.
Saquinavir: (Major) Avoid coadministration of gemtuzumab ozogamicin with saquinavir 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. 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) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with gemtuzumab is necessary due to the risk of additive QT prolongation. Additionally, obtain serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Sertraline: (Moderate) Concomitant use of sertraline and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. 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) Use gemtuzumab ozogamicin and halogenated anesthetics together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Halogenated anesthetics can prolong the QT interval.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving gemtuzumab due to the potential for 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and gemtuzumab may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Use gemtuzumab ozogamicin and solifenacin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. 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 gemtuzumab 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. Sorafenib is associated with QTc prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Sotalol: (Major) Concomitant use of sotalol and gemtuzumab 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.
Sunitinib: (Moderate) Use gemtuzumab ozogamicin and sunitinib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Use gemtuzumab ozogamicin and tacrolimus together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Tacrolimus may cause QT prolongation.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telavancin: (Moderate) Use gemtuzumab ozogamicin and telavancin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Telavancin has been associated with QT prolongation.
Tetrabenazine: (Major) Avoid coadministration of gemtuzumab ozogamicin with tetrabenazine 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Tetrabenazine causes a small increase in the corrected QT interval.
Thioridazine: (Contraindicated) Coadministration of gemtuzumab ozogamicin with thioridazine is contraindicated due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Thioridazine is associated with a well-established risk of QT prolongation and TdP.
Tolterodine: (Moderate) Use gemtuzumab ozogamicin and tolterodine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of gemtuzumab ozogamicin with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, obtain an ECG and serum electrolytes prior to starting therapy and closely monitor during treatment; correct hypokalemia or hypomagnesemia. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Trazodone: (Major) Concomitant use of trazodone and gemtuzumab 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.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and gemtuzumab may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Coadministration of gemtuzumab ozogamicin with trifluoperazine may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Trifluoperazine is associated with a possible risk for QT prolongation.
Triptorelin: (Moderate) Obtain an ECG and serum electrolytes prior to initiation of concomitant use of gemtuzumab ozogamicin and triptorelin due to the potential for additive QT prolongation and the risk of torsade de pointes (TdP); monitor ECGs and electrolytes as needed during treatment. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
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 gemtuzumab due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, obtain a baseline ECG and electrolyte panel. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Vardenafil: (Moderate) Concomitant use of vardenafil and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Use gemtuzumab ozogamicin and vemurafenib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Vemurafenib has been associated with QT prolongation.
Venlafaxine: (Major) Concomitant use of venlafaxine and gemtuzumab 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.
Voclosporin: (Moderate) Concomitant use of voclosporin and gemtuzumab may increase the risk of QT prolongation. If concomitant use is necessary and to minimize the risk of progression to TdP, monitor ECG and correct electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Use gemtuzumab ozogamicin and clarithromycin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Moderate) Use gemtuzumab ozogamicin and voriconazole together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Voriconazole has been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Moderate) Use gemtuzumab ozogamicin and vorinostat together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Vorinostat therapy is associated with a risk of QT prolongation.
Ziprasidone: (Major) Avoid coadministration of gemtuzumab ozogamicin with ziprasidone 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 and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab ozogamicin, it has been reported with other drugs that contain calicheamicin. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors.

Mylotarg Intravenous Inj Pwd F/Sol: 4.5mg

Adults

Newly diagnosed AML, single agent: induction therapy, 6 mg/m2 IV; consolidation, 2 mg/m2 IV.Newly diagnosed AML, combination therapy: induction and consolidation therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).Relapsed or refractory AML, single agent: induction therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).

Geriatric

Newly diagnosed AML, single agent: induction therapy, 6 mg/m2 IV; consolidation, 2 mg/m2 IV.Newly diagnosed AML, combination therapy: induction and consolidation therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).Relapsed or refractory AML, single agent: induction therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).

Adolescents

Newly diagnosed AML, single agent: Safety and efficacy not established.Newly diagnosed AML, multi-agent chemotherapy: 3 mg/m2 IV.Relapsed or refractory AML, single agent: induction therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).

Children

2 years and older
Newly diagnosed AML, single agent: Safety and efficacy not established.Newly diagnosed AML, multi-agent chemotherapy: 3 mg/m2 IV (body surface area (BSA) of 0.6 m2 or greater) OR 0.1 mg/kg IV (BSA less than 0.6 m2).Relapsed or refractory AML, single agent: induction therapy, 3 mg/m2 IV (maximum dose of 4.5 mg).
Less than 2 years
Newly diagnosed AML, single agent: Safety and efficacy not established.Newly diagnosed AML, multi-agent chemotherapy: 3 mg/m2 IV (body surface area (BSA) of 0.6 m2 or greater) OR 0.1 mg/kg IV (BSA less than 0.6 m2).Relapsed or refractory AML, single agent: Safety and efficacy not established.

Infants

Newly diagnosed AML, single agent: Safety and efficacy not established.Newly diagnosed AML, multi-agent chemotherapy: 0.1 mg/kg IV.Relapsed or refractory AML, single agent: Safety and efficacy not established.

Gemtuzumab ozogamicin is a CD33-directed antibody-drug conjugate. CD33 is expressed on myeloid cells. Gemtuzumab ozogamicin consists of a cytotoxic agent, N-acetyl-gamma-calicheamicin, covalently linked to a recombinant humanized anti-CD33 IgG4 kappa monoclonal antibody. N-acetyl-gamma-calicheamicin induces double-strand DNA breaks resulting in cell cycle arrest and apoptotic cell death. Gemtuzumab ozogamicin binds to CD33-expressing tumor cells where it becomes internalized and N-acetyl-gamma-calicheamicin dimethyl hydrazide is released via hydrolytic cleavage of the link.

Gemtuzumab ozogamicin is administered intravenously. The volume of distribution of the monoclonal antibody is approximately 21.4 L. N-acetyl-gamma-calicheamicin dimethyl hydrazide is about 97% bound to human plasma proteins in vitro. Following gemtuzumab ozogamicin 9 mg/m2 IV every 14 days for 2 doses, the clearance was 0.35 L/hour after the first dose and 0.15 L/hour after the second dose. The terminal half-life was 62 hours after the first dose and 90 hours after the second dose. N-acetyl-gamma- calicheamicin dimethyl hydrazide is metabolized by nonenzymatic reduction in vitro.
In studies, near maximal peripheral CD33 saturation occurred following gemtuzumab ozogamicin dosing at dose levels of 2 mg/m2 and above. Saturation of a high percentage of CD33 antigenic sites may be required for maximum delivery of calicheamicin to leukemic blast cells.
Affected cytochrome P450 isoenzymes and transporters: none At clinically relevant concentrations, it does not appear that gemtuzumab ozogamicin inhibits CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5. Additionally, N-acetyl-gamma-calicheamicin dimethyl hydrazide 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-glycoprotein, 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.

Intravenous Route

Following gemtuzumab ozogamicin 9 mg/m2 IV every 14 days for 2 doses, the Cmax values were 3 mg/L and 3.6 mg/L for the first and second doses, respectively.

Pregnancy

Gemtuzumab 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 gemtuzumab ozogamicin. Discuss the potential hazard to the fetus if gemtuzumab ozogamicin is used during pregnancy or if a patient becomes pregnant while taking this drug. Embryo-fetal toxicities including fetal growth retardation, delayed skeletal ossification, digital malformations, absence of the aortic arch, anomalies in the long bones in the forelimbs, misshapen scapula, absence of a vertebral centrum, and fused sternebrae were observed when gemtuzumab ozogamicin was administered to pregnant rats during organogenesis at doses resulting in exposures of 0.4-times or greater the exposure in humans (at the maximum recommended dose).

It is not known if gemtuzumab ozogamicin or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because of the potential for adverse reactions in nursing infants, women should discontinue breast-feeding during gemtuzumab ozogamicin therapy and for at least 1 month after the last dose.