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    Miscellaneous Monoclonal Antibodies that Target Cell Surface Receptors

    BOXED WARNING

    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.

    DEA CLASS

    Rx

    DESCRIPTION

    A CD33-directed antibody-drug conjugate
    Used in adults 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

    COMMON BRAND NAMES

    Mylotarg

    HOW SUPPLIED

    Mylotarg Intravenous Inj Pwd F/Sol: 4.5mg

    DOSAGE & INDICATIONS

    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 III 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 III 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 II 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 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.

    MAXIMUM DOSAGE

    Adults

    Newly diagnosed AML, single agent: 6 mg/m2 IV on day 1 and 3 mg/m2 IV on day 8 as induction therapy, then 2 mg/m2 on day 1 repeated every 4 weeks for up to 8 cycles.
    Newly diagnosed AML, combination therapy: 3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy, 3 mg/m2 on day 1 (maximum dose of 4.5 mg) for 2 cycles of consolidation therapy.
    Relapsed or refractory AML, single agent: 3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy.

    Geriatric

    Newly diagnosed AML, single agent: 6 mg/m2 IV on day 1 and 3 mg/m2 IV on day 8 as induction therapy, then 2 mg/m2 on day 1 repeated every 4 weeks for up to 8 cycles.
    Newly diagnosed AML, combination therapy: 3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy, 3 mg/m2 on day 1 (maximum dose of 4.5 mg) for 2 cycles of consolidation therapy.
    Relapsed or refractory AML, single agent: 3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy.

    Adolescents

    3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy.

    Children

    2 years and older: 3 mg/m2 (maximum dose of 4.5 mg) IV on days 1, 4, and 7 as induction therapy.
    Less than 2 years: Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    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.

    ADMINISTRATION

     
    CAUTION: Observe and exercise appropriate precautions for handling, preparing, and administering antineoplastic therapy.

    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.

    STORAGE

    Mylotarg:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Gemtuzumab ozogamicin hypersensitivity, infusion-related reactions

    Hypersensitivity reactions including anaphylaxis and infusion-related reactions have been reported with gemtuzumab ozogamicin therapy; life-threatening or fatal infusion-related reaction may occur during or within 24 hours of the infusion. Discontinue gemtuzumab ozogamicin in patients who develop anaphylaxis (e.g., severe respiratory symptoms or clinically significant hypotension) and/or severe or life-threatening infusion-related reaction. Use is contraindicated in patients with a gemtuzumab ozogamicin hypersensitivity or a history of hypersensitivity to any of its components or to any of the excipients. Premedicate patients with acetaminophen, diphenhydramine, and a corticosteroid prior to each infusion. Monitor patients for signs and symptoms of infusion-related reactions (e.g., fever, chills, hypotension, tachycardia, hypoxia and respiratory failure) during and for at least 1 hour after the end of the infusion or until signs and symptoms completely resolve; monitor vital signs frequently during the infusion. If a patient experiences an infusion-related reaction, interrupt the infusion and start appropriate medical management including supportive care measures as indicated. Additional doses of acetaminophen, diphenhydramine, and a corticosteroid may be given.

    Bleeding, bone marrow suppression, neutropenia, thrombocytopenia

    Severe myelosuppression/bone marrow suppression including prolonged neutropenia and thrombocytopenia has been reported in patients who received gemtuzumab ozogamicin in combination with cytarabine and daunorubicin. In all patients who receive gemtuzumab ozogamicin, monitor complete blood counts prior to each dose and at least 3 times per week until resolution of cytopenias. Serious bleeding has also occurred in patients who received gemtuzumab ozogamicin; some cases were fatal. Monitor for signs and symptoms of bleeding during therapy. A dose delay or permanent therapy discontinuation may be necessary in patients who develop severe bleeding or persistent thrombocytopenia. Provide appropriate supportive care if bleeding occurs.

    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.

    Tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) may occur with gemtuzumab ozogamicin therapy. Institute prophylactic measures to prevent TLS. Monitor patients for signs or symptoms of TLS and treat as clinically appropriate.

    Alcoholism, diabetes mellitus, females, malnutrition, QT prolongation, thyroid disease

    QT prolongation has been reported with other drugs that contain calicheamicin, such as gemtuzumab ozogamicin. The risk of QT prolongation may be higher in patients with a history of or predisposition for QT prolongation, patients who are taking other drugs known to prolong QT interval, and patients who have pre-existing electrolyte imbalances. Therefore, obtain an electrocardiogram (ECG) and monitor serum electrolytes prior to the start of treatment and periodically during therapy as clinically indicated in these patients. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, hepatic dysfunction, or patients who have received high-cumulative dose anthracycline therapy may also be at increased risk for QT prolongation.

    Geriatric, infection

    Geriatric patients with relapsed or refractory acute myelogenous leukemia had a higher incidence of fever and severe infection compared with patients aged less than 65 years following treatment with single-agent gemtuzumab ozogamicin in a clinical study.

    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).

    Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during gemtuzumab ozogamicin treatment. Pregnancy testing prior to starting gemtuzumab ozogamicin therapy is recommended for females of reproductive potential. These patients should avoid pregnancy and use effective contraception during therapy and for at least 6 months after the last gemtuzumab ozogamicin dose. Due to the risk of male-mediated teratogenicity, men with female partners of reproductive potential should avoid fathering a child and use effective contraception during and for at least 3 months after gemtuzumab ozogamicin therapy. Based on information from animal studies, infertility may occur in females or males of reproductive potential.

    Breast-feeding

    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.

    ADVERSE REACTIONS

    Severe

    infection / Delayed / 0-55.0
    hepatotoxicity / Delayed / 0-51.0
    hyponatremia / Delayed / 0-44.0
    cardiotoxicity / Delayed / 0-28.0
    bleeding / Early / 7.0-21.0
    fever / Early / 0-16.0
    elevated hepatic enzymes / Delayed / 0-14.0
    fatigue / Early / 0-12.0
    rash / Early / 0-11.0
    hyperbilirubinemia / Delayed / 0-8.0
    nephrotoxicity / Delayed / 0-6.0
    oral ulceration / Delayed / 0-4.0
    subdural hematoma / Early / 0-3.0
    intracranial bleeding / Delayed / 0-3.0
    headache / Early / 0-2.0
    sinusoidal obstruction syndrome (SOS) / Delayed / 0-2.0
    veno-occlusive disease (VOD) / Delayed / 0-2.0
    diarrhea / 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
    hypoxia / Early / Incidence not known
    infusion-related reactions / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known

    Mild

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

    DRUG INTERACTIONS

    Aclidinium; Formoterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Amitriptyline: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amitriptyline; Chlordiazepoxide: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amoxicillin; Clarithromycin; Lansoprazole: (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.
    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 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, 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 (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 indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines.
    Arformoterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Moderate) Use gemtuzumab ozogamicin and aripiprazole 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 during therapeutic use of aripiprazole and following overdose.
    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) Use gemtuzumab ozogamicin and atomoxetine 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 during therapeutic use of atomoxetine and following overdose.
    Azithromycin: (Moderate) Use gemtuzumab ozogamicin and azithromycin 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 TdP have been spontaneously reported during azithromycin postmarketing surveillance.
    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) Use gemtuzumab ozogamicin and metronidazole 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. Potential QT prolongation has been reported in case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Use gemtuzumab ozogamicin and metronidazole 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. Potential QT prolongation has been reported in case reports with metronidazole.
    Budesonide; Formoterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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) Use gemtuzumab ozogamicin and chloroquine 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. Chloroquine is associated with an increased risk of QT prolongation and TdP; fatalities have been reported. The risk of QT prolongation is increased with higher chloroquine doses.
    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.
    Ciprofloxacin: (Moderate) Use gemtuzumab ozogamicin and ciprofloxacin 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. Rare cases of QT prolongation and TdP have been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Severe) 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: (Major) Monitor ECG and electrolytes if clofazimine is coadministered with gemtuzumab due to the potential for additive QT prolongation. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
    Clomipramine: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    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) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Codeine; Promethazine: (Moderate) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    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 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.
    Desipramine: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Deutetrabenazine: (Moderate) If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. For patients taking a deutetrabenazine dosage more than 24 mg/day with gemtuzumab, assess the QTc interval before and after increasing the dosage of either medication. Use gemtuzumab ozogamicin and deutetrabenazine together with caution 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, it has been reported with other drugs that contain calicheamicin. Clinically relevant QT prolongation may occur with deutetrabenazine.
    Dextromethorphan; Promethazine: (Moderate) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    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.
    Doxepin: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Dronedarone: (Severe) 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: (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.
    Enflurane: (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.
    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.
    Erythromycin; Sulfisoxazole: (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) Use gemtuzumab ozogamicin and escitalopram 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. Escitalopram has been associated with a risk of QT prolongation and TdP.
    Ezogabine: (Moderate) Use gemtuzumab ozogamicin and ezogabine 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. Ezogabine has been associated with QT prolongation.
    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) Use gemtuzumab ozogamicin and fluconazole 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. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Fluoxetine: (Moderate) Use gemtuzumab ozogamicin and fluoxetine 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 TdP have been reported in patients treated with fluoxetine.
    Fluoxetine; Olanzapine: (Moderate) Use gemtuzumab ozogamicin and fluoxetine 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 TdP have been reported in patients treated with fluoxetine. (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.
    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.
    Fluticasone; Salmeterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Formoterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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.
    Glycopyrrolate; Formoterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Halothane: (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.
    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 ozogamicin with hydroxychloroquine 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. Hydroxychloroquine may cause QT interval prolongation.
    Hydroxyzine: (Moderate) Use gemtuzumab ozogamicin and hydroxyzine 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. Postmarketing data indicate that hydroxyzine causes QT prolongation and 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.
    Imipramine: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Indacaterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (Major) Use gemtuzumab ozogamicin and ketoconazole 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. Ketoconazole has been associated with prolongation of the QT interval.
    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.
    Levalbuterol: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levofloxacin: (Moderate) Use gemtuzumab ozogamicin and levofloxacin 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. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Lithium: (Moderate) Use gemtuzumab ozogamicin and lithium 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. Lithium has been associated with QT prolongation.
    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.
    Long-acting beta-agonists: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Use gemtuzumab ozogamicin and lopinavir; ritonavir 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. Lopinavir; ritonavir is associated with QT prolongation.
    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.
    Meperidine; Promethazine: (Moderate) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Metaproterenol: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Use gemtuzumab ozogamicin and metronidazole 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. Potential QT prolongation has been reported in case reports with metronidazole.
    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) Use gemtuzumab ozogamicin and mifepristone 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. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Mifepristone has been associated with dose-dependent prolongation of the QT interval.
    Mirtazapine: (Moderate) Use gemtuzumab ozogamicin and mirtazapine 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. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. TdP has also been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation.
    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.
    Nortriptyline: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Octreotide: (Moderate) Use gemtuzumab ozogamicin and octreotide 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. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Use gemtuzumab ozogamicin and ofloxacin 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 and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    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.
    Olodaterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ondansetron: (Major) Use gemtuzumab ozogamicin and ondansetron 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. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of TdP.
    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.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    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.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    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. (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Phenylephrine; Promethazine: (Moderate) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also 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: (Severe) 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.
    Pirbuterol: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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) Use gemtuzumab ozogamicin and promethazine 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. Promethazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
    Propafenone: (Major) Use gemtuzumab ozogamicin and propafenone 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. Propafenone is a class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
    Protriptyline: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Quetiapine: (Major) Avoid coadministration of gemtuzumab ozogamicin with quetiapine 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. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
    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.
    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.
    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.
    Salmeterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Sertraline: (Moderate) Use gemtuzumab ozogamicin and sertraline 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. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    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.
    Short-acting beta-agonists: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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) Monitor ECGs for QT prolongation and monitor electrolytes at baseline and during treatment if coadministration of sorafenib with gemtuzumab is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib 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.
    Sotalol: (Major) Use gemtuzumab ozogamicin and sotalol 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. Sotalol administration is also associated with QT prolongation and TdP. Proarrhythmic events should be anticipated after initiation of sotalol and after each upward dosage adjustment.
    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) Use gemtuzumab ozogamicin and tamoxifen 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. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    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.
    Telithromycin: (Moderate) Use gemtuzumab ozogamicin and telithromycin 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. Telithromycin is also associated with QT prolongation and TdP.
    Terbutaline: (Minor) Coadministration of gemtuzumab ozogamicin with short-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (Severe) 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.
    Tiotropium; Olodaterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Avoid coadministration of gemtuzumab ozogamicin with trazodone 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. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP.
    Tricyclic antidepressants: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    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.
    Trimipramine: (Minor) Use gemtuzumab ozogamicin and tricyclic antidepressants 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. TCAs share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    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.
    Umeclidinium; Vilanterol: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists 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. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Use gemtuzumab ozogamicin and vardenafil 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. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    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) Use gemtuzumab ozogamicin and venlafaxine 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. Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has also been reported with postmarketing use.
    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.

    PREGNANCY AND LACTATION

    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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.
    Pharmacodynamics: 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/mL and 3.6 mg/mL for the first and second doses, respectively.