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    Anthracyclines

    BOXED WARNING

    Bone marrow suppression, herpes infection, infection, neutropenia, requires a specialized care setting, requires an experienced clinician, thrombocytopenia, varicella, viral infection

    Severe bone marrow suppression is a relative contraindication to idarubicin depending upon the etiology of the suppression. Patients with acute leukemia may require treatment with idarubicin despite severe bone marrow suppression. Idarubicin should be used cautiously in patients with bone marrow suppression, coagulopathy, or in those who have received previous myelosuppressive therapy such as chemotherapy or radiotherapy. Therefore, this drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy. Administration of idarubicin requires a specialized care setting such as a hospital or treatment facility. Patients with preexisting marrow suppression, including neutropenia and/or thrombocytopenia, should be allowed to recover their counts prior to idarubicin administration. Patients should be treated for any active infection prior to receiving idarubicin. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

    Extravasation, intramuscular administration, subcutaneous administration

    Idarubicin is a vesicant. Extravasations of idarubicin infusions should be avoided. Patients should be closely monitored during IV infusions for signs and symptoms of extravasation such as poor blood return, pain and swelling. If extravasation occurs, stop the infusion and remove the tubing. Attempt to aspirate the drug prior to removing the needle. Elevate the affected area and treat with ice packs. As this can be a progressive injury, appropriate long-term follow-up is required. Intramuscular administration and subcutaneous administration of idarubicin should be avoided due to severe skin and tissue necrosis which may occur.

    Hepatic disease, jaundice

    Idarubicin should be used cautiously in patients with hepatic disease and/or jaundice. Since hepatic impairment can affect the disposition of idarubicin, liver function should be evaluated using serum bilirubin as an indicator prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if bilirubin serum levels exceeded 2 mg%. However, in one Phase III trial, patients with bilirubin levels between 2.6 and 5 mg% received the anthracycline with a 50% reduction in dose. Dose reduction of idarubicin should be considered if the bilirubin levels are above the normal range (see Dosage).

    Renal impairment

    Doses of idarubicin should be adjusted for severe renal impairment or renal failure, although specific guidelines are not available and < 5% of the dose is eliminated renally. Kidney function should be evaluated with serum creatinine as an indicator prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if creatinine serum levels exceeded 2 mg%. Dose reduction of idarubicin should be considered if the creatinine levels are above the normal range.

    Acute myocardial infarction, alcoholism, angina, bradycardia, cardiac arrhythmias, cardiac disease, cardiotoxicity, children, coronary artery disease, diabetes mellitus, females, geriatric, heart failure, hypertension, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, maximum cumulative lifetime dose, myocardial infarction, QT prolongation, radiation therapy, thyroid disease, ventricular dysfunction

    Idarubicin is a cardiotoxin and can cause congestive heart failure due to its effects on cardiac myofibrils. Patients with preexisting cardiac disease including heart failure, angina, left ventricular dysfunction (i.e., ejection fraction < 50%), recent or acute myocardial infarction, or cardiac arrhythmias are not good candidates to receive idarubicin. Angina and arrhythmias are relative contraindications to idarubicin therapy, depending on the degree of clinical impairment. Although it is suggested that idarubicin causes less cardiotoxicity than other agents in its class, patients should be observed closely for signs of cardiotoxicity if idarubicin is given. The risk of cardiac toxicity may be higher in children < 2 years or geriatric patients > 60 years of age, patients who have received prior anthracycline therapy, and those who are receiving or have received radiation therapy to the mediastinal-pericardial area. Patients > 60 years of age undergoing induction therapy with idarubicin experienced an increased incidence of cardiac effects vs. younger patients. Females and children may be more sensitive to the cardiotoxic effects of anthracyclines. Children treated with anthracyclines may develop late cardiotoxicity. Due to the risk of long-term cardiotoxicity, it has been recommended that children treated with anthracyclines should undergo screening with ECGs and echocardiograms every 2 years and 24-hour continuous ECGs and radionuclide angiograms every 5 years. Generally, patients with a left ventricular ejection fraction < 50% are not considered candidates for anthracycline therapy; the risks vs. benefits of anthracycline therapy must be carefully considered in these patients. Patients should be observed closely for signs of idarubicin-induced cardiotoxicity; early recognition is essential for successful treatment. Establishment of baseline left ventricular function and periodic monitoring are recommended. Patients currently receiving idarubicin should wait at least 4 weeks following the last dose before undergoing periodic cardiac evaluation to allow cardiac function to return to baseline. Although the most definitive technique for assessing anthracycline-induced cardiotoxicity is endomyocardial biopsy, echocardiograms or serial gated cardiography (MUGA) scans may also indicate if a patient is developing cardiotoxicity. A left ventricular ejection fraction < 50% or an absolute decrease of 10—20% in left ventricular heart function are indications to discontinue anthracycline therapy. Cardiotoxicity is dose related; although there is little data, the maximum cumulative lifetime dose of idarubicin is suggested to be 150 mg/m2 IV, and should only be exceeded with extreme caution. Use idarubicin with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation.

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic anthracycline; analog of daunorubicin; less cardiotoxicity and may produce more aplasia and mucositis with repeated use than other anthracyclines; oral form under investigation.

    COMMON BRAND NAMES

    Idamycin PFS

    HOW SUPPLIED

    Idamycin PFS/Idarubicin/Idarubicin Hydrochloride Intravenous Inj Sol: 1mg, 1mL

    DOSAGE & INDICATIONS

    For induction therapy or post-remission therapy in adults with acute myelogenous leukemia (AML) in combination with cytarabine, Ara-C.
    NOTE: Idarubicin has been designated an orphan drug by the FDA for this indication.
    Intravenous dosage
    Adults

    8—12 mg/m2 IV (over 10—15 minutes) once daily for 3 days in combination with cytarabine. If severe mucositis occurred following a course of therapy, allow mucositis to resolve and reduce the dose of the next course by 25%.

    Adolescents† and Children†

    10—12 mg/m2 IV (over 10—30 minutes) once daily for 3 days; repeat every 3 weeks. NOTE: These are general guidelines. Refer to individual protocols for exact dosage.

    For the treatment of acute promyelocytic leukemia (APL).
    For the treatment of APL, in combination with other approved antileukemic agents.
    Intravenous dosage
    Adults

    12 mg/m2 given as a slow IV injection over 10—15 minutes daily for 3 days in combination with cytarabine. A second course may be administered in patients who have evidence of leukemia after the first induction course. If severe mucositis occurred following the first course of therapy, allow mucositis to resolve and reduce the dose of the next course by 25%. Induction therapy may be followed by consolidation therapy; however, there is no consensus regarding the optimal regimen to be used for consolidation.

    For remission induction treatment in patients with newly diagnosed APL, in combination with tretinoin†.
    Intravenous dosage
    Adults <= 61 years

    12 mg/m2/dose IV on days 2, 4, 6, and 8 plus tretinoin 45 mg/m2/day PO in 2 divided doses until complete remission (CR) to a maximum of 45 or 90 days has been evaluated in 2 clinical trials (AIDA 0493 study; AIDA 2000 study). Adults less than 20 years of age received tretinoin 25 mg/m2/day PO in the AIDA 0493 study. Patients who achieved a hematologic CR received 3 anthracycline-containing consolidation therapy courses. Additionally, most patients in these studies who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy. Prophylactic use of corticosteroids was recommended during induction therapy to help prevent differentiation (retinoic acid) syndrome.

    Children and Adolescents

    12 mg/m2/dose IV on days 2, 4, 6, and 8 plus tretinoin 25 mg/m2/day PO in 2 divided doses until complete remission (CR) or a maximum of 90 days has been evaluated in a clinical trial (AIDA 0493 study). Patients who achieved a hematologic CR received 3 multi-agent chemotherapy consolidation courses containing anthracyclines and cytarabine. Additionally, most patients who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy. In a subgroup analysis of the AIDA 0493 study, induction therapy with tretinoin plus idarubicin resulted in a post-induction hematologic CR rate of 96% in 107 evaluable pediatric patients (median age, 11.6 years; range, 1.4—17.9 years). Tretinoin was administered for a median of 32 days (range, 1—56 days) during induction therapy. The 10-year event-free survival and overall survival rates were 76% and 89%, respectively. Retinoic acid syndrome was reported in 8 patients (definitely present, n = 2; indeterminate, n = 6) and pseudotumor cerebri developed in 10 patients. There were 4 deaths during induction therapy.

    For consolidation treatment following tretinoin and idarubicin induction therapy in patients with newly diagnosed APL, in combination with tretinoin-containing chemotherapy†.
    Intravenous dosage
    Adults <= 61 years

    Following induction therapy with tretinoin (45 mg/m2/day PO in 2 divided daily doses until complete remission (CR) or a maximum of 45 days) plus idarubicin (12 mg/m2/dose IV on days 2, 4, 6, and 8), patients who achieved a hematologic CR received 3 risk-adapted tretinoin- and anthracycline-based consolidation therapy courses in a clinical study (AIDA 2000 study). All patients in this study received tretinoin 45 mg/m2/day PO for 15 days starting on day 1 of each consolidation cycle. Patients with low- or intermediate–risk APL (defined as an initial white blood cell count < 10 X 109/L) received: idarubicin 5 mg/m2/dose IV on days 1—4 (course 1), mitoxantrone 10 mg/m2/dose IV on days 1—5 (course 2); and idarubicin 12 mg/m2/dose IV on day 1 (course 3). Patients with high–risk APL received: idarubicin 5 mg/m2/dose IV on days 1—4 and cytarabine 1000 mg/m2/day IV on days 1—4 (course 1); mitoxantrone 10 mg/m2/dose IV on days 1—5 and etoposide 100 mg/m2/dose IV on days 1—5 (course 2); and idarubicin 12 mg/m2/dose IV on day 1, cytarabine 150 mg/m2 subcutaneously every 8 hours on days 1—5, and 6-thioguanine 70 mg/m2 PO every 8 hours on days 1—5 (course 3). Intrathecal methotrexate 12 mg and methylprednisone 40 mg were administered prior to each consolidation course in patients with high-risk disease. Additionally, patients who achieved a molecular CR after consolidation received up to 2 years of tretinoin-containing maintenance therapy.

    For the treatment of acute lymphocytic leukemia (ALL)†.
     NOTE: Idarubicin has been designated an orphan drug by the FDA for ALL in pediatric patients.
    For the treatment of relapsed or refractory ALL, in combination with cytarabine†.
    Intravenous dosage
    Adults

    40 mg/m2 IV once on day 3 plus cytarabine 3 grams/m2 daily IV over 3 hours on days 1 to 5 (with granulocyte colony-stimulating factor starting on day 7 until neutrophil recovery) and idarubicin 5 mg/m2 daily IV for 6 days, cytarabine 1 gram/m2 daily IV over 6 hours for 6 days, and prednisone 40 mg/m2 daily for 21 days have been studied as induction therapy in patients with relapsed or refractory acute lymphocytic leukemia (ALL) in nonrandomized trials. In some responding patients, induction therapy was followed by multi-agent consolidation therapy and bone marrow transplantation (BMT) (in patients less than 55 years of age).

    Adolescents and Children

    40 mg/m2 IV once on day 3 and cytarabine 3 grams/m2 daily IV over 3 hours on days 1 to 5 plus prophylactic intrathecal methotrexate (dosed for age) on days 1 and 5 (with prednisone 0.5 mg/kg daily and glucocorticoid eye drops during therapy plus granulocyte colony-stimulating factor starting on day 7 until granulocyte recovery) and idarubicin 5 mg/m2 IV daily for 6 days, cytarabine 1 gram/m2 daily IV over 6 hours for 6 days, and prednisone 40 mg/m2 daily PO for 21 days have been studied as induction therapy in patients with relapsed or refractory acute lymphocytic leukemia (ALL) in nonrandomized trials. In some responding patients, induction therapy was followed by multiagent consolidation therapy and bone marrow transplantation (BMT).

    For the treatment of relapsed or refractory non-Hodgkin's lymphoma (NHL)†, in combination with chemotherapy.
    Intravenous dosage
    Adults

    10 to 12 mg/m2 IV in combination with other chemotherapies has been studied in nonrandomized trials. In a multicenter, phase II trial of 54 previously treated NHL patients (prior anthracycline therapy, 89%), idarubicin 12 mg/m2 IV bolus over 15 minutes on day 1 plus etoposide 100 mg/m2/day IV on days 1-3 and ifosfamide 1500 mg/m2/day IV (with mesna 1:1) on days 1-3 repeated every 3 to 4 weeks (mean number of 4.33 cycles; range, 1-6 cycles) led to an overall response rate (ORR) of 72% (complete response (CR), 46%). All patients received oral hydration starting 24 hours prior to chemotherapy, allopurinol 300 mg/m2 PO, and oral bicarbonate solution (to keep urine pH > 7). The median overall survival (OS) time was 17.5 months and the 2-year OS rate was 41%. In another multicenter, phase II study in 38 patients with relapsed or primary resistant high-grade NHL, idarubicin 10 mg/m2 IV on days 1 and 2 (or days 1 and 8) plus etoposide 150 mg/m2/day IV on days 1-3 and ifosfamide 1000 mg/m2/day IV on days 1-5 repeated every 21 days resulted in an ORR of 47.4% (CR, 21.1%) and a median OS time of 6.9 months. All patients in this study received filgrastim until granulocyte recovery. Additionally, idarubicin 12 mg/m2 IV once on day 1 plus etoposide 60 mg/m2 IV every 12 hours for 3 days and cytarabine 1 g/m2 IV over 3 hours every 12 hours for 3 days repeated every 21 days for up to 4 cycles (mean number of 2.6 cycles) led to an ORR of 60% (CR, 20%) and 3-year relapse-free and OS rates of 20% and 15%, respectively, in 30 patients with intermediate- or high-grade NHL who had prior anthracycline exposure in another clinical study. Serious treatment-related toxicity with idarubicin-containing regimens in clinical trials included grade 3 or 4 neutropenia/granulocytopenia, thrombocytopenia, febrile neutropenia; additionally, death attributed to septic shock during severe neutropenia has been reported.

    For the treatment of myeloid blast crisis chronic myelogenous leukemia (CML)†, in combination with cytarabine or imatinib and cytarabine.
    NOTE: Idarubicin has been designated an orphan drug by the FDA for this indication.
    Intravenous dosage
    Adults

    12 mg/m2 IV with cytarabine and with or without imatinib has been studied in small, nonrandomized studies. Idarubicin 12 mg/m2 IV repeated every 14 days plus imatinib 600 mg/day PO and cytarabine 10 mg/day SC until patients returned to chronic phase (CP) followed by maintenance therapy with idarubicin 8 mg/m2 IV repeated every 4 weeks plus imatinib 600 mg orally and cytarabine 10 mg SC once daily until disease progression (median duration of therapy, 11 weeks; range, 4-124 weeks) resulted in a hematologic response rate of 74% (complete hematologic response rate (CHR), 47%) in 19 patients with CML in myeloid blast crisis in a pilot study; additionally, 26% of patients returned to CP. Most patients (n=17) had previously failed treatment with single-agent imatinib. Six patients received an allogeneic stem-cell transplant, including one patient still in myeloid blast phase. The median overall survival time was 23 weeks and the 1-year OS rate was 26%. All patients experienced at least 1 episode of grade 3 or 4 hematologic toxicity and 16 patients (84%) required hospitalization for febrile neutropenia, hemorrhage, pneumonia, cellulitis, and/or central nervous system leukemic infiltration. In a small phase II study in 16 patients with Philadelphia chromosome-positive CML in myeloid blast crisis who received idarubicin 12 mg/m2/day IV for 3 days and cytarabine 600 mg/m2 IV twice daily for 5 days, no patient achieved a CHR but 4 patients (25%) had a second CP. Three patients in second CP received maintenance therapy with interferon alfa-2b 5 million international units/day SQ and cytarabine 20 mg/day SQ for 14 days per month until disease progression. The median OS time was 16 weeks for all patients; however, the median OS time for the 4 patients in second CP was 31.1 weeks (range, 16.1 to 111 weeks). All patients became pancytopenic and transfusion dependent following induction therapy with idarubicin and cytarabine and 3 patients died due to septic complications during bone marrow aplasia.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    12 mg/m2 IV; maximum cumulative lifetime idarubicin dose: 150 mg/m2 IV.

    Geriatric

    12 mg/m2 IV; maximum cumulative lifetime idarubicin dose: 150 mg/m2 IV  .

    Adolescents

    Safety and efficacy have not been established. Doses up to 12 mg/m2 IV have been given off-label for AML; maximum cumulative lifetime idarubicin dose: 150 mg/m2 IV.

    Children

    Safety and efficacy have not been established. Doses up to 12 mg/m2 IV have been given off-label for AML; maximum cumulative lifetime dosage limits should be considered.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Total bilirubin 2.5—5 mg/dL: reduce recommended dose by 50%.
    Total bilirubin > 5 mg/dL: do not administer.

    Renal Impairment

    Dosage adjustment is recommended in patients with a serum creatinine greater than 2.5 mg/dL, but no quantitative recommendations are available.

    ADMINISTRATION

     
    CAUTION: Observe and exercise appropriate precautions for handling, preparing, and administering cytotoxic drugs.

    Injectable Administration

    Idarubicin is a vesicant and should not be administered intramuscularly or subcutaneously. If evidence of extravasation occurs during administration, the infusion should be stopped and completed via another vein, preferably in another limb. The affected area should be elevated and treated with cold compresses. Appropriate long-term follow-up of the area is recommended.
    Idarubicin is intended for administration under the supervision of a physician who is experienced in leukemia chemotherapy.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Idarubicin is administered intravenously as a rapid infusion over 10—15 minutes via Y-site or 3-way stopcock into a free-flowing IV infusion of 0.9% Sodium Chloride injection or 5% Dextrose injection. A Butterfly needle inserted into a large vein may be used. Idarubicin has been given as prolonged (4-hour) infusions as well.
     
    Reconstitution:
    Do not use diluents containing bacteriostatic agents to reconstitute idarubicin powder for injection.
    Reconstitute 5, 10, or 20 mg of idarubicin with 5 mL, 10 mL, or 20 mL, respectively, of nonbacteriostatic water for injection to give an IV solution containing 1 mg of idarubicin per ml. Insert needle into vial carefully because the vial contents are under pressure. The reconstituted solution is hypotonic and is stable for 72 hours at room temperature or 1 week under refrigeration.
    Vial contents are under negative pressure to decrease aerosol formation during reconstitution. Care should be taken when the needle is inserted into the vial.

    STORAGE

    Idamycin PFS:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 36 to 46 degrees F
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Anthracycline hypersensitivity

    Idarubicin is should be avoided in patients with known idarubicin or other anthracycline hypersensitivity or anthracenedione hypersensitivity. Idarubicin therapy is not recommended in patients who have reached their total cumulative doses of doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones.

    Bone marrow suppression, herpes infection, infection, neutropenia, requires a specialized care setting, requires an experienced clinician, thrombocytopenia, varicella, viral infection

    Severe bone marrow suppression is a relative contraindication to idarubicin depending upon the etiology of the suppression. Patients with acute leukemia may require treatment with idarubicin despite severe bone marrow suppression. Idarubicin should be used cautiously in patients with bone marrow suppression, coagulopathy, or in those who have received previous myelosuppressive therapy such as chemotherapy or radiotherapy. Therefore, this drug requires an experienced clinician knowledgeable in the use of cancer chemotherapy. Administration of idarubicin requires a specialized care setting such as a hospital or treatment facility. Patients with preexisting marrow suppression, including neutropenia and/or thrombocytopenia, should be allowed to recover their counts prior to idarubicin administration. Patients should be treated for any active infection prior to receiving idarubicin. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

    Dental disease, dental work

    Myelosuppressive effects of idarubicin can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

    Intramuscular injections

    Intramuscular injections should not be administered to patients with platelet counts < 50,000/mm3 who are receiving idarubicin. IM injections may cause bleeding, bruising, or hematomas due to idarubicin-induced thrombocytopenia.

    Extravasation, intramuscular administration, subcutaneous administration

    Idarubicin is a vesicant. Extravasations of idarubicin infusions should be avoided. Patients should be closely monitored during IV infusions for signs and symptoms of extravasation such as poor blood return, pain and swelling. If extravasation occurs, stop the infusion and remove the tubing. Attempt to aspirate the drug prior to removing the needle. Elevate the affected area and treat with ice packs. As this can be a progressive injury, appropriate long-term follow-up is required. Intramuscular administration and subcutaneous administration of idarubicin should be avoided due to severe skin and tissue necrosis which may occur.

    Hepatic disease, jaundice

    Idarubicin should be used cautiously in patients with hepatic disease and/or jaundice. Since hepatic impairment can affect the disposition of idarubicin, liver function should be evaluated using serum bilirubin as an indicator prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if bilirubin serum levels exceeded 2 mg%. However, in one Phase III trial, patients with bilirubin levels between 2.6 and 5 mg% received the anthracycline with a 50% reduction in dose. Dose reduction of idarubicin should be considered if the bilirubin levels are above the normal range (see Dosage).

    Renal impairment

    Doses of idarubicin should be adjusted for severe renal impairment or renal failure, although specific guidelines are not available and < 5% of the dose is eliminated renally. Kidney function should be evaluated with serum creatinine as an indicator prior to and during treatment. In a number of Phase III clinical trials, treatment was not given if creatinine serum levels exceeded 2 mg%. Dose reduction of idarubicin should be considered if the creatinine levels are above the normal range.

    Pregnancy

    Idarubicin is classified as FDA pregnancy risk category D and should not be administered during pregnancy because of the possibility of teratogenic effects. Idarubicin was teratogenic and embryotoxic in animals at doses less than the recommended human dose on a body surface area basis. There have been no adequate and well-controlled studies of idarubicin in pregnant women. There has been a report of a fetal fatality after maternal exposure in the second trimester. Women of childbearing potential should be cautioned to avoid getting pregnant. If a woman becomes pregnant during therapy, she should be advised of the potential risks to the fetus.

    Breast-feeding

    It is unknown whether idarubicin is excreted in breast milk. Breast-feeding should be discontinued during idarubicin therapy because of the possibility of severe adverse reactions to the infant.

    Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, tumor lysis syndrome (TLS)

    Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and decreased urine output may be indicative of idarubicin-induced tumor lysis syndrome (TLS). Appropriate measures (e.g. aggressive hydration and allopurinol) must be taken to prevent severe electrolyte imbalances and renal toxicity during and following chemotherapy administration in patients with large chemosensitive tumors.

    Acute myocardial infarction, alcoholism, angina, bradycardia, cardiac arrhythmias, cardiac disease, cardiotoxicity, children, coronary artery disease, diabetes mellitus, females, geriatric, heart failure, hypertension, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, maximum cumulative lifetime dose, myocardial infarction, QT prolongation, radiation therapy, thyroid disease, ventricular dysfunction

    Idarubicin is a cardiotoxin and can cause congestive heart failure due to its effects on cardiac myofibrils. Patients with preexisting cardiac disease including heart failure, angina, left ventricular dysfunction (i.e., ejection fraction < 50%), recent or acute myocardial infarction, or cardiac arrhythmias are not good candidates to receive idarubicin. Angina and arrhythmias are relative contraindications to idarubicin therapy, depending on the degree of clinical impairment. Although it is suggested that idarubicin causes less cardiotoxicity than other agents in its class, patients should be observed closely for signs of cardiotoxicity if idarubicin is given. The risk of cardiac toxicity may be higher in children < 2 years or geriatric patients > 60 years of age, patients who have received prior anthracycline therapy, and those who are receiving or have received radiation therapy to the mediastinal-pericardial area. Patients > 60 years of age undergoing induction therapy with idarubicin experienced an increased incidence of cardiac effects vs. younger patients. Females and children may be more sensitive to the cardiotoxic effects of anthracyclines. Children treated with anthracyclines may develop late cardiotoxicity. Due to the risk of long-term cardiotoxicity, it has been recommended that children treated with anthracyclines should undergo screening with ECGs and echocardiograms every 2 years and 24-hour continuous ECGs and radionuclide angiograms every 5 years. Generally, patients with a left ventricular ejection fraction < 50% are not considered candidates for anthracycline therapy; the risks vs. benefits of anthracycline therapy must be carefully considered in these patients. Patients should be observed closely for signs of idarubicin-induced cardiotoxicity; early recognition is essential for successful treatment. Establishment of baseline left ventricular function and periodic monitoring are recommended. Patients currently receiving idarubicin should wait at least 4 weeks following the last dose before undergoing periodic cardiac evaluation to allow cardiac function to return to baseline. Although the most definitive technique for assessing anthracycline-induced cardiotoxicity is endomyocardial biopsy, echocardiograms or serial gated cardiography (MUGA) scans may also indicate if a patient is developing cardiotoxicity. A left ventricular ejection fraction < 50% or an absolute decrease of 10—20% in left ventricular heart function are indications to discontinue anthracycline therapy. Cardiotoxicity is dose related; although there is little data, the maximum cumulative lifetime dose of idarubicin is suggested to be 150 mg/m2 IV, and should only be exceeded with extreme caution. Use idarubicin with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation.

    Accidental exposure, ocular exposure

    Use care to avoid accidental exposure to idarubicin during preparation, handling, and administration. The use of protective gowns, gloves and goggles is recommended. Following skin or ocular exposure, skin and eyes should be thoroughly rinsed.

    Vaccination

    Vaccination during chemotherapy or radiation therapy should be avoided because the antibody response is suboptimal. When chemotherapy is being planned, vaccination should precede the initiation of chemotherapy by >= 2 weeks. The administration of live vaccines to immunocompromised patients should be avoided. Those undergoing chemotherapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.

    ADVERSE REACTIONS

    Severe

    myocardial infarction / Delayed / 0-16.0
    atrial fibrillation / Early / 0-16.0
    vomiting / Early / 0-5.0
    oral ulceration / Delayed / 0-5.0
    nausea / Early / 0-5.0
    seizures / Delayed / 4.0-4.0
    pancytopenia / Delayed / 10.0
    tissue necrosis / Early / Incidence not known
    AV block / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    heart failure / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known

    Moderate

    bleeding / Early / 63.0-63.0
    bullous rash / Early / 0-46.0
    chest pain (unspecified) / Early / 0-16.0
    peripheral neuropathy / Delayed / 7.0-7.0
    elevated hepatic enzymes / Delayed / 0-5.0
    neutropenia / Delayed / 10.0
    thrombocytopenia / Delayed / 10.0
    anemia / Delayed / 10.0
    leukopenia / Delayed / 10.0
    radiation recall reaction / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    ST-T wave changes / Rapid / Incidence not known

    Mild

    infection / Delayed / 95.0-95.0
    alopecia / Delayed / 77.0-77.0
    abdominal pain / Early / 73.0-73.0
    diarrhea / Early / 73.0-73.0
    urticaria / Rapid / 0-46.0
    rash (unspecified) / Early / 0-46.0
    fever / Early / 26.0-26.0
    headache / Early / 20.0-20.0
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abciximab: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Albuterol: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Alfuzosin: (Major) Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should be dont only after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (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. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Amitriptyline: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Amitriptyline; Chlordiazepoxide: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Anagrelide: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Anticoagulants: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Antithrombin III: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Antithymocyte Globulin: (Moderate) Because antithymocyte globulin is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
    Apixaban: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Apomorphine: (Major) 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. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Caution should be exercised when prescribing apomorphine concomitantly with drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Arformoterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Argatroban: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Aripiprazole: (Moderate) Aripiprazole is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Arsenic Trioxide: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include arsenic trioxide.
    Artemether; Lumefantrine: (Major) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as idarubicin, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if idarubicin must be used with or after artemether; lumefantrine treatment. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. Therefore, asenapine should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Aspirin, ASA; Dipyridamole: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Atomoxetine: (Moderate) Caution and close monitoring are recommended during concurrent use of atomoxetine and anthracycline therapy. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Azelastine; Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Azithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and idarubicin should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concurrent use may increase the risk of QT prolongation.
    Bacillus Calmette-Guerin Vaccine, BCG: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Beclomethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with idarubicin. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Acute cardiotoxicity and cumulative, dose-dependent cardiomyopathy may also occur during administration of idarubicin. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Betamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Betrixaban: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Bivalirudin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Budesonide; Formoterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Buprenorphine: (Major) If concurrent use of an anthracycline chemotherapy agent and buprenorphine is necessary, cautious use and close monitoring are advisable. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. 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.
    Buprenorphine; Naloxone: (Major) If concurrent use of an anthracycline chemotherapy agent and buprenorphine is necessary, cautious use and close monitoring are advisable. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. 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.
    Celecoxib: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and idarubicin; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Chloroquine: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include chloroquine.
    Chlorpromazine: (Major) Phenothiazines have been associated a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines such as chlorpromazine. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use or should be avoided. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Ciclesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Cilostazol: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Ciprofloxacin: (Moderate) Ciprofloxacin has been reported to cause QT prolongation and torsade de pointes. Use ciprofloxacin with caution with daunorubicin, doxorubicin, epirubicin, and idarubicin as acute cardiotoxicity can occur during administration; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Cisapride: (Severe) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Because of the potential for torsades de pointes (TdP), use of cisapride with idarubicin is contraindicated.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval, such as daunorubicin, doxorubicin, epirubicin, and idarubicin, is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Class IA Antiarrhythmics: (Major) Class IA antiarrhythmics (disopyramide, procainamide, and quinidine) are associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Clomipramine: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Clopidogrel: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. Additionally, treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Antineoplastic agents with a possible risk of QT prolongation and TdP (torsade de pointes) include anthracyclines. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Codeine; Phenylephrine; Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Codeine; Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Corticosteroids: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Corticotropin, ACTH: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Cortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with idarubicin. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Cyclobenzaprine: (Moderate) Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes (TdP), particularly in the event of acute overdose. Cyclobenzaprine administration is associated with QT prolongation and torsades de pointes (TdP) and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Cyclophosphamide: (Major) Use caution if cyclophosphamide is used concomitantly with anthracyclines, as there may be an increased risk of cardiotoxicity. Concurrent administration of cyclophosphamide and doxorubicin has resulted in an increase in exposure to doxorubicinol, a more cardiotoxic metabolite of doxorubicin. Additionally, concurrent treatment with doxorubicin (including doxorubicin liposomal) has been reported to exacerbate cyclophosphamide-induced hemorrhagic cystitis.
    Cyclosporine: (Major) Concurrent use of idarubicin with other agents which cause bone marrow or immune suppression such as cyclosporine may result in additive effects.
    Dabigatran: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dalteparin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Danaparoid: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Use ritonavir cautiously in patients taking other drugs known to prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dasatinib: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include dasatinib.
    Deflazacort: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Degarelix: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include degarelix.
    Desflurane: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Desipramine: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Desirudin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with idarubicin, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Dexamethasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Dextromethorphan; Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Diclofenac: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diflunisal: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Dipyridamole: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dofetilide: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Because of the potential for TdP, dofetilide is contraindicated with any drugs associated with QT prolongation such as daunorubicin, doxorubicin, epirubicin, or idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dolasetron: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Dolasetron injection is contraindicated for use for the prevention of chemotherapy-induced nausea and vomiting because the risk of QT prolongation is higher with the doses used for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Dolasetron should be used cautiously with anthracyclines such as daunorubicin or doxorubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Acute cardiotoxicity can occur during administration of daunorubicin (including daunorubicin liposomal), doxorubicin (including doxorubicin liposomal), epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Caution and close monitoring are recommended during concurrent use of donepezil and anthracycline therapy.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Acute cardiotoxicity can occur during administration of daunorubicin (including daunorubicin liposomal), doxorubicin (including doxorubicin liposomal), epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Caution and close monitoring are recommended during concurrent use of donepezil and anthracycline therapy.
    Doxepin: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dronedarone: (Severe) Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Droperidol: (Major) As droperidol can prolong the QT interval and cause torsades de pointes (TdP), it should NOT be used with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like anthracyclines. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Edoxaban: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Efavirenz: (Major) Although data are limited, coadministration of efavirenz and idarubicin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and idarubicin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Eliglustat: (Major) Coadministration of eliglustat and idarubicin increases the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Concomitant use of drugs known to prolong the QT interval should be done with caution and close monitoring. Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Enflurane: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Enoxaparin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Eptifibatide: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Monitor patients closely for QT prolongation. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Erythromycin: (Major) Erythromycin is an inhibitor of CYP3A4 and P-glycoprotein (P-gp); doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Erythromycin has a possible risk of causing QT prolongation and torsades de pointes (TdP). Avoid coadministration of erythromycin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Erythromycin; Sulfisoxazole: (Major) Erythromycin is an inhibitor of CYP3A4 and P-glycoprotein (P-gp); doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Erythromycin has a possible risk of causing QT prolongation and torsades de pointes (TdP). Avoid coadministration of erythromycin and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Escitalopram: (Moderate) Escitalopram is associated with a possible risk for QT prolongation and torsade de pointes (TdP), and should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risk for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of these agents; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Esomeprazole; Naproxen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Etodolac: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ezogabine: (Major) Ezogabine has been associated with QT prolongation. The manufacturer of ezogabine recommends caution during concurrent use of medications known to increase the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    Fenoprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fingolimod: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsade de pointes (TdP). 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. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Flecainide: (Moderate) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Fluconazole: (Major) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP) and should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Flucytosine: (Minor) Flucytosine can cause significant hematologic toxicity. It should be used cautiously with all antineoplastic agents, especially those that cause bone marrow depression.
    Fludrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Flunisolide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Fluphenazine: (Minor) Acute cardiotoxicity can occur during the administration of anthracyclines; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with anthracyclines include fluphenazine.
    Flurbiprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fluticasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Fluticasone; Salmeterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Fluticasone; Vilanterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and idarubicin. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Fondaparinux: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Formoterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as idarubicin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as anthracyclines, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together.
    Gemifloxacin: (Major) Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5-10 hours following oral administration of gemifloxacin. 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. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Glycopyrrolate; Formoterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Goserelin: (Moderate) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Granisetron: (Major) According to the manufacturer, caution is advised if granisetron is administered to patients receiving drugs known to cause QT prolongation, including cardio-toxic chemotherapy. Cumulative high-dose anthracyclines may aggravate cardiac arrhythmias, including QT prolongation, that are possible with granisetron. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Halofantrine: (Severe) Acute cardiotoxicity can occur during the administration of daunorubicin; although, the incidence is rare. Agents associated with prolonging the QT interval, which can cause torsades de pointes, such as halofantrine, should be not be used with daunorubicin due to the risk of additive acute cardiac effects.
    Halogenated Anesthetics: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Haloperidol: (Major) Haloperidol is an inhibitor of CYP2D6 and doxorubicin is a major CYP2D6 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Haloperidol has a possible risk of causing QT prolongation and torsades de pointes (TdP). Avoid coadministration of haloperidol and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity
    Halothane: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Heparin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Hydrocortisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and idarubicin. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Hydroxyzine: (Moderate) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include certain anthracyclines. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ibuprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (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. Ibutilide should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes has not been reported. Since iloperidone can prolong the QT interval, it should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Imipramine: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Indacaterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indomethacin: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with idarubicin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Intranasal Influenza Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Isoflurane: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with itraconazole include the anthracyclines. Acute cardiotoxicity can occur during administration of daunorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ketoprofen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ketorolac: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lapatinib: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with idarubicin include lapatinib.
    Lepirudin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Leuprolide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Leuprolide; Norethindrone: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Leuprolide should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Levalbuterol: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levofloxacin: (Major) Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Levomethadyl: (Severe) Acute cardiotoxicity can occur during the administration of idarubicin. Other agents associated with prolonging the QT interval, such as levomethadyl, which can cause torsades de pointes, should be used cautiously with idarubicin due to the risk of additive acute cardiac effects following the administration of idarubicin.
    Lithium: (Moderate) Lithium should be used cautiously with idarubicin. Lithium has been associated with QT prolongation. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Live Vaccines: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Long-acting beta-agonists: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Moderate) Coadministration of loperamide with anthracycline therapy may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest. Acute cardiac toxicities have also occurred during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias
    Loperamide; Simethicone: (Moderate) Coadministration of loperamide with anthracycline therapy may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest. Acute cardiac toxicities have also occurred during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias
    Lopinavir; Ritonavir: (Major) Lopinavir; ritonavir administration is associated with QT prolongation. Coadministration of lopinavir; ritonavir with other drugs that prolong the QT interval, such as daunorubicin, doxorubicin, epirubicin, and idarubicin, may result in additive QT prolongation and should be done with caution and close monitoring. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. In addition, doxorubicin is a CYP3A4 substrate and lopinavir; ritonavir inhibits CYP3A4. Coadministration may result in elevated plasma concentrations of doxorubicin and an added risk of adverse reactions such as QT prolongation. (Major) The use of ritonavir could result in QT prolongation. Use ritonavir cautiously in patients taking other drugs known to prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Maprotiline: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously and with close monitoring with idarubicin include maprotiline.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Measles/Mumps/Rubella Vaccines, MMR: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefenamic Acid: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefloquine: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Acute cardiotoxicity can occur during the administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. In addition, mefloquine inhibits P-glycoprotein (P-gp) and daunorubicin is a P-gp substrate. Concurrent use may increase the serum concentrations of daunorubicin, further increasing the risk for QT prolongation.
    Meloxicam: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meperidine; Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Mesoridazine: (Severe) Acute cardiotoxicity can occur during the administration of daunorubicin; although, the incidence is rare. Agents associated with prolonging the QT interval, which can cause torsades de pointes, such as mesoridazine, should be not be used with daunorubicin due to the risk of additive acute cardiac effects.
    Metaproterenol: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Methadone: (Major) Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Since methadone can prolong the QT interval, it should be used cautiously with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Metronidazole: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Mifepristone, RU-486: (Major) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Mifepristone should be used cautiously with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and idarubicin. Coadminister with caution. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Mometasone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Moxifloxacin: (Major) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Nabumetone: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Sumatriptan: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Nilotinib: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with idarubicin include nilotinib.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Norfloxacin: (Moderate) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Nortriptyline: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Octreotide: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. 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. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ofloxacin: (Major) Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP). Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Olanzapine: (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Olodaterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Use ritonavir cautiously in patients taking other drugs known to prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ondansetron: (Major) If ondansetron and idarubicin must be coadministered, ECG monitoring is recommended. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of idarubicin with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of idarubicin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Oxaprozin: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    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) Paliperidone has been associated with QT prolongation; however, torsade de pointes has not been reported. Since paliperidone can prolong the QT interval, it should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Pasireotide: (Major) Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as idarubicin, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and idarubicin must be continued, closely monitor the patient for QT interval prolongation. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentamidine: (Major) Pentamidine has been associated with QT prolongation. Pentamidine should be administered cautiously with daunorubicin or doxorubicin. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Pentosan: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Perphenazine: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with idarubicin include perphenazine, Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with idarubicin.
    Perphenazine; Amitriptyline: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with idarubicin include perphenazine, Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with idarubicin. (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Phenylephrine; Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as idarubicin. Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, pimozide is contraindicated with any drugs associated with QT prolongation such as the anthracyclines (e.g. daunorubicin, doxorubicin, epirubicin, or idarubicin). Acute cardiotoxicity can occur during administration of anthracyclines; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Additionally, pimozide is a mild inhibitor of CYP2D6 and doxorubicin is a CYP2D6 substrate; clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin.
    Pirbuterol: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Piroxicam: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Platelet Inhibitors: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Posaconazole: (Major) Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes and should be used with caution and close clinical monitoring with idarubicin. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Prasugrel: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Primaquine: (Moderate) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Prochlorperazine: (Minor) Phenothiazines have been reported to prolong the QT interval. Therefore, prochlorperazine should be used cautiously with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Promethazine: (Moderate) Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Use with caution with other agents that may cause QT prolongation. Promethazine carries a possible risk of QT prolongation. In addition, promethazine is a CYP2D6 inhibitor and doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. If avoidance of promethazine with doxorubicin is not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Propafenone: (Major) Propafenone is a CYP2D6 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP2D6 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Propafenone has a possible risk of causing QT prolongation and torsades de pointes (TdP). Avoid coadministration of propafenone and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Protriptyline: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Quetiapine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Quinine: (Major) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP) and its use with other drugs that may prolong the QT interval should be avoided. Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. 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. Ranolazine should be used cautiously with drugs that prolong the QT interval, such as daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. In addition, doxorubicin is a CYP3A4 substrate and ritonavir inhibits CYP3A4. Coadministration may result in elevated plasma concentrations of doxorubicin and an added risk of adverse reactions such as QT prolongation.
    Regadenoson: (Moderate) Regadenoson has been associated with QT prolongation and should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Ribociclib: (Major) Avoid coadministration of ribociclib with idarubicin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with idarubicin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Concomitant use may increase the risk for QT prolongation.
    Rilpivirine: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsades de pointes; however, data are currently lacking to establish causality in association with torsades de pointes. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone has potential to prolong the QT interval, it should be used cautiously with daunorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Use ritonavir cautiously in patients taking other drugs known to prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Rivaroxaban: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Rofecoxib: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Rotavirus Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Rubella Virus Vaccine Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Salmeterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Saquinavir: (Major) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Sertraline: (Moderate) There have been post-marketing reports of QT prolongation and Torsade de Pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Sevoflurane: (Major) Since halogenated anesthetics can prolong the QT interval, they should be used cautiously and with close clinical monitoring with anthracyclines due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Short-acting beta-agonists: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and antineoplastic agents should be avoided. Concurrent administration of antineoplastic agents with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving antineoplastic agents may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of antineoplastic agents prior to initiating therapy with sipuleucel-T.
    Smallpox Vaccine, Vaccinia Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Solifenacin: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Solifenacin should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Sorafenib: (Major) Sorafenib has been associated with QT prolongation. If sorafenib and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy. In clinical studies, sorafenib has been administered with a variety of antineoplastic agents at their commonly used dosing regimens, including doxorubicin. Coadministration of sorafenib with doxorubicin resulted in a 21% increase in the doxorubicin AUC. The clinical significance is unknown. Daunorubicin concentrations may also increase with coadministration of sorafenib as daunorubicin is a P-glycoprotein (PGP) substrate and sorafenib is a PGP inhibitor in vitro.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Sotalol should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Sparfloxacin: (Severe) Acute cardiotoxicity can occur during the administration of anthracyclines, although, the incidence is rare. Other agents associated with prolonging the QT interval, which can cause torsades de pointes, such as sparfloxacin, should be used cautiously with anthracyclines, due to the risk of additive acute cardiac effects following the administration of anthracyclines.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Sulindac: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sunitinib: (Major) Sunitinib can prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Tacrolimus: (Major) Tacrolimus causes QT prolongation and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. In addition, reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended when coadministrating tacrolimus with other substrates of CYP3A4 that also have the potential to prolong the QT interval such as doxorubicin. In addition, concurrent use of idarubicin with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
    Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and idarubicin due to an increased risk of QT prolongation. 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. Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage.
    Telavancin: (Major) Telavancin has been associated with QT prolongation and should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Telithromycin: (Major) Telithromycin is associated with QT prolongation and torsades de pointes (TdP) and should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. In addition, doxorubicin is a substrate for CYP3A4 and telithromycin is a strong inhibitor of CYP3A4. Coadministration may result in an increased concentration of doxorubicin and an increased risk of QT prolongation.
    Terbutaline: (Minor) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). Therefore, it should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Thioridazine: (Severe) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Acute cardiotoxicity can occur during anthracycline (e.g., daunorubicin, doxorubicin, idarubicin, epirubicin) treatment; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Additionally, thioridazine is an inhibitor of CYP2D6 and doxorubicin is a CYP2D6 substrate; clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin.
    Ticagrelor: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Ticlopidine: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Tinzaparin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Tiotropium; Olodaterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tirofiban: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Tizanidine: (Moderate) Tizanidine administration may result in QT prolongation. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Tolmetin: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tolterodine: (Moderate) Tolterodine has been associated dose-dependent prolongation of the QT interval. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation. Tolterodine should be used cautiously with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Toremifene: (Major) Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner and should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Trastuzumab: (Major) Avoid the concomitant use of anthracyclines and trastuzumab due to the risk of increased cardiac dysfunction. Anthracycline use after trastuzumab therapy may result in an additive or potentially synergistic increase in the risk of cardiomyopathy. Avoid anthracycline-based therapy for up to 7 months after trastuzumab is discontinued. If anthracycline therapy is necessary during this time period, monitor cardiac function.
    Trazodone: (Major) The manufacturer of trazodone recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Tricyclic antidepressants: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Trifluoperazine: (Minor) Phenothiazines have been reported to prolong the QT interval. Therefore, trifluoperazine should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Trimipramine: (Minor) Tricyclic antidepressants (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). TCAs should be used with caution and close monitoring with other drugs that may prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Triptorelin: (Moderate) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Triptorelin should be used with caution with cardiotoxic drugs. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    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.
    Typhoid Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Umeclidinium; Vilanterol: (Moderate) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with idarubicin include the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Valdecoxib: (Major) Due to the thrombocytopenic effects of idarubicin, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs known to prolong the QT interval, such as idarubicin. Vandetanib can prolong the QT interval in a concentration-dependent manner; torsade de pointes (TdP) and sudden death have been reported. Rarely, acute cardiotoxicity can occur during administration of anthracyclines; acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. If coadministration is necessary, monitor the ECG. If the QTcF is more than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, restart vandetanib at a lower dose.
    Vardenafil: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction) The effect of vardenafil on the QT interval should be considered when prescribing the drug. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Varicella-Zoster Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Vemurafenib: (Major) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with idarubicin include vemurafenib.
    Venlafaxine: (Moderate) Venlafaxine administration is associated with a possible risk of QT prolongation; torsades de pointes (TdP) has been reported with post-marketing use and should be used cautiously with other drugs with a possible risk for QT prolongation and TdP including daunorubicin, doxorubicin, epirubicin, and idarubicin. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Vorapaxar: (Moderate) Avoid coadministration if possible. An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as anthracyclines. In addition, ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor; doxorubicin is a major substrate of both CYP3A4 and P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with idarubicin. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Acute cardiotoxicity can occur during administration of idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Vorinostat: (Moderate) Since vorinostat can prolong the QT interval, it should be used cautiously with daunorubicin, doxorubicin, epirubicin, and idarubicin due to the potential risks for anthracycline cardiac toxicity. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    Warfarin: (Moderate) Due to the thrombocytopenic effects of anthracyclines, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants. In addition, rivaroxaban is a mild P-glycoprotein (P-gp) inhibitor and doxorubicin is a major substrate of P-gp. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of rivaroxaban and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Yellow Fever Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Ziprasidone: (Severe) Acute cardiotoxicity can occur during the administration of idarubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Because of the potential for torsades de pointes (TdP), use of ziprasidone with idarubicin is contraindicated.

    PREGNANCY AND LACTATION

    Pregnancy

    Idarubicin is classified as FDA pregnancy risk category D and should not be administered during pregnancy because of the possibility of teratogenic effects. Idarubicin was teratogenic and embryotoxic in animals at doses less than the recommended human dose on a body surface area basis. There have been no adequate and well-controlled studies of idarubicin in pregnant women. There has been a report of a fetal fatality after maternal exposure in the second trimester. Women of childbearing potential should be cautioned to avoid getting pregnant. If a woman becomes pregnant during therapy, she should be advised of the potential risks to the fetus.

    It is unknown whether idarubicin is excreted in breast milk. Breast-feeding should be discontinued during idarubicin therapy because of the possibility of severe adverse reactions to the infant.

    MECHANISM OF ACTION

    The mechanism of action of idarubicin is similar to that of other anthracycline antineoplastics. Idarubicin complexes with DNA by intercalating between DNA base pairs, causing the helix to change shape. Idarubicin has a higher affinity for DNA intercalation than daunorubicin and is more readily taken up into cells. This simple act of changing the conformation of DNA can interfere with strand elongation by inhibiting DNA polymerase and inhibit protein synthesis due to effects on RNA polymerase. Idarubicin inhibits the uptake of thymidine into cancer cells and normal fibroblasts at lower concentrations than other anthracyclines. As with other anthracylines, idarubicin inbibits topoisomerase II, an enzyme responsible for repairing faulty sections of DNA, causing double-strand DNA breaks. This occurs most commonly in the G2-phase of the cell cycle, although, in general, idarubicin is considered non-cell cycle specific. Idarubicin does not form free radicals to the same extent as doxorubicin or daunorubicin. This may account for the decrease in clinical cardiotoxicity seen with idarubicin. The alcohol metabolite of idarubicin is as active as the parent compound and plays an important role in the activity of the drug. Idarubicin and its metabolite seem to be less susceptible to multiple drug resistance (MDR, P-gp) than daunorubicin and its metabolites. Studies have shown that cyclosporine and other modulators of MDR may increase the cytotoxicity of the alcohol metabolite of idarubicin. Idarubicin may offer an advantage over other anthracyclines in the treatment of leukemia and other diseases which may overexpress MDR. Resistance to idarubicin may also be mediated by changes in topoisomerase II activity.

    PHARMACOKINETICS

    Idarubicin is currently administered by slow IV injection (over 10—15 minutes).  Idarubicin is converted to an active metabolite, idarubicinol, via ketoreductase transformation. This metabolite is equally active as the parent compound and 16—122 times more potent in antileukemic activity than other anthracycline metabolites. Following administration of idarubicin to adult or pediatric patients, systemic exposure to idarubicinol is greater than that of idarubicin. Idarubicin and idarubicinol concentrate in nucleated blood cells. Both idarubicin and idarubicinol are 97% bound to plasma proteins. Idarubicin metabolism occurs primarily in the liver, however, plasma clearance values almost twice that of hepatic blood flow suggest extensive extrahepatic metabolism. The plasma half-life of idarubicin as a single agent averages 22 hours. The elimination half-life of idarubicinol is >45 hours. This rapidly leads to plasma concentrations of the metabolite 2—4 times the parent compound. Elimination is primarily biliary and to a lesser extent renal (<5%). Biliary elimination involves conjugates with sulfate or glucuronide. Dosage reduction in patients with elevated bilirubin concentrations is recommended (see Dosage). Total elimination from the body may happen very slowly because of distribution to blood cells with slow release from this site. The small amount of renal elimination may cause red or orange discoloration of the urine.

    Oral Route

    An oral dosage form has been investigated and demonstrates a bioavailability of 24—39%. Peak concentrations are not achieved for 3 hours after oral administration.