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  • CLASSES

    Small Molecule Antineoplastic Breakpoint Cluster Region-Abelson (BCR-ABL) Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Oral multi-tyrosine kinase inhibitor
    Used in adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy; also used in pediatric patients with chronic-phase Ph+ CML
    Severe myelosuppression has been reported

    COMMON BRAND NAMES

    Sprycel

    HOW SUPPLIED

    Sprycel Oral Tab: 20mg, 50mg, 70mg, 80mg, 100mg, 140mg

    DOSAGE & INDICATIONS

    For the treatment of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).
    NOTE: The FDA has designated dasatinib as an orphan drug for the treatment of CML.
    For the treatment of myeloid or lymphoid blast-phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
    Oral dosage
    Adults

    140 mg orally once daily until disease progression or unacceptable toxicity occurs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The dasatinib dosage may be increased to 180 mg/day if an inadequate hematologic or cytogenetic response is achieved with the initial dose. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. Treatment with dasatinib 140 mg once daily was compared with dasatinib 70 mg twice daily in patients with imatinib-resistant or imatinib-intolerant myeloid blast-phase (MBP; n = 149) or lymphoid blast-phase (LBP; n = 61) chronic myelogenous leukemia (CML) in a multicenter, randomized, phase III, non-inferiority trial. Treatment with once-daily dasatinib resulted in similar efficacy and improved tolerability compared with twice-daily dosing in this trial; therefore, dasatinib 140 mg once daily is the recommended dosage. After 2 years of follow-up, treatment with once-daily dasatinib resulted in a major hematologic response (MHR) rate (primary endpoint) of 28% in patients with MBP-CML (n = 75) and 42% in patients with LBP-CML (n = 33); the median time to MHR was 2 months in both MBP-CML and LBP-CML patients and the median MHR duration times were 8 months and 5 months, respectively. In Philadelphia chromosome-positive patients who received once-daily dasatinib, the major cytogenetic response rate was 25% (complete cytogenetic response (cCyR) rate, 14%) in 72 MBP-CML patients and 50% (cCyR rate, 38%) in 32 LBP-CML patients. The median progression-free survival times with once-daily dasatinib were 3.8 months in MBP-CML patients and 4.7 months in LBP-CML patients; the median overall survival times were 7.9 months and 11.4 months, respectively.

    For the treatment of chronic-phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
    Oral dosage
    Adults

    100 mg orally once daily until disease progression or unacceptable toxicity occurs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The dasatinib dosage may be increased to 140 mg/day if an inadequate hematologic or cytogenetic response is achieved with the initial dose. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. Four dasatinib dosages (100 mg once daily, 50 mg twice daily, 140 mg once daily, and 70 mg twice daily) were evaluated in adult patients with imatinib-resistant or imatinib-intolerant Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia (Ph+ CP-CML) in a multinational, randomized, phase III, non-inferiority trial (n = 670; the CA180-034 trial). In patients with imatinib-resistant Ph+ CP-CML, treatment with once-daily dasatinib resulted in a noninferior major cytogenetic response (mCyR) rate (primary endpoint) compared with twice-daily dasatinib (52% vs. 49%); additionally, dasatinib 100 mg/day was noninferior to dasatinib 140 mg/day for mCyR (50% vs. 51%). Treatment with dasatinib 100 mg once daily (n = 167) resulted in similar efficacy and improved tolerability compared with other dosing arms in this trial; therefore, dasatinib 100 mg PO once daily is the recommended dosage. At a 2-year follow-up, the mCyR rate was 63% and the complete cytogenetic response (cCyR) rate was 50% in Ph+ CP-CML patients in the dasatinib 100 mg once daily treatment arm. After approximately 72 months, 31% of patients were still receiving therapy in the dasatinib 100 mg/day arm; the median duration of therapy was 29.3 months (range, 0.1 to 78 months) for all treatment arms. In patients in the dasatinib 100 mg/day treatment arm, the major molecular response rate was 43%, and the estimated 6-year progression-free survival (PFS) and overall survival (OS) rates were 49% and 71%, respectively. Factors predictive of improved 6-year PFS and OS rates included a partial cytogenetic response or cCyR at 3 or 6 months or a reduction in BCR-ABL to 10% or less at 3 or 6 months.

    For the treatment of newly diagnosed chronic-phase Ph+ CML.
    NOTE: Dasatinib was not active against the T315I mutation based on in vitro data.
    Oral dosage
    Adults

    100 mg orally once daily until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The dasatinib dosage may be increased to 140 mg/day if an inadequate hematologic or cytogenetic response is achieved with the initial dose. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. The confirmed complete cytogenetic response (cCyR) rate at 12 months (primary endpoint) was significantly higher in adult patients with newly diagnosed Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia who received dasatinib compared with imatinib (77% vs. 66%; p = 0.007) in a multinational, randomized, phase III trial (n = 519; the DASISION trial). The major molecular response (MMR) rate was also significantly higher with dasatinib (52% vs. 34%, p less than 0.0001). At a minimum follow-up of 60 months, the cCyR rate was 83% in the dasatinib arm and 79% in the imatinib arm; the median times to cCyR were 3.1 months and 5.8 months, respectively. The MMR rate was also higher with dasatinib therapy (76.4% vs. 64.2%). The estimated 5-year overall survival rates were 90.9% and 89.6% in patients who received dasatinib and imatinib, respectively.

    For the treatment of accelerated-phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
    Oral dosage
    Adults

    140 mg orally once daily until disease progression or unacceptable toxicity occurs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The dasatinib dosage may be increased to 180 mg/day if an inadequate hematologic or cytogenetic response is achieved with the initial dose. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. Treatment with dasatinib 140 mg once daily (n = 158) was compared with dasatinib 70 mg twice daily (n = 159) in patients with imatinib-resistant or imatinib-intolerant accelerated-phase chronic myelogenous leukemia (AP-CML) in a multicenter, randomized, phase III, non-inferiority trial. Treatment with once-daily dasatinib resulted in similar efficacy and improved tolerability compared with twice-daily dosing in this trial; therefore, dasatinib 140 mg PO once daily is the recommended dosage. At a median follow-up time of 15 months, treatment with once-daily dasatinib resulted in a major hematologic response (MHR) rate (primary endpoint) of 66% in patients with AP-CML; the median time to MHR was 1.9 months. In patients who received once-daily dasatinib, the major cytogenetic response rate was 39% (complete cytogenetic response rate, 32%), the median progression-free survival was 25.1 months, and the estimated 12- and 24-month overall survival rates were 78% and 63%, respectively.

    For the treatment of chronic-phase Ph+ CML.
    Oral dosage
    Adolescents and Children

    Take the dasatinib dose (based on body weight) orally once daily as follows: 10 kg to less than 20 kg = 40 mg; 20 kg to less than 30 kg = 60 mg; 30 kg to less than 45 kg = 70 mg; 45 kg or greater = 100 mg. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Recalculate the dose at least every 3 months based on changes in body weight. Although patients 1 year of age and older may receive dasatinib therapy; tablet dosing is not recommended for patients weighing less than 10 kg. If an inadequate hematologic or cytogenetic response is achieved with the initial dose, the dasatinib dose may be increased as follows: 40 mg/day, increase to 50 mg/day; 60 mg/day, increase to 70 mg/day; 70 mg/day, increase to 90 mg/day; 100 mg/day, increase to 120 mg/day. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. In pooled results from 2 open-label, nonrandomized trials, the 24-month complete cytogenetic response (cCyR), major cytogenetic response (mCyR), and major molecular response (MMR) rates were 96.1%, 98%, and 74.5%, respectively, in patients with newly diagnosed, chronic-phase CML (n = 51; median age, 12.8 years; range, 1.9 to 17.8 years) and 82.6%, 89.1%, and 52.2%, respectively, in patients with chronic-phase CML resistant or intolerant to previous treatment with imatinib (n = 46; median age, 13.5 years; range, 2 to 20 years). The median duration times of cCyR, mCyR, MMR were not reached at a median follow-up of 4.5 years in newly diagnosed patients and 5.2 years in imatinib-resistant or -intolerant patients.[60087]

    For the treatment of Philadelphia chromosome-positive (Ph+) acute lymphocytic leukemia (ALL).
    NOTE: Dasatinib has been designated as an orphan drug by the FDA for the treatment of Ph+ ALL.
    For the treatment of Ph+ ALL with resistance or intolerance to prior therapy.
    Oral dosage
    Adults

    140 mg orally once daily until disease progression or unacceptable toxicity occurs. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The dasatinib dosage may be increased to 180 mg/day if an inadequate hematologic or cytogenetic response is achieved with the initial dose. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity.[60087] Treatment with dasatinib 140 mg once daily (n = 40) was compared with dasatinib 70 mg twice daily (n = 44) in patients aged 15 to 80 years with imatinib-resistant or imatinib-intolerant, Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in a multicenter, randomized, phase 3, non-inferiority trial. Treatment with once-daily dasatinib resulted in similar efficacy and improved tolerability compared with twice-daily dosing in this trial; therefore, dasatinib 140 mg once daily is the recommended dosage. After 2 years of follow-up, treatment with once-daily dasatinib resulted in a major hematologic response (MHR) rate (primary endpoint) of 38% in patients with Ph+ ALL; the median time to MHR was 1.2 months and the median MHR duration was 4.6 months. In patients who received once-daily dasatinib, the major cytogenetic response rate was 70% (complete cytogenetic response rate, 50%), the median progression-free survival time was 4 months, and the median overall survival time was 6.5 months.[55097]

    For the treatment of newly diagnosed Ph+ ALL, in combination with chemotherapy.
    Oral dosage
    Adolescents and Children

    Begin dasatinib therapy (based on body weight) orally once daily starting on or before day 15 of induction chemotherapy as follows: 10 kg to less than 20 kg = 40 mg; 20 kg to less than 30 kg = 60 mg; 30 kg to less than 45 kg = 70 mg; 45 kg or greater = 100 mg. Continue therapy for 2 years. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Recalculate the dose at least every 3 months based on changes in body weight. Although patients 1 year of age and older may receive dasatinib therapy; tablet dosing is not recommended for patients weighing less than 10 kg. Temporary interruption of therapy and a dose reduction may be necessary in patients who develop toxicity. The 3-year event-free survival rate was 64.1% in a cohort of pediatric patients (median age, 10.4 years; range, 2.6 to 17.9 years) with newly diagnosed B-cell precursor Ph+ ALL who received dasatinib in combination with chemotherapy (the AIEOP-BFM ALL 2000 protocol) in a multicenter study (n = 78; study CA180372). Bone marrow with less than 5% lymphoblast was achieved in 96% of patients after induction therapy and 97% of patients after consolidation therapy.[60087]

    MAXIMUM DOSAGE

    Adults

    140 mg/day PO for chronic-phase CML; 180 mg/day PO for advanced-phase CML and Ph+ ALL.

    Geriatric

    140 mg/day PO for chronic-phase CML; 180 mg/day PO for advanced-phase CML and Ph+ ALL.

    Adolescents

    30 kg to less than 45 kg: 70 mg/day PO for Ph+ ALL; 90 mg/day PO for chronic-phase CML.45 kg or more: 100 mg/day PO for Ph+ ALL; 120 mg/day PO for chronic-phase CML.

    Children

    10 kg to less than 20 kg: 40 mg/day PO for Ph+ ALL; 50 mg/day PO for chronic-phase CML.20 kg to less than 30 kg: 60 mg/day PO for Ph+ ALL; 70 mg/day PO for chronic-phase CML.30 kg to less than 45 kg: 70 mg/day PO for Ph+ ALL; 90 mg/day PO for chronic-phase CML.45 kg or more: 100 mg/day PO for Ph+ ALL; 120 mg/day PO for chronic-phase CML.

    Infants

    Safety and efficacy not established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in patients with baseline hepatic impairment are not available; it appears that no initial dosage adjustments are needed.
    Treatment-related Toxicity in Pediatric Ph+ ALL patients:
    One-level dose reduction:
    For starting dose of 40 mg, reduce to 20 mgFor starting dose of 60 mg, reduce to 40 mgFor starting dose of 70 mg, reduce to 60 mgFor starting dose of 100 mg, reduce to 80 mg
    Two-level dose reduction:
    For dose of 20 mg, lower tablet dose not availableFor dose of 40 mg, reduce to 20 mgFor dose of 60 mg, reduce to 50 mgFor dose of 80 mg, reduce to 70 mg
    Direct bilirubin level greater than 5-times the upper limit of normal (ULN) or AST/ALT level greater than 15-times the ULN: Hold dasatinib until the toxicity has recovered to grade 1 or less; resume therapy at the original starting dose. Resume dasatinib at a reduced dose if the toxicity recurs.[60087]

    Renal Impairment

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

    ADMINISTRATION

     
    Observe and exercise usual precautions for handling and administering cytotoxic drugs. If tablets become crushed or broken, health care personnel should wear disposable chemotherapy gloves when handling and administering dasatinib tablets. Personnel who are pregnant should avoid exposure to crushed or broken tablets.

    Oral Administration

    Oral Solid Formulations

    Take in the morning or evening with or without a meal.
    Swallow whole; do not crush, cut, or chew tablets.
    Do not drink grapefruit juice during treatment.
    Separate antacid medication administration by at least 2 hours; avoid the concomitant use of H2-receptor antagonists or proton pump inhibitors.
    If you miss a dose, skip that dose and take the next scheduled dose at your regular time.

    STORAGE

    Sprycel:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, neutropenia, thrombocytopenia

    Severe hematologic toxicity (e.g., thrombocytopenia, neutropenia, anemia) has been reported with dasatinib therapy. Toxicity is usually reversible and occurs earlier and more frequently in patients with advanced-phase chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) than in patients with chronic-phase (CP)-CML. Evaluate complete blood counts (CBCs) every 2 weeks for 12 weeks and then every 3 months thereafter or as clinically indicated in patients with CP-CML. Evaluate CBCs weekly for the first 2 months and then monthly thereafter or as clinically indicated in adult patients with advanced-phase CML or Ph+ ALL. In pediatric patients with Ph+ ALL, obtain CBCs prior to the start of each block of chemotherapy and as clinically indicated; during consolidation therapy, evaluate CBCs every 2 days until blood cell count recovery. Therapy interruption, dose reduction, or discontinuation may be necessary in patients who develop severe hematologic toxicity. Hematopoietic growth factors have been used in patients with resistant myelosuppression.[60087]

    Anticoagulant therapy, bleeding, GI bleeding, intracranial bleeding

    Serious bleeding (e.g., GI bleeding, intracranial bleeding) has been reported with dasatinib therapy; some cases resulted in death. Treatment interruptions and transfusions may be necessary if severe bleeding occurs. In clinical studies, most bleeding events were associated with severe thrombocytopenia. In vitro, dasatinib-related platelet dysfunction was observed. Concomitant antiplatelet or anticoagulant therapy may increase the risk of bleeding in dasatinib-treated patients.

    Edema, pericardial effusion, pleural effusion

    Severe fluid retention/edema (e.g., pleural effusions, pericardial effusion, pulmonary edema) has been reported with dasatinib therapy. Evaluate patients with symptoms of fluid retention (e.g., new or worsened dyspnea on exertion or at rest, pleuritic chest pain, dry cough) with a chest X-ray or other diagnostic imaging. Management may include diuretic and/or short term steroid therapy; patients with pleural effusions may require thoracentesis and/or oxygen. Therapy interruption or a dose reduction may be necessary in patients who develop severe fluid retention.

    Alcoholism, cardiac arrhythmias, cardiac disease, diabetes mellitus, females, heart failure, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, QT prolongation, thyroid disease

    QT prolongation has been reported rarely with dasatinib therapy. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia prior to starting dasatinib therapy. Use dasatinib with caution in patients with congenital long QT syndrome and who are taking antiarrhythmic or other drugs that may cause QT prolongation. Females, elderly patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, hepatic dysfunction, or patients who have received high-cumulative dose anthracycline therapy may also be at increased risk for QT prolongation. Cardiac adverse events (e.g., cardiac arrhythmias, congestive heart failure) have been reported with dasatinib therapy. Monitor patients for signs or symptoms of cardiac disease/dysfunction during dasatinib therapy.

    Lactase deficiency

    Inform patients that dasatinib tablets contain 189 mg of lactose monohydrate in a 140-mg dose and 135 mg of lactose monohydrate in a 100-mg dose; Use dasatinib with caution in patients with lactose intolerance/lactase deficiency.

    Tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS) has been reported in patients who were resistant to prior imatinib therapy. Maintain adequate hydration and monitor serum electrolyte and uric acid levels prior to and during therapy; initiate a uric acid lowering agent prior to starting dasatinib if necessary. Patients with advanced disease and/or those with a high tumor burden may be at greater risk for developing TLS; monitor these patients frequently.

    Pulmonary hypertension

    Pulmonary hypertension/pulmonary arterial hypertension (PAH) has been reported with dasatinib therapy. PAH may occur up to 1 year or longer after starting dasatinib. Evaluate patients for signs (e.g., fluid retention, hypoxia) and symptoms (e.g., cough, dyspnea, fatigue) of cardiopulmonary disease at baseline and during treatment. Permanently discontinue therapy in patients who develop PAH; this adverse event may be reversible after dasatinib is stopped.

    Geriatric

    Geriatric patients (aged 65 years or older) may be more likely to experience the following dasatinib adverse reactions: abdominal distention, appetite disturbance, congestive heart failure, cough, diarrhea, dizziness, dyspnea, fatigue, lower GI bleeding, hypertension, pericardial effusion, pleural effusion, pulmonary edema, and weight loss. Monitor elderly patients closely for toxicity during dasatinib therapy.

    Children, growth inhibition, infants, neonates

    Growth inhibition has been reported in pediatric patients with chronic-phase chronic myelogenous leukemia (CML) who received dasatinib; therefore, monitor bone growth and development in pediatric patients. The safety and efficacy of dasatinib have been established in children 1 year of age or older with chronic-phase CML and Philadelphia chromosome-positive acute lymphocytic leukemia; it has not been studied in neonates and infants.[60087]

    Pregnancy

    Dasatinib may cause fetal harm or neonatal death when administered to a pregnant woman. Females of reproductive potential should avoid pregnancy; apprise women of the potential hazard to the fetus. Dasatinib crosses the placenta and has been measured in fetal plasma and amniotic fluid at concentrations comparable to maternal plasma. Adverse fetal and infant outcomes reported from women treated with dasatinib during pregnancy include congenital malformations (e.g., neural tube defects), hydrops fetalis, fetal leukopenia and thrombocytopenia, and harmful pharmacological effects.

    Contraception requirements, infertility, reproductive risk

    Counsel patients about the reproductive risk of dasatinib and discuss contraception requirements. Females of reproductive potential should avoid pregnancy and use effective contraception during and for 30 days after treatment with dasatinib. Women who become pregnant while receiving dasatinib should be apprised of the potential hazard to the fetus. Dasatinib may cause infertility by damaging female and male reproductive tissues. Results from repeat-dose toxicity studies in multiple animal species indicate the potential for dasatinib to impair reproductive function and fertility.

    Breast-feeding

    Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended during dasatinib therapy and for 2 weeks after the final dose. It is unknown whether dasatinib is excreted in human breast-milk.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 29.0-96.0
    thrombocytopenia / Delayed / 22.0-88.0
    anemia / Delayed / 13.0-82.0
    oral ulceration / Delayed / 0-60.0
    elevated hepatic enzymes / Delayed / 0-47.0
    hypokalemia / Delayed / 0-40.0
    diarrhea / Early / 0-31.0
    hypotension / Rapid / 0-26.0
    musculoskeletal pain / Early / 0-25.0
    headache / Early / 0-25.0
    anorexia / Delayed / 0-22.0
    exfoliative dermatitis / Delayed / 0-21.0
    erythema multiforme / Delayed / 0-21.0
    pulmonary edema / Early / 0-21.0
    visual impairment / Early / 0.1-20.0
    hyponatremia / Delayed / 0-19.0
    hypocalcemia / Delayed / 0-19.0
    hypophosphatemia / Delayed / 7.0-18.0
    abdominal pain / Early / 0-17.0
    fever / Early / 0-17.0
    nausea / Early / 0-11.0
    hyperbilirubinemia / Delayed / 0-11.0
    sinusitis / Delayed / 0-10.0
    enterocolitis / Delayed / 1.0-10.0
    hypertension / Early / 0-10.0
    dyspnea / Early / 0-10.0
    bleeding / Early / 1.0-9.0
    GI bleeding / Delayed / 2.0-9.0
    dehydration / Delayed / 0-9.0
    fluid retention / Delayed / 5.0-8.0
    rash / Early / 0-7.0
    infection / Delayed / 0-7.0
    peripheral neuropathy / Delayed / 0-7.0
    ocular hemorrhage / Delayed / 0-6.0
    epistaxis / Delayed / 0-6.0
    erythema / Early / 0-6.0
    edema / Delayed / 0-6.0
    pulmonary hypertension / Delayed / 0.1-5.0
    fatigue / Early / 0-4.0
    heart failure / Delayed / 0-4.0
    cardiomyopathy / Delayed / 2.0-4.0
    pleural effusion / Delayed / 0-4.0
    pericardial effusion / Delayed / 0-4.0
    intracranial bleeding / Delayed / 0-3.0
    maculopapular rash / Early / 0-2.0
    vesicular rash / Delayed / 0-2.0
    skin irritation / Early / 0-2.0
    peptic ulcer / Delayed / 0.1-1.0
    constipation / Delayed / 0-1.0
    vomiting / Early / 0-1.0
    pancreatitis / Delayed / 0-1.0
    pruritus / Rapid / 0-1.0
    cholecystitis / Delayed / 0.1-1.0
    rhabdomyolysis / Delayed / 0.1-1.0
    osteonecrosis / Delayed / 0.1-1.0
    ventricular tachycardia / Early / 0.1-1.0
    pericarditis / Delayed / 0.1-1.0
    cough / Delayed / 0-1.0
    bronchospasm / Rapid / 0.1-1.0
    hearing loss / Delayed / 0.1-1.0
    proteinuria / Delayed / 0.1-1.0
    renal failure (unspecified) / Delayed / 0.1-1.0
    tumor lysis syndrome (TLS) / Delayed / 0.1-1.0
    erythema nodosum / Delayed / 0.1-1.0
    thrombosis / Delayed / 0-1.0
    growth inhibition / Delayed / 0-1.0
    red cell aplasia / Delayed / 0-0.1
    rectal fistula / Delayed / 0-0.1
    ileus / Delayed / 0-0.1
    vasculitis / Delayed / 0-0.1
    cardiac arrest / Early / 0-0.1
    myocarditis / Delayed / 0-0.1
    acute respiratory distress syndrome (ARDS) / Early / 0-0.1
    seizures / Delayed / 0-0.1
    optic neuritis / Delayed / 0-0.1
    stroke / Early / 0-0.1
    spontaneous fetal abortion / Delayed / 0-0.1
    pulmonary embolism / Delayed / 0-0.1
    Stevens-Johnson syndrome / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    atrial flutter / Early / Incidence not known
    nephrotic syndrome / Delayed / Incidence not known
    thrombotic microangiopathy / Delayed / Incidence not known

    Moderate

    stomatitis / Delayed / 1.0-10.0
    gastritis / Delayed / 1.0-10.0
    colitis / Delayed / 1.0-10.0
    atopic dermatitis / Delayed / 1.0-10.0
    hyperuricemia / Delayed / 1.0-10.0
    chest pain (unspecified) / Early / 1.0-10.0
    palpitations / Early / 1.0-10.0
    sinus tachycardia / Rapid / 1.0-10.0
    pneumonitis / Delayed / 1.0-10.0
    blurred vision / Early / 1.0-10.0
    depression / Delayed / 1.0-10.0
    vaginal bleeding / Delayed / 0-6.0
    hematuria / Delayed / 0-6.0
    hematoma / Early / 0-6.0
    osteopenia / Delayed / 0-5.2
    lymphopenia / Delayed / 0.1-1.0
    lymphadenopathy / Delayed / 0.1-1.0
    QT prolongation / Rapid / 0-1.0
    esophagitis / Delayed / 0.1-1.0
    dysphagia / Delayed / 0.1-1.0
    skin ulcer / Delayed / 0.1-1.0
    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 0.1-1.0
    bullous rash / Early / 0.1-1.0
    hepatitis / Delayed / 0.1-1.0
    cholestasis / Delayed / 0.1-1.0
    hypoalbuminemia / Delayed / 0.1-1.0
    angina / Early / 0.1-1.0
    dysphonia / Delayed / 0.1-1.0
    ascites / Delayed / 0.1-1.0
    amnesia / Delayed / 0.1-1.0
    conjunctivitis / Delayed / 0.1-1.0
    confusion / Early / 0.1-1.0
    phlebitis / Rapid / 0.1-1.0
    livedo reticularis / Delayed / 0-0.1
    ataxia / Delayed / 0-0.1
    photophobia / Early / 0-0.1
    peripheral edema / Delayed / 10.0
    interstitial lung disease / Delayed / Incidence not known
    hypoxia / Early / Incidence not known

    Mild

    chills / Rapid / 1.0-21.0
    myalgia / Early / 0-13.0
    flushing / Rapid / 1.0-10.0
    dyspepsia / Early / 1.0-10.0
    xerosis / Delayed / 1.0-10.0
    acne vulgaris / Delayed / 1.0-10.0
    urticaria / Rapid / 1.0-10.0
    hyperhidrosis / Delayed / 1.0-10.0
    alopecia / Delayed / 1.0-10.0
    asthenia / Delayed / 1.0-10.0
    weakness / Early / 1.0-10.0
    dysgeusia / Early / 1.0-10.0
    drowsiness / Early / 1.0-10.0
    dizziness / Early / 1.0-10.0
    xerophthalmia / Early / 1.0-10.0
    insomnia / Early / 1.0-10.0
    tinnitus / Delayed / 1.0-10.0
    weight loss / Delayed / 1.0-10.0
    weight gain / Delayed / 1.0-10.0
    petechiae / Delayed / 0-6.0
    ecchymosis / Delayed / 0-6.0
    muscle cramps / Delayed / 5.0-5.0
    gastroesophageal reflux / Delayed / 0.1-1.0
    photosensitivity / Delayed / 0.1-1.0
    panniculitis / Delayed / 0.1-1.0
    malaise / Early / 0.1-1.0
    arthralgia / Delayed / 0-1.0
    syncope / Early / 0.1-1.0
    tremor / Early / 0.1-1.0
    lacrimation / Early / 0.1-1.0
    anxiety / Delayed / 0.1-1.0
    libido decrease / Delayed / 0.1-1.0
    menstrual irregularity / Delayed / 0.1-1.0
    gynecomastia / Delayed / 0.1-1.0
    vertigo / Early / 0.1-1.0
    increased urinary frequency / Early / 0.1-1.0

    DRUG INTERACTIONS

    Abarelix: (Major) Abarelix may prolong the QT interval and lead to additive effects when given concurrently with dasatinib.
    Abciximab: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. Abciximab is contraindicated for use in patients with a platelet count of less than 100,000 cells/microliters. Patients with thrombocytopenia are at increased risk of bleeding complications. Thus, antineoplastic agents that cause clinically significant thrombocytopenia could increase the bleeding risk associated with abciximab.
    Aclidinium; Formoterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Alfuzosin: (Moderate) Use dasatinib with caution in combination with alfuzosin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Alfuzosin may prolong the QT interval in a dose-dependent manner.
    Aluminum Hydroxide: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Amiodarone: (Major) Avoid coadministration of amiodarone and dasatinib due to the potential for QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid coadministration of dasatinib and clarithromycin due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to clarithromycin with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of clarithromycin in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue clarithromycin or stop dasatinib until clarithromycin is discontinued. Allow a washout of approximately 1 week after clarithromycin is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of dasatinib and clarithromycin due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to clarithromycin with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of clarithromycin in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue clarithromycin or stop dasatinib until clarithromycin is discontinued. Allow a washout of approximately 1 week after clarithromycin is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include dasatinib. In addition, due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Antacids: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Anticoagulants: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Antithrombin III: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Apalutamide: (Major) Avoid coadministration of dasatinib and apalutamide due to the potential for decreased dasatinib exposure and reduced efficacy. If concomitant use is unavoidable, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Apixaban: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with dasatinib as concurrent use may increase the risk of QT prolongation. 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 vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Arformoterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Argatroban: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Aripiprazole: (Moderate) Monitor for evidence of QT prolongation if aripiprazole and dasatinib are coadministered. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include arsenic trioxide.
    Artemether; Lumefantrine: (Major) Avoid the concomitant administration of dasatinib and artemether; lumefantrine due to the potential for QT prolongation. Consider ECG monitoring if coadministration cannot be avoided, In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval. (Major) Avoid the concomitant administration of dasatinib and artemether; lumefantrine due to the potential for QT prolongation. Consider ECG monitoring if coadministration cannot be avoided. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Artemether; lumefantrine is associated with prolongation of the QT interval.
    Asenapine: (Major) Avoid coadministration of dasatinib and asenapine due to the potential for QT prolongation. Asenapine has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Separate the administration of dasatinib and sodium bicarbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Aspirin, ASA; Dipyridamole: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Atazanavir: (Major) Avoid coadministration of dasatinib and atazanavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to atazanavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of atazanavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If atazanavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of dasatinib and atazanavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to atazanavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of atazanavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If atazanavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively. (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Atomoxetine: (Moderate) Use dasatinib with caution in combination with atomoxetine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Avoid coadministration of dasatinib and phenobarbital due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to phenobarbital with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Azithromycin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised during coadministration of dasatinib and azithromycin. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Additionally, cases of QT prolongation and TdP have been reported during the post-marketing use of azithromycin.
    Bedaquiline: (Major) Monitor ECGs if bedaquiline is coadministered with dasatinib. Bedaquiline has been reported to prolong the QT interval. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Coadministration may result in additive or synergistic prolongation of the QT interval.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of dasatinib and phenobarbital due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to phenobarbital with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Betrixaban: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and metronidazole. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and metronidazole. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Bivalirudin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Brigatinib: (Moderate) Monitor for a decrease in the efficacy of dasatinib if coadministration with brigatinib is necessary. Dasatinib is a sensitive CYP3A4 substrate. At clinically relevant concentrations, brigatinib induced CYP3A via activation of the pregnane X receptor (PXR); this may decrease concentrations of sensitive CYP3A substrates.
    Budesonide; Formoterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Buprenorphine: (Major) Monitor for evidence of QT prolongation if coadministration of buprenorphine and dasatinib is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Monitor for evidence of QT prolongation if coadministration of buprenorphine and dasatinib is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Calcium Carbonate: (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively. (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Calcium Carbonate; Risedronate: (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Calcium Carbonate; Simethicone: (Moderate) Separate the administration of dasatinib and calcium carbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Carbamazepine: (Major) Avoid coadministration of dasatinib and carbamazepine due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to carbamazepine with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; carbamazepine is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Celecoxib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ceritinib: (Major) Avoid coadministration of dasatinib and ceritinib due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation. An alternative to ceritinib with no or minimal enzyme inhibition potential is recommended if possible. If concomitant use cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of ceritinib in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue ceritinib or stop dasatinib until ceritinib is discontinued. Allow a washout of approximately 1 week after ceritinib is stopped before increasing the dasatinib dose or reinitiating dasatinib. Periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ceritinib is a strong CYP3A4 inhibitor that is associated with concentration-dependent QT prolongation. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Chloramphenicol: (Major) Avoid coadministration of dasatinib and chloramphenicol due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to chloramphenicol with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of chloramphenicol in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue chloramphenicol or stop dasatinib until chloramphenicol is discontinued. Allow a washout of approximately 1 week after chloramphenicol is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Chloroquine: (Major) Avoid coadministration of chloroquine with dasatinib if possible, due to the risk of QT prolongation and torsade de pointes (TdP). Chloroquine administration is associated with an increased risk of QT prolongation and TdP. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Coadministration may further increase the risk of QT prolongation and torsade de pointes.
    Chlorpromazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and chlorpromazine should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Caution is advised when coadministered with other drugs that prolong the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
    Cilostazol: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and cilostazol is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
    Ciprofloxacin: (Moderate) Ciprofloxacin should be used with caution in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes have been reported with ciprofloxacin during postmarketing surveillance. Additionally, in vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Cisapride: (Severe) In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Because of the potential for torsade de pointes (TdP), use of cisapride with dasatinib is contraindicated.
    Citalopram: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of dasatinib and citalopram should be avoided if possible. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Avoid coadministration of dasatinib and clarithromycin due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to clarithromycin with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of clarithromycin in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue clarithromycin or stop dasatinib until clarithromycin is discontinued. Allow a washout of approximately 1 week after clarithromycin is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; clarithromycin is a strong CYP3A4 inhibitor that is associated with an established risk for QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with dasatinib. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Clopidogrel: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and clopidogrel is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
    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, in vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Clozapine therapy may lead to S-T segment depression and flattening or inversion of T waves. In theory, concurrent use of dasatinib and clozapine could produce clinically significant prolongation of the QTc interval.
    Cobicistat: (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Codeine; Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Conivaptan: (Major) Avoid coadministration of dasatinib and conivaptan due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to conivaptan with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of conivaptan in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue conivaptan or stop dasatinib until conivaptan is discontinued. Allow a washout of approximately 1 week after conivaptan is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate; conivaptan is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Crizotinib: (Major) Avoid coadministration of crizotinib with dasatinib due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. 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. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Dabigatran: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Dalteparin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Danaparoid: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Darunavir: (Major) Avoid coadministration of dasatinib and darunavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to darunavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of darunavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If darunavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Darunavir; Cobicistat: (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively. (Major) Avoid coadministration of dasatinib and darunavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to darunavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of darunavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If darunavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively. (Major) Avoid coadministration of dasatinib and darunavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to darunavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of darunavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If darunavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of dasatinib and ritonavir due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to ritonavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of ritonavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If ritonavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Delavirdine: (Major) Avoid coadministration of dasatinib and delavirdine due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to delavirdine with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of delavirdine is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If delavirdine is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Desirudin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with dasatinib, assess the QTc interval before and after increasing the dosage of either medication as concurrent use may increase the risk of QT prolongation. Caution is advised when dasatinib is coadministered with other drugs that prolong the QT interval. Clinically relevant QTc prolongation may occur with deutetrabenazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Dextromethorphan; Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Dextromethorphan; Quinidine: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and quinidine is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinidine administration is associated with QT prolongation and TdP.
    Diclofenac: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Diflunisal: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    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 and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Dipyridamole: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Disopyramide: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and disopyramide is necessary. Disopyramide administration is associated with QT prolongation and TdP. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Dofetilide: (Major) Coadministration of dofetilide and dasatinib is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with dasatinib as concurrent use may increase the risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with dasatinib as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Donepezil: (Moderate) Use donepezil with caution in combination with dasatinib. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with dasatinib. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Dronedarone: (Severe) Concomitant use of dronedarone and dasatinib is contraindicated. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as dasatinib. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal.
    Duvelisib: (Moderate) Monitor for increased toxicity of dasatinib if coadministered with duvelisib. Coadministration may increase the exposure of dasatinib. Dasatinib is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
    Edoxaban: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with dasatinib as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with dasatinib as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with dasatinib as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with dasatinib may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Dasatinib is a substrate and mild inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eliglustat: (Moderate) Use dasatinib with caution in combination with eliglustat as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of dasatinib and cobicistat due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to cobicistat with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of cobicistat is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If cobicistat is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with dasatinib as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering rilpivirine with dasatinib as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Encorafenib: (Major) Avoid coadministration of encorafenib and dasatinib due to QT prolongation. Concurrent use may also result in increased toxicity or decreased efficacy of dasatinib. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. Dasatinib is a sensitive CYP3A4 substrate. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Enoxaparin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Entrectinib: (Major) Avoid coadministration of entrectinib with dasatinib due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Enzalutamide: (Major) Avoid coadministration of dasatinib and enzalutamide due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to enzalutamide with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Eptifibatide: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Eribulin: (Major) ECG monitoring is recommended if eribulin and dasatinib must be coadministered; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Erythromycin: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and erythromycin is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Erythromycin is associated with QT prolongation and TdP.
    Erythromycin; Sulfisoxazole: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and erythromycin is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Erythromycin is associated with QT prolongation and TdP.
    Escitalopram: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and escitalopram is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Escitalopram has been associated with a risk of QT prolongation and TdP.
    Esomeprazole; Naproxen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Etodolac: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ezogabine: (Moderate) Use dasatinib with caution in combination with ezogabine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Ezogabine has also been associated with QT prolongation.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Fenoprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Fingolimod: (Moderate) Use dasatinib with caution in combination with fingolimod as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Dasatinib should be used cautiously and with close monitoring with flecainide. 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. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation.
    Fluconazole: (Severe) Coadministration of fluconazole and dasatinib is contraindicated due to the potential for QT prolongation. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as dasatinib. Coadministration of fluconazole with dasatinib may result in elevated plasma concentrations of dasatinib, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and fluoxetine is necessary. QT prolongation and TdP have been reported in patients treated with fluoxetine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Fluoxetine; Olanzapine: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and olanzapine should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and fluoxetine is necessary. QT prolongation and TdP have been reported in patients treated with fluoxetine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Fluphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and fluphenazine should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Flurbiprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Fluticasone; Salmeterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvoxamine: (Moderate) Use dasatinib with caution in combination with fluvoxamine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Fondaparinux: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with dasatinib. Dasatinib is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with dasatinib, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Formoterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fosamprenavir: (Major) Avoid coadministration of dasatinib and fosamprenavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to fosamprenavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of fosamprenavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If fosamprenavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as dasatinib. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Major) Avoid coadministration of dasatinib and fosphenytoin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to fosphenytoin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; fosphenytoin is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Gemifloxacin: (Moderate) Use dasatinib with caution in combination with gemifloxacin as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 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.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and dasatinib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and dasatinib is necessary. Gilteritinib has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Coadministration has the potential for additive QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with dasatinib due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Glycopyrrolate; Formoterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Granisetron: (Moderate) Use granisetron with caution in combination with dasatinib due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Grapefruit juice: (Major) Instruct patients to avoid grapefruit or grapefruit juice with dasatinib due to the potential for increased dasatinib exposure and subsequent toxicity. Dasatinib is sensitive CYP3A4 substrate and grapefruit is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    H2-blockers: (Major) Do not administer H2-blockers with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an H2-blocker reduced the mean Cmax and AUC of dasatinib by 63% and 61%, respectively.
    Halofantrine: (Severe) Halofantrine may prolong QT interval and lead to additive effects when given concurrently with dasatinib.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dasatinib. Halogenated anesthetics can prolong the QT interval. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation.
    Haloperidol: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if dasatinib and haloperidol are coadministered. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Heparin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and dasatinib. 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. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Hydroxyzine: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if hydroxyzine and dasatinib are coadministered. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Ibuprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ibuprofen; Pseudoephedrine: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ibutilide: (Major) Use caution during concurrent use of dasatinib and ibutilide. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation. 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.
    Idelalisib: (Major) Avoid coadministration of dasatinib and idelalisib due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to idelalisib with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of idelalisib is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If idelalisib is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Iloperidone: (Major) Avoid coadministration of dasatinib and iloperidone due to the potential for QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Iloperidone has also been associated with QT prolongation.
    Indacaterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indinavir: (Major) Avoid coadministration of dasatinib and indinavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to indinavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of indinavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If indinavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Indomethacin: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with dasatinib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of dasatinib and rifampin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifampin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of rifampin decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Isoniazid, INH; Rifampin: (Major) Avoid coadministration of dasatinib and rifampin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifampin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of rifampin decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Itraconazole: (Major) Avoid dasatinib use during and for 2 weeks after discontinuation of itraconazole treatment due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to itraconazole with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of itraconazole in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue itraconazole or stop dasatinib until itraconazole is discontinued. Allow a washout of approximately 2 weeks after itraconazole is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; itraconazole is a strong CYP3A4 inhibitor that is associated with QT prolongation. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with dasatinib due to an increased risk of QT prolongation; dasatinib exposure may also decrease. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Monitor for loss of efficacy of dasatinib. Ivosidenib is a CYP3A4 inducer that has been associated with prolongation of the QTc interval and ventricular arrhythmias. Dasatinib is a sensitive CYP3A4 substrate; in vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Ketoconazole: (Major) Avoid coadministration of dasatinib and ketoconazole due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to ketoconazole with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of ketoconazole in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue ketoconazole or stop dasatinib until ketoconazole is discontinued. Allow a washout of approximately 1 week after ketoconazole is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ketoconazole is a strong CYP3A4 inhibitor that is associated with QT prolongation. Coadministration of ketoconazole increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Ketoprofen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Ketorolac: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with dasatinib. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Lefamulin: (Major) Coadministration of lefamulin tablets is contraindicated with dasatinib due to increased dasatinib exposure which may result in QT prolongation and torsade de pointes (TdP). Avoid use of lefamulin injection with dasatinib. If coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment. Dasatinib is a sensitive CYP3A4 substrate that has the potential to prolong the QT interval. Lefamulin is a CYP3A4 inhibitor that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with dasatinib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Lepirudin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Letermovir: (Moderate) Administering letermovir with dasatinib may increase dasatinib concentration and risk for adverse events. Avoid this combination in patients also receiving cyclosporine, because the magnitude of the interaction may be increased. If use of dasatinib with both letermovir and cyclosporine cannot be avoided, consider a dose decrease of dasatinib. If on 140 mg per day dasatinib, decrease to 40 mg per day. If on 100 mg per day or 70 mg per day of dasatinib, decrease to 20 mg per day. In patients on dasatinib doses of 60 mg or 40 mg daily, do not coadminister with both letermovir and cyclosporine. Dasatinib is a sensitive substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor. The combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Levalbuterol: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levofloxacin: (Moderate) Use dasatinib with caution in combination with levofloxacin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Levofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Lithium: (Moderate) Dasatinib should be used cautiously and with close monitoring with lithium as concurrent use may increase the risk of QT prolongation. Lithium has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with dasatinib due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Long-acting beta-agonists: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and loperamide. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
    Loperamide; Simethicone: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and loperamide. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of dasatinib and lopinavir; ritonavir due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to lopinavir; ritonavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of lopinavir; ritonavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. Allow a washout of approximately 1 week after lopinavir; ritonavir is stopped before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; lopinavir; ritonavir is a strong CYP3A4 inhibitor that is associated with QT prolongation. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively. (Major) Avoid coadministration of dasatinib and ritonavir due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to ritonavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of ritonavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If ritonavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of dasatinib and lumacaftor; ivacaftor due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to lumacaftor; ivacaftor with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as dasatinib. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Magnesium Hydroxide: (Moderate) Separate the administration of dasatinib and antacids by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Maprotiline: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and maprotiline should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Mefenamic Acid: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Mefloquine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering dasatinib with mefloquine. There is evidence that the use of halofantrine after mefloquine causes 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. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Meloxicam: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Meperidine; Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Metaproterenol: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Methadone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and methadone should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. 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). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
    Metronidazole: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and metronidazole. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Midostaurin: (Major) The concomitant use of midostaurin and dasatinib may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms to monitor the QT interval. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia prior to starting dasatinib therapy. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin and in patients who received dasatinib.
    Mifepristone: (Major) Avoid coadministration of dasatinib and mifepristone due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to mifepristone with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of mifepristone is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If mifepristone is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-dependent prolongation of the QT interval. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Mirtazapine: (Moderate) Use caution when using mirtazapine in combination with dasatinib as concurrent use may increase the risk of QT prolongation. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Mitotane: (Major) Avoid coadministration of dasatinib and mitotane due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to mitotane with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; mitotane is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Moxifloxacin: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and moxifloxacin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Nabumetone: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Naproxen: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Naproxen; Pseudoephedrine: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Naproxen; Sumatriptan: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Nefazodone: (Major) Avoid coadministration of dasatinib and nefazodone due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to nefazodone with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of nefazodone is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If nefazodone is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Nelfinavir: (Major) Avoid coadministration of dasatinib and nelfinavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to nelfinavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of nelfinavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If nelfinavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Nevirapine: (Moderate) Dasatinib is metabolized by CYP3A4. Concurrent administration of CYP3A4 inducers like nevirapine may decrease concentrations of dasatinib. If dasatinib must be administered with an inducer of CYP3A4, an increased dose of dasatinib should be considered.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Norfloxacin: (Moderate) Use dasatinib with caution in combination with norfloxacin as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. 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 postmarketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Octreotide: (Moderate) Use dasatinib with caution in combination with octreotide as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Use dasatinib with caution in combination with ofloxacin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dasatinib and olanzapine should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Olodaterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of dasatinib and ritonavir due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to ritonavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of ritonavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If ritonavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Omeprazole; Sodium Bicarbonate: (Moderate) Separate the administration of dasatinib and sodium bicarbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Ondansetron: (Major) ECG monitoring is recommended if ondansetron and dasatinib must be coadministered. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Osimertinib: (Major) Avoid coadministration of dasatinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and dasatinib concomitantly; 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. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Oxaprozin: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Paliperidone: (Major) Avoid coadministration of paliperidone and dasatinib if possible due to the potential for QT prolongation. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Panobinostat: (Major) Coadministration of panobinostat and dasatinib is not recommended due to the potential for QT prolongation. QT prolongation has been reported with panobinostat. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Pasireotide: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and pasireotide. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses.
    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 serious cardiac arrhythmias including QT prolongation, and is considered to have an established risk of torsade de pointes. The drug should be used cautiously in patients receiving agents which may cause QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Pentosan: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Perphenazine: (Minor) Monitor for evidence of QT prolongation during concurrent use of dasatinib and perphenazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Perphenazine; Amitriptyline: (Minor) Monitor for evidence of QT prolongation during concurrent use of dasatinib and perphenazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Phenobarbital: (Major) Avoid coadministration of dasatinib and phenobarbital due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to phenobarbital with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; phenobarbital is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Phenylephrine; Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Phenytoin: (Major) Avoid coadministration of dasatinib and phenytoin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to phenytoin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; phenytoin is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    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 dasatinib. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Coadministration of dasatinib and pimozide is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Pimozide is associated with a well-established risk of QT prolongation and TdP.
    Pirbuterol: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Piroxicam: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Pitolisant: (Major) Avoid coadministration of pitolisant with dasatinib as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Posaconazole: (Severe) Concurrent use of posaconazole and dasatinib is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Increased dasatinib exposure may also occur. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and TdP. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval.
    Prasugrel: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and prasugrel is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
    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. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Primaquine: (Moderate) Due to increased risk of QT prolongation, use dasatinib with caution in combination with primaquine. Both drugs have the potential to prolong the QT interval.
    Primidone: (Major) Avoid coadministration of dasatinib and primidone due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to primidone with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; primidone is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Procainamide: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking procainamide.
    Prochlorperazine: (Minor) Use dasatinib with caution in combination with prochlorperazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Prochlorperazine is also associated with a possible risk for QT prolongation.
    Promethazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and promethazine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Propafenone: (Major) Monitor for evidence of QT prolongation during concurrent use of dasatinib and propafenone. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
    Proton pump inhibitors: (Major) Do not administer proton pump inhibitors with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an proton pump inhibitor reduced the mean Cmax and AUC of dasatinib by 42% and 43%, respectively.
    Quetiapine: (Major) Avoid coadministration of dasatinib and quetiapine due to the potential for QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Quinidine: (Major) Monitor for evidence of QT prolongation and torsade de pointes (TdP) if coadministration of dasatinib and quinidine is necessary. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Quinidine administration is associated with QT prolongation and TdP.
    Quinine: (Major) Concurrent use of quinine and dasatinib should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. In vitro studies have shown that dasatinib also has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
    Ranolazine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and ranolazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval.
    Ribociclib: (Major) Avoid coadministration of ribociclib with dasatinib due to the risk of QT prolongation and increased exposure to dasatinib. Ribociclib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Dasatinib is a sensitive substrate of CYP3A4 that also has the potential to prolong the QT interval.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with dasatinib due to the risk of QT prolongation and increased exposure to dasatinib. Ribociclib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Dasatinib is a sensitive substrate of CYP3A4 that also has the potential to prolong the QT interval.
    Rifampin: (Major) Avoid coadministration of dasatinib and rifampin due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to rifampin with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. Concurrent use of rifampin decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with dasatinib as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Risperidone: (Moderate) Use dasatinib with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Ritonavir: (Major) Avoid coadministration of dasatinib and ritonavir due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to ritonavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of ritonavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If ritonavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ritonavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Rivaroxaban: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Rofecoxib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Romidepsin: (Moderate) Monitoring of electrolytes and ECGs at baseline and periodically during treatment is recommended if dasatinib and romidepsin are coadministered. Romidepsin has been reported to prolong the QT interval. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Salmeterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Saquinavir: (Severe) Concurrent use of dasatinib and saquinavir boosted with ritonavir is contraindicated due to the potential for life threatening arrhythmias such as torsade de pointes (TdP). Increased dasatinib exposure may also occur. Saquinavir boosted with ritonavir is a strong CYP3A4 inhibitor that causes dose-dependent QT and PR prolongation. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval.
    Sertraline: (Moderate) Use caution and monitor patients for QT prolongation when administering dasatinib with sertraline. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Short-acting beta-agonists: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving dasatinib due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Sodium Bicarbonate: (Moderate) Separate the administration of dasatinib and sodium bicarbonate by at least 2 hours if these agents are used together. The simultaneous administration of an antacid with dasatinib decreased the Cmax and AUC of dasatinib by 58% and 55%, respectively.
    Solifenacin: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and solifenacin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Solifenacin has been associated with dose-dependent prolongation of the QT interval. TdP has been reported with postmarketing use, although causality was not determined.
    Sorafenib: (Moderate) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with dasatinib is necessary; correct any electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib has been associated with QT prolongation. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Sotalol: (Minor) Use caution during concurrent use of sotalol and dasatinib. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation. 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.
    St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of dasatinib and St. John's wort due to the potential for decreased dasatinib exposure and reduced efficacy. Consider an alternative to St. John's wort with less potential for enzyme induction. If coadministration cannot be avoided, consider an increased dose of dasatinib and monitor for toxicity. Dasatinib is a CYP3A4 substrate; St. John's wort is a strong CYP3A4 inducer. Concurrent use of another strong CYP3A4 inducer decreased the mean Cmax and AUC of dasatinib by 81% and 82%, respectively.
    Sulindac: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with dasatinib. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Sunitinib can also prolong the QT interval.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with dasatinib. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen with dasatinib 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. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Telavancin: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and telavancin. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Telavancin has been associated with QT prolongation.
    Telithromycin: (Major) Avoid coadministration of dasatinib and telithromycin due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to telithromycin with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of telithromycin in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue telithromycin or stop dasatinib until telithromycin is discontinued. Allow a washout of approximately 1 week after telithromycin is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Terbutaline: (Minor) Use dasatinib with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tetrabenazine: (Major) Avoid coadministration of tetrabenazine and dasatinib due to the potential for QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Tetrabenazine causes a small increase in the corrected QT interval (QTc).
    Thioridazine: (Severe) Coadministration of dasatinib and thioridazine is contraindicated due to the potential for QT prolongation and torsade de pointes (TdP). In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Thioridazine is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
    Ticagrelor: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and ticagrelor is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
    Ticlopidine: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and ticlopidine is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant platelet inhibitors may increase the risk of hemorrhage.
    Tinzaparin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Tiotropium; Olodaterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Tipranavir: (Major) Avoid coadministration of dasatinib and tipranavir due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to tipranavir with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of tipranavir is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If tipranavir is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Tolmetin: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Tolterodine: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and tolterodine as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
    Toremifene: (Major) Avoid coadministration of dasatinib with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Trazodone: (Major) Avoid coadministration of trazodone and dasatinib due to the potential for QT prolongation and torsade de pointes (TdP). Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Tricyclic antidepressants: (Minor) Monitor for evidence of QT prolongation during concurrent use of dasatinib and a tricyclic antidepressant. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. 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).
    Trifluoperazine: (Minor) Monitor for evidence of QT prolongation during concurrent use of dasatinib and trifluoperazine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving dasatinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Umeclidinium; Vilanterol: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Valdecoxib: (Major) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, 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. Caution should be exercised if patients are required to take medications that inhibit platelet function or anticoagulants concomitantly with dasatinib.
    Vandetanib: (Major) Avoid coadministration of vandetanib with dasatinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
    Vardenafil: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and vardenafil. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    Venlafaxine: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) during concurrent use of dasatinib and venlafaxine. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Venlafaxine administration is associated with a possible risk of QT prolongation; TdP has reported with postmarketing use.
    Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and dasatinib. Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with dasatinib, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
    Voriconazole: (Major) Avoid coadministration of dasatinib and voriconazole due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to voriconazole with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of voriconazole in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue voriconazole or stop dasatinib until voriconazole is discontinued. Allow a washout of approximately 1 week after voriconazole is stopped before increasing the dasatinib dose or reinitiating dasatinib. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; voriconazole is a strong CYP3A4 inhibitor that is associated QT prolongation and rare cases of TdP. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
    Vorinostat: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and vorinostat. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
    Warfarin: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
    Ziprasidone: (Major) Concomitant use of ziprasidone and dasatinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.

    PREGNANCY AND LACTATION

    Pregnancy

    Dasatinib may cause fetal harm or neonatal death when administered to a pregnant woman. Females of reproductive potential should avoid pregnancy; apprise women of the potential hazard to the fetus. Dasatinib crosses the placenta and has been measured in fetal plasma and amniotic fluid at concentrations comparable to maternal plasma. Adverse fetal and infant outcomes reported from women treated with dasatinib during pregnancy include congenital malformations (e.g., neural tube defects), hydrops fetalis, fetal leukopenia and thrombocytopenia, and harmful pharmacological effects.

    Due to the potential for serious adverse reactions in the nursing infant, breast-feeding is not recommended during dasatinib therapy and for 2 weeks after the final dose. It is unknown whether dasatinib is excreted in human breast-milk.

    MECHANISM OF ACTION

    Dasatinib is an oral multi-tyrosine kinase inhibitor that was specifically designed to inhibit SRC tyrosine kinase, which acts as a signal transducer in several molecular pathways within the cell, but was also found to inhibit BCR-ABL and imatinib-resistant mutations of BCR-ABL. The BCR-ABL tyrosine kinase is the resultant protein of the chromosome translocation (Philadelphia chromosome, Ph) which is associated with chronic myeloid leukemia (CML) and certain types of acute lymphocytic leukemia (Ph+ ALL). Changes in the BCR-ABL protein, such as point mutations and changes in the conformation of the proteins that change the imatinib-binding site, and gene amplification lead to imatinib-resistance; however, dasatinib's chemical structural allows for activity in the majority of imatinib-resistant stages of CML and Ph+ ALL. Dasatinib more effectively inhibits the BCR-ABL kinase than imatinib. Additional rationale for the clinical response seen with dasatinib include the facts that dasatinib is not a substrate for multidrug resistance protein (P-glycoprotein), which can lead to increased concentrations within hematopoietic cells that highly express this protein and dasatinib also targets many other kinases that may contribute to the cytogenetic response. Interestingly there may not be cross-resistance between dasatinib and imatinib, as studies have identified several BCR-ABL mutations that confer resistance to dasatinib but not imatinib. In vitro studies of head and neck squamous cells and non-small cell lung cancer cells indicate that dasatinib inhibited migration and invasion in all cell lines and induced cell cycle arrest (blocking G1-S transition) and apoptosis in some cell lines. These effects are consistent with dasatinib's inhibition of SRC tyrosine kinase.

    PHARMACOKINETICS

    Dasatinib is administered orally. The apparent volume of distribution is 2,505 L (coefficient of variance (CV), 93%), the mean terminal half-life is 3 to 5 hours, and the mean apparent oral clearance is 363.8 L/hr (CV, 81.3%). Dasatinib and its active metabolite are highly bound to human plasma proteins (96% and 93%, respectively). Formation of the active metabolite occurs via CYP3A4 metabolism. Other enzymes involved in dasatinib metabolism include flavin-containing monooxygenase 3 (FMO-3) and uridine diphosphate-glucuronosyltransferase (UGT). Concentrations of an active metabolite account for about 5% of dasatinib AUC; therefore, the active metabolite is unlikely to play a role in the activity of dasatinib. Several inactive oxidative metabolites are also present. Dasatinib is eliminated primarily via the feces. Following a single dose of radiolabeled dasatinib, 4% of the radioactivity was recovered in the urine and 85% was recovered in the feces within 10 days. Unchanged dasatinib accounted for 0.1% and 19% of the administered dose in the urine and feces, respectively.
     
    Affected cytochrome P450 isoenzymes: CYP3A4
    Dasatinib is extensively metabolized by CYP3A4. Dasatinib is also a weak time-dependent inhibitor of CYP3A4. At clinically relevant concentrations, dasatinib does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP2E1; it does not induce CYP enzymes. In vitro, dasatinib is a substrate for P-glycoprotein (P-gp); it is not a P-gp inhibitor.

    Oral Route

    The Cmax and AUC values were 82.2 ng/mL (coefficient of variance (CV), 69%) and 397 ng/mL x hour (CV, 55%), respectively, following dasatinib 100 mg PO daily. The maximum plasma concentrations occur between 0.5 and 6 hours (Tmax) following oral administration. The adjusted geometric mean Cmax ratio was 0.97 and the adjusted geometric mean AUC ratio was 0.84 in healthy adult subjects who received dasatinib dispersed tablets in juice compared with intact tablets.
    Effects of food: Dasatinib absorption is not significantly affected by food. In subjects who received a single dasatinib 100-mg dose with a high-fat meal (fat, 52%: carbohydrates, 34%; and protein, 14%), the mean AUC increased by 14% compared with fasted subjects.[60087]