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  • CLASSES

    Other Antineoplastic Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Non-taxane, microtubule dynamics inhibitor
    Indicated for metastatic breast cancer in patients who have previously received at least 2 chemotherapeutic regimens and for unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen
    QT prolongation has been reported

    COMMON BRAND NAMES

    Halaven

    HOW SUPPLIED

    Halaven Intravenous Inj Sol: 0.5mg, 1mL

    DOSAGE & INDICATIONS

    For the treatment of patients with breast cancer.
    For the treatment of metastatic breast cancer in patients who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease, including both an anthracycline and a taxane in either the adjuvant or metastatic setting.
    Intravenous dosage
    Adults

    1.4 mg/m2 IV over 2 to 5 minutes on days 1 and 8; treatment cycles are repeated every 21 days until disease progression. Do not administer eribulin on day 1 or day 8 if the absolute neutrophil count is less than 1,000 cells/mm3, the platelet count is less than 75,000 cells/mm3, or a patient has a grade 3 or 4 non-hematological toxicity. Therapy interruption, dose reduction, or discontinuation may be necessary in patients who develop severe toxicity. In a clinical trial, 762 patients were randomized 2:1 to receive eribulin or another single-agent (vinorelbine 26%, gemcitabine 18%, capecitabine 18%, taxane 16%, anthracycline 9%, other 10%). The primary endpoint, overall survival, was significantly longer in patients who received eribulin (13.2 months vs. 10.6 months, p = 0.041). The objective response rate was 11% in patients who received eribulin, and the median duration of response was 4.2 months. Patients in both arms of the trial had previously received a median of 4 prior chemotherapy regimens.

    For the treatment of soft-tissue sarcoma.
    Eribulin has been designated by the FDA as an orphan drug for the treatment of advanced soft-tissue sarcoma.
    For the treatment of unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen.
    Intravenous dosage
    Adults

    1.4 mg/m2 IV over 2 to 5 minutes on days 1 and 8; treatment cycles are repeated every 21 days until disease progression. Do not administer eribulin on day 1 or day 8 if the absolute neutrophil count is less than 1,000 cells/mm3, the platelet count is less than 75,000 cells/mm3, or a patient has a grade 3 or 4 non-hematological toxicity. Therapy interruption, dose reduction, or discontinuation may be necessary in patients who develop severe toxicity. In a multinational, randomized, phase III trial (n = 452), the median overall survival (OS) time (primary endpoint) was significantly improved with eribulin compared with dacarbazine (13.5 months vs. 11.5 months; hazard ratio (HR) = 0.77; 95% CI, 0.62 to 0.95; p = 0.0169) in patients with high or intermediate grade, unresectable, locally advanced or metastatic liposarcoma or leiomyosarcoma who had received at least 2 prior systemic chemotherapy regimens (including an anthracycline). The median follow-up time for overall survival was 31 months. The median OS time was significantly improved with eribulin compared with dacarbazine therapy in 143 patients who had liposarcoma (15.6 months vs. 8.4 months; HR = 0.51; 95% CI, 0.35 to 0.75) but not in 309 patients who had leiomyosarcoma (12.7 months vs. 13 months; HR = 0.93; 95% CI, 0.71 to 1.2). The median progression-free survival time was 2.6 months in both treatment arms.

    MAXIMUM DOSAGE

    Adults

    1.4 mg/m2 IV.

    Geriatric

    1.4 mg/m2 IV.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment
    Mild hepatic impairment (Child-Pugh A): Decrease starting dose to 1.1 mg/m2 IV.
    Moderate hepatic impairment (Child-Pugh B): Decrease starting dose to 0.7 mg/m2 IV.
    Severe hepatic impairment (Child-Pugh C): Not studied.
    Treatment-Induced Hepatotoxicity
    Grade 3 or higher hepatic impairment (total bilirubin greater than 3 times the upper limit of normal (ULN) or ALT/AST greater than 5 times ULN): Hold treatment with eribulin. If toxicities improve to grade 2 or less (total bilirubin greater than 1.5 to 3 times ULN or ALT/AST greater than 3 to 5 times ULN) by day 15, administer eribulin at a reduced dose (reduce dose of 1.4 mg/m2 to 1.1 mg/m2 IV; reduce dose of 1.1 mg/m2 to 0.7 mg/m2 IV) and start the next cycle of therapy no sooner than 2 weeks later. If toxicities do not improve to grade 2 or less by day 15, omit the dose. Discontinue eribulin if grade 3 or higher hepatic impairment occurs at a dose of 0.7 mg/m2; do not re-escalate eribulin dose after it has been reduced.

    Renal Impairment

    Baseline Renal Impairment
    CrCl greater than or equal to 50 mL/min: No dosage adjustments are necessary.
    CrCl 15 to 49 mL/min: Decrease starting dose to 1.1 mg/m2 IV.
    CrCl less than 15 mL/min: Not studied.
    Treatment-Induced Nephrotoxicity
    Grade 3 or higher renal impairment (SCr greater than 3 times baseline, or greater than 4 mg/dL; hospitalization indicated): Hold treatment with eribulin. If toxicities improve to grade 2 or less (SCr 2 to 3 times baseline) by day 15, administer eribulin at a reduced dose (reduce dose of 1.4 mg/m2 to 1.1 mg/m2 IV; reduce dose of 1.1 mg/m2 to 0.7 mg/m2 IV) and start the next cycle of therapy no sooner than 2 weeks later. If toxicities do not improve to grade 2 or less by day 15, omit the dose. Discontinue eribulin if grade 3 or higher renal impairment occurs at a dose of 0.7 mg/m2; do not re-escalate eribulin dose after it has been reduced.

    ADMINISTRATION

     
    CAUTION: Observe and exercise usual precautions for handling, preparing, and administering solutions of cytotoxic drugs.

    Injectable Administration

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

    Intravenous Administration

    Withdraw the required amount of eribulin (0.5 mg/mL) from the single-use vial.
    May administer undiluted in a syringe or dilute in 100 mL 0.9% Sodium Chloride Injection.
    Administer intravenously over 2 to 5 minutes as a slow IV push or intermittent infusion.
    Do not dilute in or administer through an intravenous line containing solutions with dextrose.
    Do not administer in the same intravenous line concurrent with other products.
    Undiluted eribulin in a syringe and diluted eribulin solutions are stable for 4 hours at room temperature or 24 hours under refrigeration (4 degrees C or 40 degrees F).

    STORAGE

    Halaven:
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in carton

    CONTRAINDICATIONS / PRECAUTIONS

    Neutropenia, thrombocytopenia

    Hematologic toxicity including neutropenia, febrile neutropenia, and thrombocytopenia has been reported with eribulin therapy; fatal neutropenic sepsis has occurred. Monitor complete blood counts prior to each eribulin dose and more frequently in patients with grade 3 or 4 toxicity. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe hematologic toxicity. In a study in patients with metastatic breast cancer, the mean time to neutrophil nadir following eribulin therapy was 13 days; time to recovery following severe neutropenia (less than 500 cells/mm3) was 8 days. Patients with a baseline absolute neutrophil counts less than 1,500 cells/mm3 were not included in clinical trials.

    Peripheral neuropathy

    Peripheral neuropathy has been reported with eribulin therapy. Monitor patients for signs of peripheral motor and sensory neuropathy prior to each eribulin dose. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe neuropathy.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, geriatric, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    QT prolongation has been reported with eribulin therapy. Electrocardiogram monitoring is recommended in patients with congestive heart failure, bradyarrhythmias/bradycardia, electrolyte imbalance, and patients receiving drugs known to prolong the QT interval, including class Ia and III antiarrhythmic agents. Correct hypokalemia and hypomagnesemia prior to starting eribulin; monitor electrolytes periodically during therapy. Do not use eribulin in patients with congenital long QT syndrome. Furthermore, use eribulin with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, myocardial infarction, hypertension, coronary artery disease, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation.

    Hepatic disease, hepatotoxicity

    Hepatotoxicity has been reported with eribulin therapy. Patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment/hepatic disease at baseline should receive a reduced initial dose of eribulin; eribulin use in patients with severe hepatic impairment (Child-Pugh C) has not been studied. Metastatic breast cancer patients with elevated transaminase levels (greater than 3 times the upper limit of normal (ULN)) or hyperbilirubinemia (greater than 1.5 times the ULN) had a higher incidence of grade 4 neutropenia and febrile neutropenia compared with patients who had normal hepatic function in a clinical study.

    Renal disease, renal impairment

    Use eribulin with caution in patients with renal disease. Patients with moderate renal impairment (creatinine clearance (CrCl), 30 to 50 mL/min) at baseline should receive a reduced initial dose of eribulin; eribulin use in patients with severe renal impairment (CrCl < 30 mL/min) has not been studied.

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

    Counsel patients about the reproductive risk and contraception requirements during eribulin treatment. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 2 weeks after the last dose of eribulin. Due to the potential for male-mediated teratogenicity, men with female partners should avoid fathering a child and use effective contraception during and for at least 3.5 months following completion of eribulin therapy. Infertility may occur in men who receive eribulin therapy based on animal data. Testicular toxicity (hypocellularity of seminiferous epithelium with hypospermia/aspermia) was observed in rats and dogs who received eribulin doses that were lower than the recommended human dose.

    Pregnancy

    Eribulin may cause fetal harm during pregnancy based on its mechanism of action and findings from animal reproduction studies. Advise females of reproductive potential to avoid becoming pregnant while taking eribulin. Women who become pregnant while receiving eribulin should be apprised of the potential hazard to the fetus. Increased abortion rates and severe fetal external or soft tissue malformations (e.g., absence of a lower jaw and tongue or of the stomach and spleen) were observed in pregnant rats who received eribulin doses approximately 0.64-times the recommended human dose of 1.4 mg/m2. Additionally, increased embryo-fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay were reported at eribulin doses approximately 0.43-times the recommended human dose.

    Breast-feeding

    Avoid breast-feeding during treatment with eribulin and for 2 weeks after the final dose due to the potential for serious adverse reactions in breast-fed infants from eribulin. It is not known if eribulin mesylate is secreted in human milk or if it affects the breast-fed infant or milk production.

    ADVERSE REACTIONS

    Severe

    neutropenia / Delayed / 32.0-57.0
    asthenia / Delayed / 0-10.0
    fatigue / Early / 0-10.0
    peripheral neuropathy / Delayed / 3.1-8.0
    paresthesias / Delayed / 0-8.0
    hypokalemia / Delayed / 0-5.4
    hypocalcemia / Delayed / 0-5.0
    anemia / Delayed / 2.0-4.1
    dyspnea / Early / 4.0-4.0
    hypophosphatemia / Delayed / 0-3.2
    infection / Delayed / 1.0-2.2
    bone pain / Delayed / 0-2.0
    abdominal pain / Early / 0-1.8
    headache / Early / 0-1.0
    thrombocytopenia / Delayed / 1.0-1.0
    anorexia / Delayed / 1.0-1.0
    vomiting / Early / 0-1.0
    constipation / Delayed / 0.9-1.0
    nausea / Early / 0-1.0
    myalgia / Early / 0-1.0
    arthralgia / Delayed / 0-1.0
    back pain / Delayed / 0-1.0
    fever / Early / 0-1.0
    weight loss / Delayed / 1.0-1.0
    stomatitis / Delayed / 0-0.9
    elevated hepatic enzymes / Delayed / 0.9
    pancreatitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 5.0-12.0
    depression / Delayed / 5.0-9.9
    hypotension / Rapid / 5.0-9.9
    hyperglycemia / Delayed / 5.0-9.9
    hyperbilirubinemia / Delayed / 0-1.0
    lymphopenia / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    dehydration / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known

    Mild

    alopecia / Delayed / 35.0-45.0
    diarrhea / Early / 17.0-18.0
    cough / Delayed / 14.0-18.0
    dysgeusia / Early / 5.0-9.9
    dizziness / Early / 5.0-9.9
    xerosis / Delayed / 5.0-9.9
    dyspepsia / Early / 5.0-9.9
    muscle cramps / Delayed / 5.0-9.9
    musculoskeletal pain / Early / 5.0-9.9
    weakness / Early / 5.0-9.9
    rash (unspecified) / Early / 5.0-9.9
    lacrimation / Early / 5.0-9.9
    insomnia / Early / 5.0-9.9
    anxiety / Delayed / 5.0-9.9
    pruritus / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include abarelix.
    Albuterol: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Alfuzosin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as alfuzosin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Eribulin has been associated with QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. If eribulin and amiodarone must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include clarithromycin.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include clarithromycin.
    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 eribulin.
    Apomorphine: (Major) Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. In one study, a single mean dose of 5.2 mg (range 2-10 mg) prolonged the QT interval by about 3 msec. However, large increases (> 60 msecs from pre-dose) have occurred in two patients receiving 6 mg doses. Doses <= 6 mg SC are associated with minimal increases in QTc; doses > 6 mg SC do not provide additional clinical benefit and are not recommended. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with apomorphine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Arformoterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    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 eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Artemether; Lumefantrine: (Major) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be avoided with artemether; lumefantrine include eribulin. If eribulin and another drug that prolongs the QT interval, such as artemether; lumefantrine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be avoided in combination with asenapine include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Atomoxetine: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include eribulin.
    Azithromycin: (Major) Concurrent use of eribulin and azithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the use of azithromycin during the post-marketing period.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with eribulin. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline electrocardiogram (ECG). An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include eribulin.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include eribulin.
    Budesonide; Formoterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with eribulin. Eribulin has been associated with QT prolongation. Buprenorphine has also 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. If eribulin and buprenorphine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with eribulin. Eribulin has been associated with QT prolongation. Buprenorphine has also 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. If eribulin and buprenorphine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ceritinib: (Major) Closely monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and eribulin; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Eribulin is also associated with QT prolongation.
    Chloroquine: (Major) Chloroquine administration is associated with an increased risk of QT prolongation and torsades de pointes (TdP). The need to coadminister chloroquine with drugs known to prolong the QT interval should be done with a careful assessment of risks versus benefits and should be avoided when possible. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with chloroquine include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Chlorpromazine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP ; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used with caution with chlorpromazine include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ciprofloxacin: (Major) Concurrent use of eribulin and ciprofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation, and ciprofloxacin is associated with a posssible risk for QT prolongation and TdP.
    Cisapride: (Severe) Eribulin has been associated with QT prolongation. Cisapride has been specifically established to have a causal association with QT prolongation and torsade de pointes and is contraindicated for use with eribulin.
    Citalopram: (Major) Citalopram causes dose-dependent QT interval prolongation. Eribulin is associated with a possible risk for QT prolongation and TdP (torsade de pointes). According to the manufacturer of citalopram, 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; closely monitor the patient for QT interval prolongation.
    Clarithromycin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include clarithromycin.
    Class IA Antiarrhythmics: (Major) Eribulin has been associated with QT prolongation. Class IA antiarrhythmics (disopyramide, procainamide, quinidine) are associated with QT prolongation and torsades de pointes (TdP). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with clozapine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with eribulin. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Both drugs have independently been associated with QT prolongation.
    Cyclobenzaprine: (Major) Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have been reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). Cyclobenzaprine is associated with a possible risk of QT prolongation and torsades de pointes (TdP), particularly in the event of acute overdose. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with cyclobenzaprine include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include eribulin.
    Dasatinib: (Major) 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with dasatinib include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Daunorubicin: (Major) Eribulin has been associated with QT prolongation. If eribulin and daunorubicin must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Acute cardiotoxicity can occur during the administration of daunorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Degarelix: (Major) Since degarelix can cause QT prolongation, degarelix should be used cautiously with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of degarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with degarelix include eribulin.
    Deutetrabenazine: (Major) If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. For patients taking a deutetrabenazine dosage more than 24 mg/day with eribulin, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Eribulin has been associated with QT prolongation.
    Dextromethorphan; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    Diclofenac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as diclofenac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Diclofenac; Misoprostol: (Minor) An increased risk of bleeding may occur when NSAIDs, such as diclofenac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Diphenhydramine; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Diphenhydramine; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Dofetilide: (Severe) Eribulin has been associated with QT prolongation. Because of the potential for torsades de pointes (TdP), use of dofetilide with eribulin is contraindicated.
    Dolasetron: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with dolasetron include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include eribulin.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include eribulin.
    Doxorubicin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Monitor patients closely for QT prolongation. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Dronedarone: (Severe) Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. Contraindicated drugs inclue dronedarone.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Efavirenz: (Major) Although data are limited, coadministration of efavirenz and eribulin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Eribulin has also been associated with QT prolongation. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and eribulin may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Eribulin has also been associated with QT prolongation. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include eribulin.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Epirubicin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering eribulin with epirubicin. If these drugs must be coadministered, ECG monitoring is recommended. Monitor patients closely for QT prolongation. Eribulin has been associated with QT prolongation. Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Erythromycin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as erythromycin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erythromycin; Sulfisoxazole: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as erythromycin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as eribulin, should be done with caution and close monitoring.
    Esomeprazole; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ester local anesthetics: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as local anesthetics, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Etodolac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as etodolac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ezogabine: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include ezogabine.
    Famotidine; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Fenoprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as fenoprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Fingolimod: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Eribulin has been associated with QT prolongation. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Flecainide: (Major) Flecainide should be used cautiously and with close monitoring with eribulin. Eribulin has been associated with QT prolongation. If eribulin and flecainide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. 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.
    Fluconazole: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include fluconazole.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include eribulin.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include eribulin. (Major) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with olanzapine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Fluphenazine: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as fluphenazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Flurbiprofen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as flurbiprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Fluticasone; Salmeterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Vilanterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and eribulin. Eribulin has been associated with QT prolongation. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. If eribulin and fluvoxamine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Formoterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as eribulin. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Eribulin has also been associated with QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gemifloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering eribulin with gemifloxacin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both gemifloxacin and eribulin have been associated with QT prolongation. 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: (Major) Use gemtuzumab ozogamicin and eribulin together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Eribulin has been associated with QT prolongation.
    Glycopyrrolate; Formoterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Goserelin: (Major) Eribulin has been associated with QT prolongation. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. If eribulin and goserelin must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Granisetron: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include granisetron.
    Halogenated Anesthetics: (Major) Eribulin and halogenated anesthetics have been associated with QT prolongation. If eribulin must be coadministered with a halogenated anesthetic, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Haloperidol: (Major) QT prolongation and torsade de pointes (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. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval, including eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Hydrocodone; Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and eribulin. 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. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include eribulin.
    Ibuprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ibuprofen; Oxycodone: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ibuprofen; Pseudoephedrine: (Major) An increased risk of bleeding may occur when NSAIDs, such as ibuprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ibutilide include eribulin. If eribulin and and ibutilide are coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Idarubicin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Monitor patients closely for QT prolongation. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation and TdP that should be avoided with iloperidone include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Indacaterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indomethacin: (Major) An increased risk of bleeding may occur when NSAIDs, such as indomethacin, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with eribulin 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; closely monitor the patient for QT interval prolongation. Both inotuzumab and eribulin have been associated with QT prolongation.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include eribulin.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include eribulin.
    Ketoprofen: (Major) An increased risk of bleeding may occur when NSAIDs, such as ketoprofen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Ketorolac: (Major) An increased risk of bleeding may occur when NSAIDs, such as ketorolac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Lansoprazole; Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Lapatinib: (Major) Lapatinib can prolong the QT interval. Lapatinib should be administered with caution to patients who have or may develop prolongation of QTc such as patients taking anti-arrhythmic medicines or other medicinal products that lead to QT prolongation. Administer lapatinib with caution in patients taking drugs with the potential to induce QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with lapatinib include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Lenvatinib: (Major) If eribulin and another drug that prolongs the QT interval, such as lenvatinib, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include eribulin.
    Leuprolide; Norethindrone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include eribulin.
    Levalbuterol: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levofloxacin: (Major) Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of torsade de pointes (TdP) have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. According to the manufacturer, levofloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Lithium: (Major) Lithium should be used cautiously and with close monitoring with eribulin. Lithium has been associated with QT prolongation. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Long-acting beta-agonists: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Eribulin has also been associated with QT prolongation. If eribulin and loperamide must be coadministered, ECG monitoring is recommended.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Eribulin has also been associated with QT prolongation. If eribulin and loperamide must be coadministered, ECG monitoring is recommended.
    Lopinavir; Ritonavir: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as lopinavir; ritonavir, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include eribulin.
    Maprotiline: (Major) 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with maprotiline include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Meclofenamate Sodium: (Major) An increased risk of bleeding may occur when NSAIDs, such as meclofenamate, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Mefenamic Acid: (Major) An increased risk of bleeding may occur when NSAIDs, such as mefenamic acid, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Mefloquine: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as mefloquine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Meloxicam: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, meloxicam may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential.
    Meperidine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    Mesoridazine: (Severe) Eribulin has been associated with QT prolongation. Mesoridazine has been specifically established to have a causal association with QT prolongation and torsade de pointes and are contraindicated for use with eribulin.
    Metaproterenol: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Methadone: (Major) 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with methadone include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include eribulin.
    Midostaurin: (Major) The concomitant use of midostaurin and eribulin may lead to additive QT interval prolongation. If these drugs are used together, monitor electrocardiograms and observe patients closely for QT interval prolongation. Additionally, correct hypokalemia and hypomagnesemia prior to starting eribulin; monitor electrolytes periodically during 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.
    Mifepristone, RU-486: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and eribulin should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Mirtazapine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and eribulin. Coadminister with caution. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine. The majority of reports have occurred in the setting of mirtazapine overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Eribulin has been associated with QT prolongation. If eribulin and mirtazapine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Moxifloxacin: (Major) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP include eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Nabumetone: (Minor) An increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. However, nabumetone may be associated with less risk than other NSAIDs due to its relative minimal platelet inhibitory effects and gastric ulceration or hemorrhagic potential. Monitor closely for bleeding.
    Naproxen: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Naproxen; Pseudoephedrine: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Naproxen; Sumatriptan: (Minor) An increased risk of bleeding may occur when NSAIDs, such as naproxen, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Nilotinib: (Major) Coadministration of nilotinib and a drug that prolongs the QT interval is not advised; nilotinib prolongs the QT interval. If concurrent administration is unavoidable, the manufacturer of nilotinib recommends interruption of nilotinib treatment. If nilotinib must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be avoided in combination with nilotinib include eribulin.
    Norfloxacin: (Major) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with norfloxacin include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Octreotide: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ofloxacin: (Major) Some quinolones, including ofloxacin, have been associated with QT prolongation and infrequent cases of arrhythmia. Post-marketing surveillance for ofloxacin has identified very rare cases of torsades de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ofloxacin include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Olanzapine: (Major) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with olanzapine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Olodaterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include eribulin.
    Ondansetron: (Major) If eribulin and ondansetron must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
    Osimertinib: (Major) Closely monitor electrolytes and ECGs for QT prolongation if coadministration of osimertinib with eribulin is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, and eribulin has also been associated with QT prolongation.
    Oxaliplatin: (Major) Closely monitor ECGs for QT prolongation and monitor electrolytes if coadministration of eribulin with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Eribulin has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience.
    Oxaprozin: (Minor) An increased risk of bleeding may occur when NSAIDs, such as oxaprozin, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. However, if coadministration is considered necessary by the practitioner, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include eribulin.
    Pasireotide: (Major) Eribulin has been associated with QT prolongation. If eribulin and pasireotide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Coadministration may have additive effects on the prolongation of the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as eribulin, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and eribulin must be continued, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentamidine: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include pentamidine.
    Perphenazine: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as perphenazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Perphenazine; Amitriptyline: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as perphenazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    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 eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of eribulin with pimozide is contraindicated.
    Pirbuterol: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Piroxicam: (Minor) An increased risk of bleeding may occur when NSAIDs, such as piroxicam, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Posaconazole: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include posaconazole.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include eribulin.
    Prochlorperazine: (Minor) Phenothiazines have been reported to prolong the QT interval. Concurrent use of drugs that are associated with a possible risk for QT prolongation and torsade de pointes (TdP) with prochlorperazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include eribulin.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with eribulin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation. Propafenone, a Class IC antiarrhythmic, also increases the QT interval, but largely due to prolongation of the QRS interval.
    Quetiapine: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as eribulin. If coadministration is necessary, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Quinine: (Major) Concurrent use of quinine and eribulin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Eribulin has also been associated with QT prolongation.
    Ranolazine: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as ranolazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Regadenoson: (Major) Regadenoson has been associated with QT prolongation. If regadenoson is coadministered with another drug that may prolong the QT interval, such as eribulin, ECG monitoring is recommended. Closely monitor the patient for QT interval prolongation.
    Ribociclib: (Major) Avoid coadministration of ribociclib with eribulin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; eribulin has also been associated with QT prolongation. If eribulin and ribociclib must be coadministered, ECG monitoring is recommended.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with eribulin due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner; eribulin has also been associated with QT prolongation. If eribulin and ribociclib must be coadministered, ECG monitoring is recommended.
    Rilpivirine: (Major) Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval, such as eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, such as eribulin, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include eribulin.
    Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with romidepsin include eribulin.
    Salmeterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Saquinavir: (Severe) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as eribulin. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
    Sertraline: (Major) There have been post-marketing reports of QT prolongation and Torsade de Pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sertraline include eribulin.
    Short-acting beta-agonists: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and antineoplastic agents should be avoided. Concurrent administration of antineoplastic agents with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving antineoplastic agents may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of antineoplastic agents prior to initiating therapy with sipuleucel-T.
    Solifenacin: (Major) Solifenacin should be used cautiously and with close monitoring with eribulin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Eribulin has been associated with QT prolongation. If eribulin and solifenacin must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Sorafenib: (Major) Sorafenib has been associated with QT prolongation. Eribulin is associated with a possible risk for QT prolongation and torsade de pointes. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sotalol include eribulin. If eribulin and sotalol must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include eribulin.
    Sulindac: (Minor) An increased risk of bleeding may occur when NSAIDs, such as sulindac, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Sunitinib: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as sunitinib, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Tacrolimus: (Major) Eribulin has been associated with QT prolongation. Tacrolimus causes QT prolongation. Reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended when coadministrating tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval such as eribulin.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and eribulin due to an increased risk of QT prolongation. If coadministration is needed, ECG monitoring is recommended; closely monitor the patient for QT interval 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. Eribulin has also been associated with QT prolongation.
    Telavancin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as telavancin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Telithromycin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as telithromycin, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Terbutaline: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with tetrabenazine include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Thioridazine: (Severe) Eribulin has been associated with QT prolongation. Thioridazine has been specifically established to have a causal association with QT prolongation and torsade de pointes and is contraindicated for use with eribulin.
    Tiotropium; Olodaterol: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tizanidine: (Major) If eribulin and tizanidine must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Both eribulin and tizanidine have been associated with QT prolongation. Coadministration increases the risk for QT prolongation and torsade de pointes.
    Tolmetin: (Minor) An increased risk of bleeding may occur when NSAIDs, such as tolmetin, are used with agents that cause clinically significant thrombocytopenia, such as myelosuppressive antineoplastic agents. Monitor closely for bleeding.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with eribulin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Eribulin has also been associated with QT prolongation.
    Toremifene: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include toremifene.
    Trazodone: (Major) Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval, such as eribulin. Eribulin has been associated with QT prolongation. If eribulin and trazodone must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Tricyclic antidepressants: (Minor) Tricyclic antidepressants should be used cautiously and with close monitoring with eribulin. Eribulin has been associated with QT prolongation. 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). If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Trifluoperazine: (Minor) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as trifluoperazine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include eribulin.
    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) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; eribulin has also been associated with QT prolongation. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vardenafil include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Eribulin has been associated with QT prolongation. If vemurafenib and another drug that potentially prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Venlafaxine: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as venlafaxine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with eribulin. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Eribulin has also been associated with QT prolongation.
    Vorinostat: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as vorinostat, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including eribulin.

    PREGNANCY AND LACTATION

    Pregnancy

    Eribulin may cause fetal harm during pregnancy based on its mechanism of action and findings from animal reproduction studies. Advise females of reproductive potential to avoid becoming pregnant while taking eribulin. Women who become pregnant while receiving eribulin should be apprised of the potential hazard to the fetus. Increased abortion rates and severe fetal external or soft tissue malformations (e.g., absence of a lower jaw and tongue or of the stomach and spleen) were observed in pregnant rats who received eribulin doses approximately 0.64-times the recommended human dose of 1.4 mg/m2. Additionally, increased embryo-fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay were reported at eribulin doses approximately 0.43-times the recommended human dose.

    Avoid breast-feeding during treatment with eribulin and for 2 weeks after the final dose due to the potential for serious adverse reactions in breast-fed infants from eribulin. It is not known if eribulin mesylate is secreted in human milk or if it affects the breast-fed infant or milk production.

    MECHANISM OF ACTION

    Eribulin is a synthetic macrocyclic ketone analog of the naturally occurring macrolide halichondrin B, which is isolated from the marine sponge Halichondrai okadai. It is a potent antimitotic agent, with a distinct mechanism from other known antimitotic agents, such as taxanes, vinca alkaloids, and epothilones. Eribulin blocks cell cycle progression in the G2-M phase. It inhibits the growth phase of microtubules and sequesters tubulin in nonproductive aggregates, ultimately leading to disruption of mitotic spindles and apoptotic cell death after prolonged mitotic blockage. It accomplishes this primarily by disrupting the complex growth and shortening events of microtubules known as dynamic instability. Eribulin suppresses microtubule growth parameters at plus ends without a significant impact on shortening parameters at minus ends. This prevents the addition of tubulin dimers to the growing end of microtubules. The beta-tubulin subunit, which is exposed at the plus ends of microtubules, contains the major portion of the eribulin binding site. Dynamic instability is critical to the normal assembly and function of the mitotic spindle and subsequent cell proliferation. Dynamically unstable microtubules are necessary for the attachment of chromosomes to the mitotic spindle, for proper alignment of chromosomes at metaphase, and for signaling and induction for their separation at anaphase. The suppression of microtubule dynamics by eribulin, and subsequent prolonged mitotic blockage, leads to apoptotic cell death. Additionally, eribulin causes changes in morphology and gene expression, as well as decreased migration and invasiveness in vitro with human breast cancer cells. In mouse xenograft models of human breast cancer, eribulin treatment was associated with increased vascular perfusion and permeabilitly in the tumor cores, resulting in reduced tumor hypoxia, and changes in the expression of genes in tumor specimens associated with a change in phenotype.

    PHARMACOKINETICS

    Eribulin mesylate is administered intravenously. It has a mean volume of distribution of 43 to 114 L/m2 and human plasma protein binding ranges from 49 to 65%. There are no major metabolites. Unchanged eribulin was the major circulating species after the administration of radiolabeled eribulin to patients. Elimination occurs primarily as unchanged drug through the feces (82%), with a small amount excreted in the urine (9%). It has a mean elimination half-life of approximately 40 hours, with a mean clearance of 1.16 to 2.42 L/hr/m2 over the dose range 0.25 to 4 mg/m2.
     
    Affected cytochrome P450 isoenzymes and drug transporter: CYP3A4, P-gp
    Eribulin is minimally (< 0.6%) metabolized by CYP3A4 in vitro. Based on pharmacokinetic studies with rifampin and ketoconazole, drug interactions are not expected with CYP3A4 inhibitors or inducers. It inhibits CYP3A4 activity in human liver microsomes, but it is unlikely that this will increase exposure of CYP3A4 substrates. Eribulin is also a P-glycoprotein (P-gp) substrate and inhibitor in vitro, but this is also unlikely to result in drug interactions. Additionally, eribulin is not expected to affect plasma levels of drugs that are substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP2E1.

    Intravenous Route

    Total eribulin exposure after multiple dosing is similar to that following a single dose; no accumulation of eribulin is observed with weekly administration.