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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

    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

    Generic:
    - 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.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, geriatric, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    QT prolongation has been reported with eribulin therapy. Do not use eribulin in patients with congenital long QT syndrome. Cautious use and electrocardiogram monitoring are recommended in patients with heart failure, bradyarrhythmias, bradycardia, electrolyte imbalance (e.g., hypocalcemia), and patients receiving medications 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. Use eribulin with caution in patients with conditions that may increase the risk of QT prolongation including AV block, stress-related cardiomyopathy, myocardial infarction, stroke, or in patients receiving medications known to cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) 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/minute) at baseline should receive a reduced initial dose of eribulin; eribulin use in patients with severe renal impairment (CrCl less than 30 mL/minute) 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 / 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.
    Aclidinium; 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.
    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.
    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.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with eribulin. Amisulpride causes dose- and concentration- dependent QT prolongation. Eribulin has been associated with QT prolongation.
    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) Use apomorphine and eribulin together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Eribulin has been associated with QT prolongation. ECG monitoring is recommended if eribulin is administered with apomorphine.
    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) Avoid coadministration of azithromycin with eribulin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Eribulin has been associated with QT prolongation.
    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) Concomitant use of metronidazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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.
    Budesonide; 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.
    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.
    Cabotegravir; 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.
    Ceritinib: (Major) Avoid coadministration of ceritinib with eribulin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs and electrolytes; 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) Avoid coadministration of chloroquine with eribulin due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Eribulin has been associated with QT 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.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciprofloxacin: (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: (Contraindicated) 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.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with eribulin. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Eribulin has been associated with QT 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) Avoid coadministration of crizotinib with eribulin due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Eribulin has also been associated with QT prolongation.
    Dasatinib: (Major) ECG monitoring is recommended if eribulin and dasatinib must be coadministered; closely monitor the patient for QT interval prolongation. Eribulin has been associated with QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
    Degarelix: (Major) ECG monitoring is recommended if eribulin is administered with degarelix. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Deutetrabenazine: (Major) ECG monitoring is recommended if eribulin is administered with deutetrabenazine. The risk of QT prolongation may be increased with coadministration of deutetrabenazine and eribulin. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Eribulin has been associated with QT prolongation.
    Dofetilide: (Major) Coadministration of dofetilide and eribulin is not recommended as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Eribulin has been associated with QT prolongation.
    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.
    Dolutegravir; 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.
    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.
    Dronedarone: (Contraindicated) 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.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (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.
    Encorafenib: (Major) Avoid coadministration of encorafenib and eliglustat due to QT prolongation. If eribulin and encorafenib must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Eribulin has been associated with QT prolongation.
    Entrectinib: (Major) Avoid coadministration of entrectinib with eribulin due to the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended. Both entrectinib and eribulin have been associated with QT prolongation.
    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.
    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.
    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: (Moderate) ECG monitoring is recommended if eribulin is administered with fluoxetine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Eribulin has also been associated with QT 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.
    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.
    Fostemsavir: (Major) ECG monitoring is recommended if eribulin is administered with fostemsavir. Eribulin has been associated with QT prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    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.
    Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and eribulin is necessary. ECG monitoring is recommended. Gilteritinib and eribulin have both been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with eribulin due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Eribulin has also 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) Closely monitor ECGs for QT prolongation if coadministration of eribulin with goserelin is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    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.
    Histrelin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with histrelin is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Hydroxychloroquine: (Major) Avoid coadministration of eribulin and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both hydroxychloroquine and eribulin have been associated with QT prolongation.
    Hydroxyzine: (Major) Monitor ECG if eribulin is administered with hydroxyzine as coadministration may increase the risk for additive QT prolongation and torsade de pointes (TdP). Eribulin has been associated with QT prolongation. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    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.
    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.
    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.
    Ipratropium; 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.
    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.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with eribulin due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Eribulin has been associated with QT prolongation.
    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.
    Lansoprazole; Amoxicillin; 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.
    Lapatinib: (Major) Closely monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with eribulin is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Eribulin has also been associated with QT prolongation.
    Lefamulin: (Major) Avoid coadministration of lefamulin with eribulin as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Eribulin has been associated with QT prolongation.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with eribulin due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Eribulin has also been associated with QT prolongation.
    Leuprolide: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with leuprolide is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with leuprolide is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    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.
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with eribulin due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Eribulin has been associated with QT 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) Avoid coadministration of lopinavir with eribulin due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs are associated with QT prolongation.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as eribulin. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Eribulin has been associated with QT prolongation.
    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.
    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.
    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: (Contraindicated) 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) Concomitant use of metronidazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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: (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.
    Mobocertinib: (Major) Concomitant use of mobocertinib and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) 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.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and eribulin; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Additionally, QT prolongation has occurred with eribulin use.
    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.
    Olanzapine; Fluoxetine: (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. (Moderate) ECG monitoring is recommended if eribulin is administered with fluoxetine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Eribulin has also been associated with QT prolongation.
    Olanzapine; Samidorphan: (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.
    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).
    Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with eribulin. Osilodrostat is associated with dose-dependent QT prolongation. Eribulin has been associated with QT prolongation.
    Osimertinib: (Major) Avoid coadministration of eribulin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. 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.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking eribulin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If concomitant use is necessary, monitor ECGs. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eribulin has been associated with QT prolongation.
    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; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. 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, including eribulin. However, if coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. ECG monitoring is recommended during coadministration.
    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.
    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: (Contraindicated) 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.
    Pitolisant: (Major) Avoid coadministration of pitolisant with eribulin as concurrent use may increase the risk of QT prolongation. If coadministration is necessary, monitor ECG. Eribulin has been associated with QT prolongation. Pitolisant also prolongs the QT interval.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking eribulin due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If treatment initiation is considered, monitor ECGs and for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Eribulin has been associated with QT prolongation.
    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.
    Promethazine; Dextromethorphan: (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.
    Promethazine; Phenylephrine: (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.
    Relugolix: (Major) ECG monitoring is recommended if eribulin is administered with relugolix. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Major) ECG monitoring is recommended if eribulin is administered with relugolix. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    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.
    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.
    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: (Moderate) Monitor ECG if risperidone is coadministered with eribulin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eribulin has also been associated with QT prolongation.
    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: (Major) Avoid administering saquinavir boosted with ritonavir concurrently with eribulin. If no acceptable alternative therapy is available, perform an ECG at baseline and during concomitant therapy. 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). Eribulin has also been associated with QT prolongation.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with eribulin is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Eribulin has been associated with QT prolongation.
    Sertraline: (Major) Monitor ECG if eribulin is adminsitered with sertraline. Eribulin has been associated with QT prolongation. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Short-acting beta-agonists: (Minor) 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.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving eribulin due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Eribulin has been associated with QT prolongation.
    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) Avoid coadministration of sorafenib with eribulin due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Both drugs are associated with QTc 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.
    Sunitinib: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Eribulin has also been associated with QT 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) Closely monitor ECGs for QT prolongation if coadministration of tamoxifen with eribulin is necessary. 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: (Contraindicated) 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.
    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) Avoid coadministration of eribulin with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Eribulin has also been associated with QT prolongation.
    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.
    Triclabendazole: (Major) Monitor ECGs in patients receiving triclabendazole with eribulin. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Eribulin has been associated with QT 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) Closely monitor ECGs for QT prolongation if coadministration of eribulin with triptorelin is necessary. Eribulin has been associated with QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Umeclidinium; Vilanterol: (Moderate) 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) Avoid coadministration of vandetanib with eribulin due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Eribulin has also been associated with QT prolongation.
    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.
    Voclosporin: (Major) Monitor ECG if eribulin is coadministered with voclosporin. Eribulin has been associated with QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
    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: (Major) Concomitant use of ziprasidone and eribulin should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. 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.

    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.