Note: International Considerations: Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific dosing information.
Breast cancer, metastatic: IV: Eribulin mesylate: 1.4 mg/m2 on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity (Cortes 2011).
Liposarcoma, unresectable or metastatic: IV: Eribulin mesylate: 1.4 mg/m2 on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity (Schöffski 2016).
Uterine leiomyosarcoma, refractory (off-label use): IV: Eribulin mesylate: 1.4 mg/m2 on days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity (Schöffski 2016). Refer to protocol for dosage modification details.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: International Considerations: Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific dosing information.
CrCl ≥50 mL/minute: No initial dosage adjustment necessary.
CrCl 15 to 49 mL/minute: Reduce initial dose to eribulin mesylate 1.1 mg/m2.
ESRD (Canadian labeling): Use is not recommended.
Hemodialysis: May consider administering 80% of the original dose (Krens 2019).
Note: International Considerations: Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific dosing information.
Mild hepatic impairment (Child-Pugh class A): Reduce initial dose to eribulin mesylate 1.1 mg/m2.
Moderate hepatic impairment (Child-Pugh class B): Reduce initial dose to eribulin mesylate 0.7 mg/m2.
Severe hepatic impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's US labeling. Use is not recommended (Krens 2019).
Refer to adult dosing.
ASCO Guidelines for appropriate chemotherapy dosing in adults with a BMI ≥30 kg/m2 with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (ASCO [Griggs 2012]).
Note: International Considerations: Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific dosing information.
ANC <1,000/mm3 or platelets <75,000/mm3 or grade 3 or 4 nonhematologic toxicity on day 1 or 8: Withhold dose; may delay day 8 dose up to 1 week. If toxicity resolves to ≤ grade 2 by day 15, administer a reduced dose and wait at least 2 weeks before beginning the next cycle. Omit dose if not resolved to ≤ grade 2 by day 15. Do not re-escalate dose after reduction.
Permanently reduce dose from eribulin mesylate 1.4 mg/m2 to 1.1 mg/m2 for the following:
ANC <500/mm3 for >7 days
ANC <1000/mm3 with fever or infection
Platelets <25,000/mm3
Platelets <50,000/mm3 requiring transfusion
Nonhematologic toxicity of grade 3 or 4
Dose omission or delay due to toxicity on day 8 of prior cycle
Permanently reduce dose from eribulin mesylate 1.1 mg/m2 to 0.7 mg/m2 for occurrence of any of the above events; discontinue treatment if the above toxicities occur at the 0.7 mg/m2 dose level.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as mesylate:
Halaven: 1 mg/2 mL (2 mL) [contains alcohol, usp]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as mesylate:
Halaven: 1 mg/2 mL (2 mL) [contains alcohol, usp]
IV: Infuse over 2 to 5 minutes. May be administered undiluted or diluted. Do not administer other medications through the same IV line, or through a line containing dextrose.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Breast cancer, metastatic: Treatment of metastatic breast cancer in patients who have received at least 2 prior chemotherapy regimens for the treatment of metastatic disease (prior treatment should have included an anthracycline and a taxane in either the adjuvant or metastatic setting).
Liposarcoma, unresectable or metastatic: Treatment of unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen.
Uterine leiomyosarcoma, refractory
EriBULin may be confused with epiRUBicin, erdafitinib, erlotinib, tirbanibulin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific strength and dosing information.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults.
>10%:
Cardiovascular: Peripheral edema (≥5% to 12%)
Dermatologic: Alopecia (35% to 45%)
Endocrine & metabolic: Hypocalcemia (28%), hypokalemia (5% to 30%), hypophosphatemia (20%), weight loss (21%)
Gastrointestinal: Abdominal pain (5% to 29%), anorexia (20%), constipation (25% to 32%), decreased appetite (19%), diarrhea (17% to 18%), nausea (35% to 41%; grades ≥3: 1%), stomatitis (5% to 14%; grades 3/4: <1%), vomiting (18% to 19%; grades ≥3: 1%)
Genitourinary: Urinary tract infection (10% to 11%)
Hematologic & oncologic: Anemia (58% to 70%; grades ≥3: 2% to 4%), neutropenia (63% to 82%; grades ≥3: 12% to 57%)
Hepatic: Increased serum alanine aminotransferase (43%), increased serum aspartate aminotransferase (36%)
Nervous system: Asthenia (≤62%), fatigue (≤62%), headache (18% to 19%), peripheral neuropathy (29% to 35%; grade ≥3: ≤8%; including paresthesia, peripheral motor neuropathy [4%], polyneuropathy, sensorimotor neuropathy)
Neuromuscular & skeletal: Arthralgia (≤22%), back pain (16%), limb pain (11%), myalgia (≤22%), ostealgia (12%)
Respiratory: Cough (14% to 18%), dyspnea (16%)
Miscellaneous: Fever (21% to 28%)
1% to 10%:
Cardiovascular: Hypotension (5% to 10%)
Dermatologic: Skin rash (5% to 10%)
Endocrine & metabolic: Hyperglycemia (5% to 10%)
Gastrointestinal: Dysgeusia (5% to 10%), dyspepsia (5% to 10%), mucosal swelling (9%), xerostomia (5% to 10%)
Hematologic & oncologic: Febrile neutropenia (≤5%), thrombocytopenia (5% to 10%; grades ≥3: 1%)
Nervous system: Anxiety (5% to 10%), depression (5% to 10%), dizziness (5% to 10%), insomnia (5% to 10%), myasthenia (5% to 10%)
Neuromuscular & skeletal: Muscle spasm (5% to 10%), musculoskeletal pain (5% to 10%)
Ophthalmic: Increased lacrimation (5% to 10%)
Respiratory: Oropharyngeal pain (5% to 10%), upper respiratory tract infection (5% to 10%)
Postmarketing:
Cardiovascular: Prolonged QT interval on ECG (Lesimple 2013)
Dermatologic: Pruritus, skin abnormalities related to radiation recall (Tran 2020), Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Dehydration, hypomagnesemia
Gastrointestinal: Pancreatitis
Hematologic & oncologic: Leukopenia (Watanabe 2017), lymphocytopenia (Watanabe 2017), tumor lysis syndrome (Pabon 2018, Tsuchie 2021)
Hepatic: Hepatotoxicity
Hypersensitivity: Hypersensitivity reaction
Infection: Neutropenic sepsis (Lim 2021), sepsis
Nervous system: Encephalopathy (Sheikh 2020)
Respiratory: Hypersensitivity pneumonitis (Murakami 2020), interstitial pulmonary disease (including interstitial pneumonitis) (Murakami 2020, Nakamura 2017), pneumonia, pneumothorax (Takada 2019)
There are no contraindications listed in the manufacturer’s US labeling.
Canadian labeling (not in the US labeling): Hypersensitivity to eribulin mesylate, halichondrin B, or its chemical derivatives.
Concerns related to adverse effects:
• Bone marrow suppression: Hematologic toxicity, including severe neutropenia and neutropenic fever, has occurred. Neutropenic sepsis (fatal) has also been reported (case reports). A higher incidence of grade 4 neutropenia and neutropenic fever occurred in patients with ALT or AST >3 × ULN or bilirubin >1.5 × ULN. Hematologic toxicity may require treatment delay and dosage reduction.
• Peripheral neuropathy: Peripheral neuropathy commonly occurs. Peripheral neuropathy may be prolonged (>1 year in 5% of metastatic breast cancer patients and >60 days in close to 60% of liposarcoma patients); over 60% of liposarcoma patients with peripheral neuropathy had not recovered within a median follow-up of ~6 months in one clinical trial. The median time to the first occurrence of peripheral neuropathy (any severity) in liposarcoma patients was 5 months (range: 3.5 to 9 months). Peripheral neuropathy may require treatment delay or discontinuation.
• QT prolongation: QT prolongation was observed on day 8 of eribulin therapy (in an uncontrolled study). Monitor ECG in patients with heart failure, bradyarrhythmia, with concomitant medication known to prolong the QT interval, or with electrolyte imbalance. Correct hypokalemia and hypomagnesemia prior to treatment; monitor electrolytes periodically during treatment. Avoid use in patients with congenital long QT syndrome.
Other warnings/precautions:
• International issues: Some products available internationally may have vial strength and dosing expressed as the base (instead of as the salt). Refer to prescribing information for specific dosing information.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Patients who may become pregnant should use effective contraception during therapy and for at least 2 weeks after the last eribulin dose. Male patients with partners who may become pregnant should also use effective contraception during therapy and for 3.5 months after the last dose of eribulin.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to eribulin may cause fetal harm.
It is not known if eribulin is present in breast milk.
Due to the potential for serious adverse reactions in the nursing infant, breastfeeding is not recommended by the manufacturer during eribulin treatment and for 2 weeks after the last dose.
CBC with differential prior to each dose (increase frequency with grade 3 or 4 cytopenias); renal and liver function tests; serum electrolytes, including potassium and magnesium. Assess for peripheral neuropathy prior to each dose. Monitor ECG in patients with heart failure, bradyarrhythmia, with concomitant medication known to prolong the QT interval, and electrolyte abnormalities (eg, hypokalemia, hypomagnesemia).
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Eribulin is a non-taxane microtubule inhibitor which is a halichondrin B analog. It inhibits the growth phase of the microtubule by inhibiting formation of mitotic spindles causing mitotic blockage and arresting the cell cycle at the G2/M phase; suppresses microtubule polymerization yet does not affect depolymerization.
Distribution: Vd: 43 to 114 L/m2.
Protein binding: 49% to 65%.
Metabolism: Negligible.
Half-life, elimination: ~40 hours.
Excretion: Feces (~82%, ~88% as unchanged drug); urine (9%, ~91% as unchanged drug).
Clearance: 1.16 to 2.42 L/hour/m2.
Altered kidney function: Patients with moderate or severe renal impairment (CrCl 15 to 49 mL/minute) had systemic exposure increased 1.5-fold compared to patients with normal renal function.
Hepatic function impairment: Exposures increased 1.8-fold and 2.5-fold in patients with mild and moderate hepatic impairment, respectively, compared to patients with normal hepatic function.
Solution (Halaven Intravenous)
1 mg/2 mL (per mL): $777.60
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