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Eribulin MesylatePronunciation: ER-i-BUE-lin MES-i-late
Class: Antineoplastic agent, antimicrotubular
- Injection, solution 0.5 mg/mL
Inhibits the growth phase of microtubules leading to G 2 /M cell-cycle block, disruption of mitotic spindles, and ultimately apoptotic cell death after prolonged mitotic blockage.
Vd is 43 to 114 L/m 2 over a dose range of 0.25 to 4 mg/m 2 . Human plasma protein binding ranged from 49% to 65%.
Metabolized in the liver, predominantly by CYP3A4.
Mean elimination half-life of about 40 h. Mean Cl of 1.16 to 2.42 L/h/m 2 . Eliminated 82% in feces (88% as unchanged) and 9% in urine (91% as unchanged).
Special PopulationsRenal Function Impairment
Patients with moderate renal impairment (CrCl 30 to 50 mL/min) had systemic exposure increased 2-fold; a lower starting dose is recommended. The safety of eribulin was not studied in patients with severe renal impairment (CrCl less than 30 m/min).Hepatic Function Impairment
Exposure increased 1.8-fold and 2.5-fold in patients with mild and moderate hepatic impairment, respectively. A lower starting dose is recommended. Eribulin was not studied in patients with severe hepatic impairment.Elderly
Pharmacokinetics of eribulin were not affected.Gender
Pharmacokinetics of eribulin were not affected.Race
Pharmacokinetics of eribulin were not affected.
Indications and Usage
For the treatment of patients with metastatic breast cancer who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.
None well documented
Dosage and AdministrationMetastatic breast cancer
IV 1.4 mg/m 2 over 2 to 5 min on days 1 and 8 of a 21-day cycle.Dosage adjustment Dose delays
Do not administer on day 1 or day 8 for any of the following: absolute neutrophil count (ANC) less than 1,000/mm 3 , platelets less than 75,000/mm 3 , grade 3 or 4 nonhematological toxicities. The day 8 dose may be delayed for a max of 1 wk. If toxicities do not resolve or improve to grade 2 severity or less by day 15, omit the dose. If toxicities resolve or improve to grade 2 severity or less by day 15, administer eribulin at a reduced dose and initiate the next cycle no sooner than 2 wk later. If a dose has been delayed for toxicity and toxicities have recovered to grade 2 severity or less, resume eribulin at a reduced dose. Do not re-escalate the eribulin dose after it has been reduced.Dose reductions
Permanently reduce the 1.4 mg/m 2 dose to 1.1 mg/m 2 for any of the following: ANC less than 500/mm 3 for more than 7 days, ANC less than 1,000/mm 3 with fever or infection, platelets less than 25,000/mm 3 , platelets less than 50,000/mm 3 requiring transfusion, nonhematologic grade 3 or 4 toxicities, omission or delay of day 8 eribulin dose in previous cycle for toxicity. Occurrence of any event requiring permanent dose reduction while receiving 1.1 mg/m 2 , reduce dose to 0.7 mg/m 2 . Occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m 2 , discontinue eribulin.Renal function impairment Moderate renal impairment (CrCl 30 to 50 mL/min)
1.1 mg/m 2 IV over 2 to 5 min on days 1 and 8 of a 21-day cycle.Hepatic function impairment Mild hepatic impairment (Child-Pugh class A)
1.1 mg/m 2 IV over 2 to 5 min on days 1 and 8 of a 21-day cycle.Moderate hepatic impairment (Child-Pugh class B)
0.7 mg/m 2 IV over 2 to 5 min on days 1 and 8 of a 21-day cycle.
- Administer by IV over 2 to 5 min on days 1 and 8 of a 21-day cycle.
- Withdrawal the required amount from the single-use vial and administer undiluted or diluted in 100 mL of sodium chloride 0.9% injection.
- Do not dilute in or administer through an IV line containing solutions with dextrose.
- Do not administer in the same IV line concurrent with other drug products.
Store vials in original container at 77°F; excursions are permitted between 59° and 86°F. Do not freeze. Store undiluted syringe for up to 4 h at room temperature or for up to 24 h under refrigeration (40°F). Store diluted solutions for up to 4 h at room temperature or up to 24 h under refrigeration. Discard unused portions of the vial.
None well documented.
Asthenia/fatigue (54%); peripheral neuropathy (35%); headache (19%); depression, dizziness, insomnia (5% to less than 10%).
Alopecia (45%); rash (5% to less than 10%).
Nausea (35%); constipation (25%); diarrhea, vomiting (18%); abdominal pain, dry mouth, dyspepsia, stomatitis (5% to less than 10%).
Neutropenia (82%); anemia (58%); febrile neutropenia (5%); thrombocytopenia (1%).
Weight decreased (21%); anorexia (20%); hypokalemia, peripheral edema (5% to less than 10%).
Arthralgia/myalgia (22%); back pain (16%); bone pain (12%); pain in extremity (11%); muscle spasms, muscular weakness (5% to less than 10%).
Dyspnea (16%); cough (14%); upper respiratory tract infection (5% to less than 10%).
Dysgeusia, increased lacrimation (5% to less than 10%).
Pyrexia (21%); increased ALT (18%); UTI (10%); mucosal inflammation (9%).
Assess for peripheral neuropathy and obtain complete blood cell counts prior to each dose. Increase the frequency of monitoring in patients who develop grade 3 or 4 cytopenias. Monitor patients closely for signs of peripheral motor and sensory neuropathy. ECG monitoring is recommended in patients with CHF, bradyarrhythmias, or electrolyte abnormalities, or taking drugs known to prolong the QT interval . Monitor potassium and magnesium prior to and periodically throughout therapy.
Category D . Expected to cause fetal harm.
Safety and efficacy not established.
A lower starting dose is recommended for patients with moderate renal impairment (CrCl 30 to 50 mL/min).
A lower starting dose is recommended for patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment.
Severe neutropenia (ANC less than 500/mm 3 ) lasting more than 1 wk has occurred. Patients with ALT and AST greater than 3 times the ULN also experienced a higher incidence of grade 4 neutropenia and febrile neutropenia.
May occur and was the most common toxicity leading to drug discontinuation.
May occur independent of eribulin concentration. Avoid use in patients with congenital long QT syndrome.
Grade 3 neutropenia and hypersensitivity reaction.
- Advise patients to contact their health care provider if they experience a fever of 100.5°F or more, or other symptoms of infection, such as chills, cough, or burning or pain when urinating.
- Advise women of childbearing potential to avoid pregnancy and to use effective contraception during treatment.
Copyright © 2009 Wolters Kluwer Health.