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Eribulin Mesylate

Pronunciation: ER-i-BUE-lin MES-i-late
Class: Antineoplastic agent, antimicrotubular

Trade Names

Halaven
- Injection, solution 0.5 mg/mL

Pharmacology

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.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Distribution

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%.

Metabolism

Metabolized in the liver, predominantly by CYP3A4.

Elimination

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 Populations

Renal 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.

Contraindications

None well documented

Dosage and Administration

Metastatic breast cancer
Adults

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.

General Advice

  • 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.

Storage/Stability

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.

Drug Interactions

None well documented.

Adverse Reactions

CNS

Asthenia/fatigue (54%); peripheral neuropathy (35%); headache (19%); depression, dizziness, insomnia (5% to less than 10%).

Dermatologic

Alopecia (45%); rash (5% to less than 10%).

GI

Nausea (35%); constipation (25%); diarrhea, vomiting (18%); abdominal pain, dry mouth, dyspepsia, stomatitis (5% to less than 10%).

Hematologic

Neutropenia (82%); anemia (58%); febrile neutropenia (5%); thrombocytopenia (1%).

Metabolic-Nutritional

Weight decreased (21%); anorexia (20%); hypokalemia, peripheral edema (5% to less than 10%).

Musculoskeletal

Arthralgia/myalgia (22%); back pain (16%); bone pain (12%); pain in extremity (11%); muscle spasms, muscular weakness (5% to less than 10%).

Respiratory

Dyspnea (16%); cough (14%); upper respiratory tract infection (5% to less than 10%).

Special Senses

Dysgeusia, increased lacrimation (5% to less than 10%).

Miscellaneous

Pyrexia (21%); increased ALT (18%); UTI (10%); mucosal inflammation (9%).

Precautions

Monitor

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.


Pregnancy

Category D . Expected to cause fetal harm.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

A lower starting dose is recommended for patients with moderate renal impairment (CrCl 30 to 50 mL/min).

Hepatic Function

A lower starting dose is recommended for patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment.

Neutropenia

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.

Peripheral neuropathy

May occur and was the most common toxicity leading to drug discontinuation.

QT prolongation

May occur independent of eribulin concentration. Avoid use in patients with congenital long QT syndrome.

Overdosage

Symptoms

Grade 3 neutropenia and hypersensitivity reaction.

Patient Information

  • 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.

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