Dosing and uses of Halaven (eribulin)
Adult dosage forms and strengths
intravenous solution
- 1mg/2mL (0.5mg/mL)
Breast Cancer, Metastatic
Indicated for metastatic breast cancer in patients 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
1.4 mg/m² IV infused over 2-5 min on days 1 and 8 of 21-day cycle
Liposarcoma
Indicated for unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen
1.4 mg/m² IV infused over 2-5 min on days 1 and 8 of 21-day cycle
Dosage modifications
Assess for peripheral neuropathy and obtain CBC counts prior to each dose
Recommended dose delays
- Do not administer on Day 1 or Day 8 for any of the following
- ANC <1,000/mm³
- Platelets <75,000/mm³
- Grade 3 or 4 nonhematological toxicities
- The Day 8 dose may be delayed for a maximum of 1 week:
- If toxicities do not resolve or improve to ≤Grade 2 severity by Day 15, omit the dose
- If toxicities resolve or improved to ≤Grade 2 severity by Day 15, administer at a reduced dose and initiate the next cycle no sooner than 2 weeks later
Recommended dose reductions
- If a dose has been delayed for toxicity and then recovered to ≤Grade 2 severity, resume at reduced doses (see below)
- Do not re-escalate once dose has been reduced
- Permanently reduce the 1.4 mg/m² dose to 1.1 mg/m² for any of the following:
- ANC <500/mm³ for >7 days
- ANC <1,000/mm³ with fever or infection
- Platelets <25,000/mm³
- Platelets <50,000/mm³ requiring transfusion
- Nonhematologic Grade 3 or 4 toxicities
- Omission or delay of Day 8 dose in previous cycle for toxicity
- Permanently reduce dose to 0.7 mg/m² for any of the following:
- Occurrence of any event requiring permanent dose reduction while receiving 1.1 mg/m²
- Discontinue
- Occurrence of any event requiring permanent dose reduction while receiving 0.7 mg/m²
Renal impairment
- Moderate-to-severe (CrCl 15-49 mL/min): 1.1 mg/m² IV
Hepatic impairment
- Mild (Child-Pugh A): 1.1 mg/m² IV
- Moderate (Child-Pugh B): 0.7 mg/m² IV
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
No overall differences in safety were observed between elderly and younger patients
See Adult Dosing section
Halaven (eribulin) adverse (side) effects
>10%
Neutropenia (82%)
Anemia (58%)
Asthenia/fatigue (54%)
Alopecia (45%)
Peripheral neuropathy (35%)
Nausea (35%)
Constipation (25%)
Arthralgia/myalgia (22%)
Pyrexia (21%)
Weight loss (21%)
Anorexia (20%)
Headache (19%)
Vomiting (18%)
Diarrhea (18%)
Back pain (16%)
Dyspnea (16%)
Cough (14%)
Bone pain (12%)
Extremity pain (11%)
Urinary tract infection (10%)
1-10%
Increased lacrimation
Dyspepsia
Abdominal pain
Stomatitis
Xerostomia
URI
Hypokalemia
Muscle spasm/weakness
Dysgeusia
Dizziness
Insomnia
Depression
Rash
Postmarketing Reports
Gastrointestinal disorders: Pancreatitis
Blood and lymphatic system disorders: Lymphopenia
Hepatobiliary disorders: Hepatotoxicity
Immune system disorders: Drug hypersensitivity
Infections and infestations: Pneumonia, sepsis/neutropenic sepsis
Metabolism and nutrition disorders: Hypomagnesemia, dehydration
Respiratory, thoracic and mediastinal disorders: Interstitial lung disease
Skin and subcutaneous tissue disorders: Pruritus
Warnings
Contraindications
None known
Cautions
Monitor for peripheral neuropathy before each dose (see Dosage modifications)
Severe neutropenia reported; monitor complete blood counts prior to each dose (see Dosage modifications); increase frequency of monitoring in patients who develop Grade 3 or 4 cytopenias; delay therapy and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days
Delay administration and/or reduce dose if ANC <1,000/m³, platelets <75,000/m³, or for grade 3-4 nonhematological toxicities (see Dosage modifications)
Caution with CHF, bradyarrhythmias, and congenital long QT syndrome (monitor for QT prolongation); correct hypokalemia or hypomagnesemia before administering drug
May cause additive effects when coadministration with other drugs that prolong QT interval (eg, class Ia or III antiarrhythmics, thioridazine, erythromycin)
Based on animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women or males with female partners of reproductive potentiaL
Pregnancy and lactation
Pregnancy
Based on findings from an animal reproduction study and its mechanism of action, can cause fetal harm when administered to a pregnant woman
There are no available data on the use during pregnancy
Animal studies
- In an animal reproduction study, eribulin mesylate caused embryo-fetal toxicity when administered to pregnant rats during organogenesis at doses below the recommended human
Contraception
- Females: Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks following the final dose
- Males: Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3.5 months following the final dose
Infertility
- Based on animal data, may result in damage to male reproductive tissues leading to impaired fertility of unknown duration
Lactation
Unknown whether distributed in breast milk, caution advised; because of the potential for serious adverse reactions in human milk fed infants, a decision should be made whether to discontinue nursing or to discontinue eribulin, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Halaven (eribulin)
Mechanism of action
Microtubule inhibitor; inhibits growth phase of microtubules, leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death
Pharmacokinetics
Half-life elimination: 40 hr
Vd: 43-115 L/m²
Protein Bound: 49-65%
Metabolism: Negligible
Clearance: 1.16-2.42 L/hr
Excretion: Mostly unchanged in feces (82%), urine (9%)
Administration
IV Incompatibilities
Additive: Dextrose
Y-site: Dextrose
IV Compatibilities
Solution: 0.9% NaCL
IV Preparation
Clear, colorless, sterile solution for IV administration
Each vial contains 1 mg of eribulin mesylate as a 0.5 mg/mL solution in ethanol:water (5:95)
IV infusion: Aseptically withdraw dose; may be administered undiluted or diluted (in 0.9% NaCl 100 mL)
Discard unused portion of viaL
IV Administration
May be administered undiluted or diluted (in 0.9% NaCl 100 mL)
Administer over 2-5 minutes
Do not dilute in or administer through IV line contain solutions with dextrose
Do not administer in same IV line concurrent with other medical products
Storage
Store undiluted eribulin in syringe for up to 4 hr at room temperature or for up to 24 hr under refrigeration (40°F or/ 4°C)
Store diluted solutions of eribulin for up to 4 hr at room temperature or up to 24 hr under refrigeration (40°F or/ 4°C)
