Halaven (Intravenous)

Uses

Halaven (Intravenous) Mesylate is used for the treatment of patients with metastatic breast cancer who have previously received at least two 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.
Pediatric Use: The safety and effectiveness of Halaven (Intravenous) in pediatric patients below the age of 18 years have not been established.

Geriatric Use: Study 1 did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 827 subjects who received the recommended dose and schedule of Halaven (Intravenous) in clinical studies, 15% (121/827) were 65 and older, and 2% (17/827) patients were 75 and older. No overall differences in safety were observed between these subjects and younger subjects.

Hepatic Impairment: A lower starting dose is recommended for patients with mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment. Patients with severe hepatic impairment (Child-Pugh C) were not studied.

Renal Impairment: A lower starting dose is recommended for patients with moderate (CrCl 30-50 mL/min) renal impairment. Patients with severe (CrCl < 30 mL/min) renal impairment were not studied.

Halaven (Intravenous) is also used to associated treatment for these conditions: Metastatic Liposarcoma, Refractory, metastatic Breast cancer, Unresectable Liposarcoma

How Halaven (Intravenous) works

Halaven (Intravenous) inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Halaven (Intravenous) exerts its effects via a tubulin-based antimitotic mechanism leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. [FDA]

Dosage

Halaven (Intravenous) dosage

The recommended dose of Halaven (Intravenous) Mesylate is 1.4 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of Halaven (Intravenous) Mesylate in patients with mild hepatic impairment (Child-Pugh A) is 1.1 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of Halaven (Intravenous) Mesylate in patients with moderate hepatic impairment (Child-Pugh B) is 0.7 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

The recommended dose of Halaven (Intravenous) Mesylate in patients with moderate renal impairment (creatinine clearance of 30-50 mL/min) is 1.1 mg/m² administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.

Side Effects

The most common adverse reactions (incidence ≥25%) were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation.

Toxicity

Peripheral neuropathy was the most common toxicity leading to discontinuation of eribulin (5 percent). [Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.] Single doses of 0.75 mg/kg were lethal to rats and two doses of 0.075 mg/kg were lethal to dogs. The no-observed-adverse-effect level (NOAEL) in rats and dogs were 0.015 and 0.0045 mg/kg/day, respectively.

Precaution

Neutropenia: Monitor peripheral blood cell counts and adjust dose as appropriate.

Peripheral Neuropathy: Monitor for signs of neuropathy. Manage with dose delay and adjustment.

Use in Pregnancy: Fetal harm can occur when administered to a pregnant woman.

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Avoid in patients with congenital long QT syndrome.

Interaction

Effects of Other Drugs on Halaven (Intravenous) Mesylate: No drug-drug interactions are expected with CYP3A4 inhibitors or P-gp inhibitors. The effect of ketoconazole, a strong inhibitor of cytochrome P450 3A4 (CYP3A4) and a P-gp inhibitor, on the pharmacokinetics (PK) of eribulin was studied in an open-label, two-treatment, two-sequence, two-way crossover trial in 12 patients with advanced solid tumors. The mean dose-normalized AUC values were similar when eribulin was administered with or without ketoconazole (ratio of the mean AUC: 0.97; 90% CI: 0.83, 1.12).

Effect of Halaven (Intravenous) Mesylate on Other Drugs: Halaven (Intravenous) does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 enzymes or induce CYP1A2, CYP2C9, CYP2C19 or CYP3A4 enzymes at relevant clinical concentrations. Halaven (Intravenous) is not expected to alter the plasma concentrations of drugs that are substrates of these enzymes

Food Interaction

Halaven (Intravenous) Drug Interaction

Moderate: paclitaxel protein-bound, doxorubicin, prochlorperazine, tramadolUnknown: everolimus, ubiquinone, warfarin, medroxyprogesterone, ethanol, levothyroxine, fulvestrant, emollients topical, palbociclib, bioflavonoids, levothyroxine, multivitamin, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

Halaven (Intravenous) Disease Interaction

Major: infectionsModerate: cytopenias, hepatic impairment, peripheral neuropathy, QT prolongation, renal impairment

Volume of Distribution

43 L/m2 to 114 L/m2

Half Life

about 40 hours

Clearance

1.16 L/hr/m2 to 2.42 L/hr/m2 (dose range of 0.25 mg/m2 to 4.0 mg/m2). [FDA]

Elimination Route

Halaven (Intravenous) is eliminated primarily in feces unchanged.

Pregnancy & Breastfeeding use

Pregnancy Category D. There are no adequate and well-controlled studies with Halaven (Intravenous) Mesylate in pregnant women. It is not known whether Halaven (Intravenous) Mesylate is excreted into human milk. No studies in humans or animals were conducted to determine if Halaven (Intravenous) Mesylate is excreted into milk. Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in human milk-fed infants from Halaven (Intravenous) Mesylate, a decision should be made whether to discontinue nursing or to discontinue Halaven (Intravenous) Mesylate taking into account the importance of the drug to the mother.

Acute Overdose

Overdosage of Halaven (Intravenous) has been reported at approximately 4 times the recommended dose, which resulted in Grade 3 neutropenia lasting seven days and a Grade 3 hypersensitivity reaction lasting one day. There is no known antidote for Halaven (Intravenous) overdose.

Storage Condition

Store at 25°C; excursions permitted to 15°-30°C. Do not freeze. Store the vials in their original cartons.

Innovators Monograph

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