Halaven IV Infusion

Halaven is indicated 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.

Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates. Eribulin 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.

The recommended dose of Eribulin 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 Eribulin 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 Eribulin 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 Eribulin 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.

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

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

Pregnancy Category D. There are no adequate and well-controlled studies with Eribulin Mesylate in pregnant women. It is not known whether Eribulin Mesylate is excreted into human milk. No studies in humans or animals were conducted to determine if Eribulin 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 Eribulin Mesylate, a decision should be made whether to discontinue nursing or to discontinue Eribulin Mesylate taking into account the importance of the drug to the mother.

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.

Pediatric Use: The safety and effectiveness of Halaven 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 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.

Overdosage of Halaven 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 overdose.

Targeted Cancer Therapy

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