halaven

Important safety information

Neutropenia: Monitor peripheral blood cell counts and adjust dose as appropriate. ( 5.1 ) Peripheral Neuropathy: Monitor for signs of neuropathy. Manage with dose delay and adjustment. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 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. ( 5.4 ) 5.1 Neutropenia In Study 1, severe neutropenia (ANC < 500/mm3) lasting more than one week occurred in 12% (62/503) of patients with metastatic breast cancer, leading to discontinuation in <1% of patients. Febrile neutropenia (fever ≥38.5°C with Grade 3 or 4 neutropenia) occurred in 5% (23/503) of patients; two patients (0.4%) died from complications of febrile neutropenia [see Adverse Reactions (6.1) ]. In Study 1, patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × ULN (upper limit of normal) experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal aminotransferase levels. Patients with bilirubin > 1.5 × ULN also had a higher incidence of Grade 4 neutropenia and febrile neutropenia. In Study 2, severe neutropenia (ANC < 500/mm3) lasting more than one week occurred in 12% (26/222) of patients with liposarcoma or leiomyosarcoma. Febrile neutropenia occurred in 0.9% of patients treated with HALAVEN and fatal neutropenic sepsis in 0.9% [see Adverse Reactions (6.1) ]. Monitor complete blood counts prior to each dose; increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration of HALAVEN and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting longer than 7 days [ see Dosage and Administration (2.2) ] . Clinical studies of HALAVEN did not include patients with baseline neutrophil counts below 1,500/mm 3 . 5.2 Peripheral Neuropathy In Study 1, Grade 3 peripheral neuropathy occurred in 8% (40/503) of patients, and Grade 4 in 0.4% (2/503) of patients with metastatic breast cancer (MBC). Peripheral neuropathy was the most common toxicity leading to discontinuation of HALAVEN (5% of patients; 24/503) in Study 1. Neuropathy lasting more than one year occurred in 5% (26/503) of patients. Twenty-two percent (109/503) of patients developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). In Study 2, Grade 3 peripheral neuropathy occurred in 3.1% (7/223) of HALAVEN-treated patients. Peripheral neuropathy led to discontinuation of HALAVEN in 0.9% of patients. The median time to first occurrence of peripheral neuropathy of any severity was 5 months (range: 3.5 months to 9 months). Neuropathy lasting more than 60 days occurred in 58% (38/65) of patients. Sixty three percent (41/65) had not recovered within a median follow-up duration of 6.4 months (range: 27 days to 29 months). Monitor patients closely for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy, until resolution to Grade 2 or less [ see Dosage and Administration (2.2) ] . 5.3 Embryo - Fetal Toxicity Based on findings from an animal reproduction study and its mechanism of action, HALAVEN can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of HALAVEN in pregnant women. In animal reproduction studies, eribulin mesylate caused embryo-fetal toxicity when administered to pregnant rats during organogenesis at doses below the recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose [see Use in Specific Populations (8.1) ] . 5.4 QT Prolongation In an uncontrolled open-label ECG study in 26 patients, QT prolongation was observed on Day 8, independent of eribulin concentration, with no QT prolongation observed on Day 1. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy. Avoid HALAVEN in patients with congenital long QT syndrome.