Animal Data
In an embryo-fetal developmental toxicity study, pregnant rats received intravenous infusion of eribulin mesylate during organogenesis (Gestation Days 8, 10, and 12) at doses approximately 0.04, 0.13, 0.43 and 0.64 times the recommended human dose, based on body surface area. Increased abortion and severe fetal external or soft tissue malformations, including the absence of a lower jaw and tongue, or stomach and spleen, were observed at doses 0.64 times the recommended human dose of 1.4 mg/m2 based on body surface area. Increased embryo-fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay were also reported at doses at or above a maternally toxic dose of approximately 0.43 times the recommended human dose.
8.2 Lactation Risk Summary
There is no information regarding the presence of eribulin mesylate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. No lactation studies in animals were conducted. Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.
8.3 Females and Males of Reproductive Potential Contraception
Females
Based on findings from an animal reproduction study and its mechanism of action, HALAVEN can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose.
Males
Based on its mechanism of action, 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.
Infertility
Males
Based on animal data, HALAVEN may result in damage to male reproductive tissues leading to impaired fertility of unknown duration [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use The safety and effectiveness of HALAVEN in pediatric patients below the age of 18 years have not been established.
8.5 Geriatric Use Study 1 did not include sufficient numbers of subjects with metastatic breast cancer 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 with advanced breast cancer, 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.
Clinical studies of HALAVEN did not include a sufficient number of subjects in Study 2 aged 65 years and older to determine whether they respond differently from younger subjects.
8.6 Hepatic Impairment Administration of HALAVEN at a dose of 1.1 mg/m2 to patients with mild hepatic impairment and 0.7 mg/m2 to patients with moderate hepatic impairment resulted in similar exposure to eribulin as a dose of 1.4 mg/m2 to patients with normal hepatic function. Therefore, a lower starting dose of 1.1 mg/m2 is recommended for patients with mild hepatic impairment (Child-Pugh A) and of 0.7 mg/m2 is recommended for patients with moderate hepatic impairment (Child-Pugh B). HALAVEN was not studied in patients with severe hepatic impairment (Child-Pugh C) [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)]. |
