HALAVEN Clinical Pharmacology Card
HALAVEN™ (eribulin mesylate) Injection
Mechanism of Action | 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. |
Pharmacodynamics (PD) | Effect of HALAVEN on the QTc interval was assessed in patients with solid tumors received 1.4 mg/m2 of HALAVEN on Days 1 and 8 of a 21-day cycle. A delayed QTc prolongation was observed on Day 8, with no prolongation observed on Day 1. The maximum mean QTcF change from baseline (95% upper confidence interval) was 11.4 (19.5) ms. |
Pharmacokinetics (PK) | Linear PK with a mean elimination half-life of approximately 40 hours, a mean volume of distribution of 43 L/m2 to 114 L/m2 and mean clearance of 1.16 L/hr/m2 to 2.42 L/hr/m2 over the dose range of 0.25 mg/m2 to 4.0 mg/m2
Eribulin eliminates primarily in feces as unchanged drug Human plasma protein binding ranged from 49% to 65% No accumulation observed with weekly administration |
PK-PD Analysis | Not evaluated |
Population PK | Gender, race, and age do not have a clinically meaningful effect on the PK of eribulin |
Special Populations | Lower starting dose of 1.1 mg/m2 is recommended for patients with moderate renal impairment |
Drug Interactions | No drug-drug interactions are expected with CYP system or P-gp |
Source : http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf