Eribulin

729.89656

729.90

-0

LR24G6354G

C96748

L01XX41|L - Antineoplastic and immunomodulating agents

146

3.88

1.29±0.1 g/cm3

1.584

H2O: Practically insoluble (0.015 g/L) (25 ºC)

P201, P202, P261, P264, P270, P271, P280, P281, P301+P310, P302+P352, P304+P340, P308+P313, P311, P312, P321, P322, P330, P361, P363, P403+P233, P405, P501

H301+H311+H331

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.

Eribulin is a cytotoxic chemotherapeutic agent and serum aminotransferase and alkaline phosphatase elevations are common during cyclic therapy of breast cancer and liposarcoma. The reported rates of ALT elevations have ranged from 8% to 83% with values above 5 times the upper limit or normal (ULN) in 2% to 5%. Isolated mention of “toxic hepatitis” have been made in reports of clinical trials of eribulin but no details of the onset, clinical features and course have been published and the role of eribulin in these outcomes is uncertain. Nevertheless, despite high rates of serum enzyme elevations during treatment, cases of clinically apparent liver injury have not been reported in detail and must be rare.

49 to 65%.

For the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic cancer.|FDA Label|Halaven monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimens for advanced disease (see section 5.1). Prior therapy should have included an anthracycline and a taxane unless patients were not suitable for these treatments.Halaven is indicated for the treatment of adult patients with unresectable liposarcoma who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease (see section 5.1).|Treatment of soft tissue sarcoma|Drug: Eribulinmesylate

Eribulin mesylate is an inhibitor of microtubule function and is used as an antineoplastic agent for refractory, metastatic breast cancer and liposarcoma. Despite its cytotoxic activity against cancer cells, eribulin has rarely been implicated in causing clinically apparent acute liver injury.

Antineoplastic Agents

Linear

Eribulin is eliminated primarily in feces unchanged.|43 L/m2 to 114 L/m2|1.16 L/hr/m2 to 2.42 L/hr/m2 (dose range of 0.25 mg/m2 to 4.0 mg/m2). [FDA]

There are no major human metabolites of eribulin, CYP3A4 negligibly metabolizes eribulin in vitro.

about 40 hours

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. [FDA]

B 1793

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