Approved March 20, 2008

BENDAMUSTINE HYDROCHLORIDE
(FDA Category 1P, O)

TREANDA (Cephalon, Inc) is an alkylating agent which is a bifunctional mechlorethamine derivative. The clinical efficacy is related to the formation of covalent bonds with electronrich nucleophilic moieties which result in cell death.

DOSING INFORMATION: The recommended dose of bendamustine hydrochloride is 100 milligrams/square meter (mg/m(2)) intravenously over 30 minutes on day 1 and 2 of a 28-day cycle, up to a maximum of 6 cycles.

PHARMACOKINETICS: The plasma protein binding of bendamustine hydrochloride (HCl) is high (94-96%), although it is not likely to displace or be displaced by other highly protein-bound drugs. The mean steady-state volume of distribution for bendamustine HCl is 25 L/hr and clearance is 700 mL/min. It is primarily metabolized via hydrolysis but also undergoes oxidative metabolism via CYP1A2 to form 2 minor, minimally active metabolites. About 90% of bendamustine HCl is excreted in the feces. The intermediate half-life of bendamustine HCl was approximately 40 min following a single dose of 120 mg/m2 and very little or no accumulation in plasma is expected following each cycle.

CAUTIONS: Severe anaphylactic reactions, skin toxicities, and infection have been reported. The most common side effects are myelosuppression (neutropenia, thrombocytopenia, anemia, leukopenia), pyrexia, nausea, and vomiting. Take precautions (eg, administer allopurinol) in patients at high risk for tumor lysis syndrome.

FDA APPROVED INDICATIONS: Bendamustine hydrochloride is indicated for the treatment of chronic lymphocytic leukemia.