Approved October 27, 2009

OFATUMUMAB
(FDA Category 1)

ARZERRA(TM) (GlaxoSmithKline) is a CD20-directed human IgG1-kappa monoclonal antibody

DOSING INFORMATION: The recommended dose consists of a 12 dose schedule as follows: initial dose of 300 mg followed 1 week later by 2000 mg weekly for 7 doses, followed 4 weeks later by 2000 mg every 4 weeks for 4 doses.

PHARMACOKINETICS: Following intravenous infusions, the Cmax and AUC were 40% and 60% higher after the 8th infusion than the 4th infusion. The mean Vd at steady state was 1.7 L to 5.1 L, and clearance was dose-dependent over the range of 100 mg to 2000 mg. Clearance decreases substantially after subsequent infusions due to the depletion of B cells and exhibits significant inter-subject variability, with a mean clearance between the 4th and 12th infusions of 0.01 L/hr. The mean half-life between the 4th and 12 infusions was approximately 14 days (range 2.3 to 61.5 days).

CAUTIONS: Premedication is required to prevent infusion reactions. Monitor patient for neutropenia and thrombocytopenia, and neurologic function for evidence of progressive multifocal leukoencephalopathy (PML). Hepatitis B reactivation may occur. Obstruction of the small intestine can occur. The most common adverse reactions include neutropenia, anemia, pneumonia, pyrexia, cough, diarrhea, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections.

FDA APPROVED INDICATIONS: Ofatumumab is indicated for the treatment of chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab.