Approved September 24, 2009

PRALATREXATE
(FDA Category 1P)

FOLOTYN(TM) (Allos Therapeutics, Inc) is a folate analogue that competitively inhibits dihydrofolate reductase. It also causes the depletion of thymidine and other biological molecules by competitively inhibiting polyglutamylation by the enzyme folylpolyglutamyl.

DOSING INFORMATION: The recommended dosage is 30 milligrams/square meter (mg/m(2)) given as an intravenous (IV) push over 3 to 5 min once weekly for 6 weeks of a 7-week cycle. Doses may be omitted or reduced based on patient tolerance. All patients should receive vitamin B12 1 mg intramuscularly every 8 to 10 weeks and folic acid 1 to 1.25 mg orally once daily.

PHARMACOKINETICS: The total systemic clearance of pralatrexate was 417 milliliters/minute (mL/min) (S-diastereomer) and 191 mL/min (R-diastereomer) and the terminal elimination half-life was 12 to 18 hours in 10 healthy volunteers. Pralatrexate has a steady-state volume of distribution of 105 liters (L) (S-diastereomer) and 37 L (R-diastereomer) and is about 67% protein bound. The mean fraction of unchanged diastereomers excreted in the urine after a 30 mg/m(2) IV dose was 31% (S-diastereomer) and 38% (R-diastereomer).

CAUTIONS: Use with caution in patients with moderate to severe renal impairment. Serious toxicities include pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, thrombocytopenia. The most common adverse reactions include mucositis, thrombocytopenia, nausea, and fatigue.

FDA APPROVED INDICATIONS: Pralatrexate is indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma.