Pralatrexate

FOLOTYN is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). FOLOTYN is a dihydrofolate reductase inhibitor indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules the synthesis of which depends on single carbon transfer.

Supplement patients with vitamin B 12 mg intramuscularly every 8-10 weeks starting 10 weeks before the first dose and folic acid 1 to 1.25 mg orally once daily starting 10 days before the first dose. The recommended dosage of FOLOTYN is 30 mg/m 2 intravenously over 3 to 5 minutes once weekly for 6 weeks in 7-week cycles. For patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m 2 ), reduce the FOLOTYN dose to 15 mg/m 2.

None None.

Myelosuppression: Monitor complete blood counts and omit and/or reduce dose based on ANC and platelet count. Mucositis: Monitor at least weekly. Omit and/or reduce dose for grade 2 or higher mucositis. Dermatologic reactions: Reactions, including fatal reactions, occurred and may be progressive and increase in severity with further treatment. Monitor closely and withhold or discontinue FOLOTYN based on severity. Tumor lysis syndrome: Monitor patients who are increased risk and treat promptly. Hepatic toxicity: Monitor for liver function tests. Omit until recovery, adjust or discontinue therapy based on severity. Risk of increased toxicity with renal impairment: Avoid FOLOTYN in patients with end stage renal disease with or without dialysis.

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression Mucositis Dermatologic Reactions Tumor Lysis Syndrome Hepatic Toxicity Most common adverse reactions (>35%) are mucositis, thrombocytopenia, nausea, and fatigue.

Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions.

Store refrigerated at 2-8°C (36-46°F) in original carton to protect from light.