Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Chemically it is a synthetic antifolate analogue designed for high affinity uptake by the reduced folate carrier SLC19A1 and for efficient intracellular polyglutamation by folylpolyglutamate synthase, which increases cellular retention and potency. The intracellular polyglutamates disrupt folate-dependent one carbon metabolism, leading to inhibition of dihydrofolate reductase and downstream thymidylate and purine biosynthesis, producing S-phase cytotoxicity and apoptosis in susceptible lymphoid cells. The product is formulated for intravenous administration; the labeled dosing regimen is 30 mg per square meter given once weekly for six weeks followed by one week off in a seven week cycle, with recommended folic acid and vitamin B12 supplementation to reduce mucosal and hematologic toxicity. Major safety considerations include mucositis, thrombocytopenia, neutropenia, and infectious risk, and handling requires standard cytotoxic precautions and refrigerated storage.
Parent: Pralatrexate
Parent: Pralatrexate
Parent: Pralatrexate
Pralatrexate drug substance and finished product are controlled to a defined related-substance and impurity profile consistent with ICH guidelines; specified degradation products and process-related impurities are typically limited to not more than 0.10 percent each by weight and total specified and unspecified impurities are limited to not more than 0.30 percent by weight unless otherwise justified and qualified. Typical related compounds monitored in stability and release testing include N-oxide derivatives, O- or N-dealkylated species, deamidation and hydrolysis products, positional isomers and trace synthetic byproducts; each of these is usually controlled at the individual 0.10 percent limit. Residual solvents and catalysts are controlled to ICH Q3C and Q3D acceptable limits and elemental impurities are controlled per risk assessment with limits in accordance with the applicable pharmacopeial monographs.
Pralatrexate is indicated for treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma and is used as an intravenous antineoplastic agent in that setting.
Pralatrexate is an antifolate that is preferentially transported into cells via the reduced folate carrier and polyglutamated intracellularly; its polyglutamated forms inhibit folate-dependent enzymes including dihydrofolate reductase, impairing thymidylate and purine synthesis and causing cytotoxicity in proliferating malignant lymphocytes.
Cost varies by country, supplier, dosing regimen and payer coverage; in practice the per-vial price in the United States has been reported in the low thousands of dollars range for a 10 mg vial and a full course of therapy can run into tens of thousands of dollars; patients should consult their specialty pharmacy, insurer or manufacturer assistance programs for current pricing and available financial support.
Yes, pralatrexate is approved by the United States Food and Drug Administration for the treatment of relapsed or refractory peripheral T-cell lymphoma.
