Products
Pralatrexate is commercially available as an infusion solution (Folotyn). It has been approved in many countries since 2013.
Structure and properties
Pralatrexate (C23H23N7O5, Mr = 477.5 g/mol) is a folic acid analog and exists as a racemate. It is a white to yellow substance that is soluble in water.
Effects
Pralatrexate (ATC L01BA05) has cytotoxic properties and reduces tumor growth. The effects are due to competitive inhibition of dihydrofolate reductase and folylpolyglutamyl synthetase. This results in depletion of thymidine and other molecules responsible for transfer of single carbon molecules. DNA synthesis is interrupted, leading to cell death. Pralatrexate accumulates selectively in tumor cells by being taken up via Reduced Folate Carrier Type 1 (RFC-1). This protein is overexpressed in tumor cells. The mechanism of action is essentially the same as that of methotrexate.
Indications
For the treatment of adults with peripheral T-cell lymphoma whose disease has progressed after at least one prior therapy.
Dosage
According to the SmPC. The drug is administered as an intravenous infusion.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Pralatrexate does not interact with CYP450 isozymes. It is a weak inhibitor of OATP1B1, MRP2, and MRP3. Another interaction has been described with probenecid.
Adverse effects
The most common potential adverse effects include inflammation of the oral mucosa, thrombocytopenia, nausea, anemia, fatigue, neutropenia, nosebleeds, vomiting, and constipation.
