ed hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Since elderly patients may be at higher risk, monitor more closely. Omit dose and subsequently adjust or discontinue therapy for exposure related toxicity [see Dosage and Administration (2.2), Warnings and Precautions (5.5)(5.6), Use in Specific Populations (8.6)(8.7), and Clinical Pharmacology (12.3)].
Hepatic Impairment
The safety, efficacy and pharmacokinetics of Folotyn have not been eva luated in patients with hepatic impairment. Patients with the following laboratory values were excluded from the pralatrexate lymphoma clinical trials: total bilirubin > 1.5 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN); and AST or ALT > 5 × ULN if documented hepatic involvement with lymphoma. Treatment with Folotyn can cause hepatic toxicity and liver function test abnormalities [see Dosage and Administration (2.2) and Warnings and Precautions (5.6)].
Renal Impairment
The safety, efficacy and pharmacokinetics of Folotyn have not been eva luated in patients with renal impairment.
The risk for toxicity may be greater when administering Folotyn to patients with moderate-to-severe impairment due to the contribution of renal excretion (approximately 34%) to the overall clearance of pralatrexate. Serious adverse drug reactions, including TEN and mucositis have been reported in patients with ESRD undergoing dialysis. Monitor patients for renal function and for systemic toxicity due to increased drug exposure and adjust dosing accordingly. Avoid the use of Folotyn in patients with end stage renal disease undergoing dialysis unless the potential benefit justifies the potential risk [see Dosage and Administration (2.2), Warnings and Precautions (5.3)(5.6), Adverse Reactions (6.2), and Clinical Pharmacology (12.3)].
Overdosage
No specific information is available on the treatment of overdosage of Folotyn. If an overdose occurs, general supportive measures should be instituted as deemed necessary by the treating physician. Based on Folotyn's mechanism of action, consider the prompt administration of leucovorin.
Folotyn Description
Folotyn (pralatrexate injection) contains pralatrexate, which is an antineoplastic folate analog. Pralatrexate has the chemical name (2S)-2-[[4-[(1RS)-1-[(2, 4-diaminopteridin-6-yl)methyl]but-3-ynyl]benzoyl]amino]pentanedioic acid. The structural formula is as follows:
Pralatrexate is a 1:1 racemic mixture of S- and R- diastereomers at the C10 position (indicated with *).
The molecular formula is C23H23N7O5 and the molecular weight is 477.48 g/mol.
Pralatrexate is an off-white to yellow solid. It is soluble in aqueous solutions at pH 6.5 or higher. Pralatrexate is practically insoluble in chloroform and ethanol. The pKa values are 3.25, 4.76, and 6.17.
Folotyn is supplied as a preservative-free, sterile, isotonic, non-pyrogenic clear yellow aqueous parenteral solution contained in a single-use clear glass vial (Type I) for intravenous administration. Each 1 mL of solution contains 20 mg of pralatrexate, sufficient sodium chloride to achieve an isotonic (280-300 mOsm) solution, and sufficient sodium hydroxide, and hydrochloric acid if needed, to adjust and maintain the pH at 7.5-8.5. Folotyn is supplied as either 20 mg (1 mL) or 40 mg (2 mL) single-use vials at a concentration of 20 mg/mL.
Folotyn - Clinical Pharmacolo |
