Pralatrexate

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.

• 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 [ see Clinical Studies (14) ] .ICD-10: C85.90

• None None.( 4 )contraindicated

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. ( 2.1 ) 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. ( 2.1 ) 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 ( 2.1 ). 2.1 Important Dosing Information Pretreatment Vitamin Supplementation Folic Acid Instruct patients to take folic acid 1 to 1.25 mg orally once daily beginning 10 days before the first dose of FOLOTYN. Continue folic acid during treatment with FOLOTYN and for 30 days after the last dose [ see Warnings and Precautions ( 5.1 , 5.2 )] . Vitamin B 12 Administer vitamin B 12 1 mg intramuscularly within 10 weeks prior to the first dose of FOLOTYN and every 8-10 weeks thereafter. Subsequent vitamin B 12 injections may be given the same day as treatment with FOLOTYN [ see Warnings and Precautions ( 5.1 , 5.2 )] . 2.2 Recommended Dosage The recommended dosage of FOLOTYN is 30 mg/m 2 intravenously over 3-5 minutes once weekly for 6 weeks in 7-week cycles until progressive disease or unacceptable toxicity. 2.3 Dosage Modifications for Renal Impairment and End Stage Renal Disease Severe renal impairment (eGFR 15 to 29 mL/min/1.73 m 2 by MDRD): Reduce the FOLOTYN dose to 15 mg/m 2 [ see Use in Specific Populations (8.6) ] .

Myelosuppression : Monitor complete blood counts and omit and/or reduce dose based on ANC and platelet count. ( 2.4 , 5.1 ) Mucositis : Monitor at least weekly. Omit and/or reduce dose for grade 2 or higher mucositis. ( 2.4 , 5.2 ) 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. ( 2.4 , 5.3 ) Tumor lysis syndrome : Monitor patients who are increased risk and treat promptly. ( 5.4 ) Hepatic toxicity : Monitor for liver function tests. Omit until recovery, adjust or discontinue therapy based on severity. ( 2.4 , 5.5 ) Risk of increased toxicity with renal impairment : Avoid FOLOTYN in patients with end stage renal disease with or without dialysis. If the potential benefit of administration justifies the potential risk, monitor renal function and reduce the FOLOTYN dose based on adverse reactions. ( 2.3 , 2.4 , 5.6 ) Embryo-fetal toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use an effective method of contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Myelosuppression FOLOTYN can cause myelosuppression, manifested by thrombocytopenia, neutropenia, and/or anemia. Administer vitamin B 12 and instruct patients to take folic acid to reduce the risk of treatment-related myelosuppression [ see Dosage and Administration (2.1) ] . Monitor complete blood counts and omit and/or reduce the dose based on ANC and platelet count prior to each dose [ see Dosage and Administration (2.4) ] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [ see Warnings and Precautions (5.1) ] Mucositis [ see Warnings and Precautions (5.2) ] Dermatologic Reactions [ see Warnings and Precautions (5.3) ] Tumor Lysis Syndrome [ see Warnings and Precautions (5.4) ] Hepatic Toxicity [ see Warnings and Precautions (5.5) ] Most common adverse reactions (>35%) are mucositis, thrombocytopenia, nausea, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc at 1-888-255-6788 or www.FOLOTYN.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Peripheral T-cell Lymphoma The safety of FOLOTYN was evaluated in Study PDX-008 [ see Clinical Studies (14) ] . Patients received FOLOTYN 30 mg/m 2 once weekly for 6 weeks in 7-week cycles. The median duration of treatment was 70 days (range: 1 day to 1.5 years). The majority of patients (69%, n = 77) remained at the target dose for the duration of treatment. Overall, 85% of scheduled doses were administered. Forty-four percent of patients (n = 49) experienced a serious adverse event while on study or within 30 days after their last dose of FOLOTYN.

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [ see Clinical Pharmacology (12.1) ] , FOLOTYN can cause fetal harm when administered to a pregnant woman. There are insufficient data on FOLOTYN use in pregnant women to evaluate for a drug- associated risk. FOLOTYN was embryotoxic and fetotoxic in rats and rabbits when administered during organogenesis at doses about 1.2% (0.012 times) of the clinical dose on a mg/m 2 basis. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Pralatrexate was embryotoxic and fetotoxic in rats at intravenous doses of 0.06 mg/kg/day (0.36 mg/m 2 /day or about 1.2% of the clinical dose on a mg/m 2 basis) given on gestation days 7 through 20. Treatment with pralatrexate caused a dose-dependent decrease in fetal viability manifested as an increase in late, early, and total resorptions. There was also a dose-dependent increase in post-implantation loss.

Metabolism

Pralatrexate is a racemic mixture of S- and R-diastereomers. The pharmacokinetics of pralatrexate at the recommended dosage of 30 mg/m 2 once weekly have been evaluated in 10 patients with PTCL.

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 healthcare provider. Based on FOLOTYN's mechanism of action, consider the prompt administration of leucovorin.

• Sep 24, 2009NDANDA022468Acrotech Biopharma
• Mar 10, 2025ANDAANDA206183Dr Reddys

1. 1Malignant Neoplasm Progression11818%
2. 2Stomatitis10316%
3. 3Disease Progression6911%
4. 4Mucosal Inflammation639.8%
5. 5Platelet Count Decreased578.9%
6. 6Pyrexia487.5%
7. 7Anaemia457.0%
8. 8Neutrophil Count Decreased416.4%
9. 9Drug Ineffective406.2%
10. 10Febrile Neutropenia385.9%
11. 11Death325.0%
12. 12Off Label Use325.0%
13. 13Thrombocytopenia325.0%
14. 14Neutropenia314.8%
15. 15Nausea253.9%

The 10 most recently updated of 43 ClinicalTrials.gov registrations naming Pralatrexate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pembrolizumab and Pralatrexate in Treating Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 13 enrolled · City of Hope Medical Center
  NCT03598998updated 2026-05-26
• Pralatrexate With Bendamustine and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 50 enrolled · Fred Hutchinson Cancer Center
  NCT07225985updated 2026-05-11
• Soquelitinib vs Standard of Care in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma Not Otherwise Specified, Follicular Helper T-cell Lymphomas, or Systemic Anaplastic Large-cell Lymphoma
  Recruiting · Phase 3 · Interventional · 150 enrolled · Corvus Pharmaceuticals, Inc.
  NCT06561048updated 2026-04-08
• Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL
  Active not recruiting · Phase 1 · Interventional · 37 enrolled · University of Virginia
  NCT03240211updated 2026-04-07
• Study to Evaluate the Pharmacokinetics and Safety of Pralatrexate in Patients With Advanced Solid Tumor or Hematological Malignancy and Either Normal Hepatic Function or Mild, Moderate, or Severe Hepatic Impairment
  Recruiting · Phase 1 · Interventional · 24 enrolled · Acrotech Biopharma Inc.
  NCT07036133updated 2026-02-11
• Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator's Choice in PTCL
  Recruiting · Phase 2 · Interventional · 50 enrolled · University of Virginia
  NCT04747236updated 2026-01-21
• To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
  Recruiting · Phase 3 · Interventional · 504 enrolled · Acrotech Biopharma Inc.
  NCT06072131updated 2025-10-23
• Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma
  Recruiting · Early phase 1 · Interventional · 40 enrolled · New York Medical College
  NCT03719105updated 2025-08-08
• Pralatrexate Combined With Chidamide Bridging Allogeneic HSCT for Refractory/Relapsed Peripheral T-cell Lymphoma
  Not yet recruiting · Interventional · 25 enrolled · Peking University People's Hospital
  NCT06671717updated 2024-11-06
• KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
  Completed · Phase 2 · Interventional · 71 enrolled · Kyowa Kirin, Inc.
  NCT01626664updated 2024-04-25

Frequently asked questions

How does Pralatrexate work?

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.

What is Pralatrexate used for?

According to FDA labeling, Pralatrexate carries indications including: 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 [ see Clinical Studies (14) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pralatrexate?

Pralatrexate is classified as Folic acid analogues, Folate Analog Metabolic Inhibitor, Dihydrofolate Reductase Inhibitors, Protein Synthesis Inhibitors, Decreased Protein Synthesis.

What are the brand names for Pralatrexate?

Pralatrexate is marketed under brand names including Folotyn.

What are the contraindications for Pralatrexate?

Pralatrexate labeling lists contraindications including: None None.( 4 ). Always consult the full prescribing information and a clinician.