Folotyn pralatrexate 20 mg/mL Injection, 1 vial
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Folate Analog Metabolic Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Pralatrexate injection is a chemotherapy used specifically for peripheral T-cell lymphoma — a type of blood cancer affecting T-cells — when it has come back after treatment or stop...
- These supplements are really important — they help protect your body from some of pralatrexate's most serious side effects, especially mouth sores and low blood counts. You need to...
- Why do I have to take folic acid and vitamin B12 before my infusions?
- The ones to act on immediately are: severe or worsening mouth sores that make it hard to eat or drink, signs of infection like fever or chills (which can signal dangerously low whi...
Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $712.16 | $712.16 / 1 vial |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9307 | $386.122 / J9307 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pralatrexate 20 mg/mL 43598-0342-11 | Dr.Reddy's | 1 vial | — | AP | FDA listed | — |
| Pralatrexate 20 mg/mL 65219-0550-01 | Fresenius | 1 vial | — | AP | FDA listed | — |
| Folotyn 20 mg/mLthis 72893-0003-01 | Acrotech | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72893-0003-01 You're viewing this | 1 VIAL in 1 CARTON (72893-003-01) / 1 mL in 1 VIAL | 2009-09-24 | Active |
🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE 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) ] . 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). 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).
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 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 ).
2.1Important 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 )] .
2.2Recommended 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.
2.3Dosage 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) ] . End stage renal disease (ESRD: eGFR less than 15 mL/min/1.73 m 2 by MDRD) with or without dialysis: Avoid administration. If the potential benefit of administration justifies the potential risk, monitor renal function and reduce the FOLOTYN dose based on adverse reactions [ see Warnings and Precautions (5.6) , Use in Specific Populations (8.6) ] .
2.4Monitoring and Dosage Modifications for Adverse Reactions Monitoring Monitor complete blood cell counts and severity of mucositis at baseline and weekly. Perform serum chemistry tests, including renal and hepatic function, prior to the start of the first and fourth dose of each cycle. Recommended Dosage Modifications Do not administer FOLOTYN until: Mucositis Grade 1 or less.
Platelet of 100,000/mcL or greater for first dose and 50,000/mcL or greater for all subsequent doses. Absolute neutrophil count (ANC) of 1,000/mcL or greater. Dosage modifications for adverse reactions are provided in Tables 1, 2, and 3.
Table 1 FOLOTYN Dose Modifications for Mucositis Mucositis Grade a on Day of Treatment Action Recommended Dose upon Recovery to Grade 0 or 1 Patients Without Severe Renal Impairment Patients with Severe Renal Impairment Grade 2 Omit dose Continue prior dose Continue prior dose Grade 2 recurrence Omit dose 20 mg/m 2 10 mg/m 2 Grade 3 Omit dose 20 mg/m 2 10 mg/m 2 Grade 4 Stop therapy a Based National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 3.0) Table 2 FOLOTYN Dosage Modifications for Myelosuppression Blood Count on Day of Treatment Duration of Toxicity Action Recommended Dose Upon Recovery Patients Without Severe Renal Impairment Patients with Severe Renal Impairment Platelet less than 50,000/mcL 1 week Omit dose Continue prior dose Continue prior dose 2 weeks Omit dose 20 mg/m 2 10 mg/m 2 3 weeks Stop therapy ANC 500 to 1,000/mcL and no fever 1 week Omit dose Continue prior dose Continue prior dose ANC 500 to 1,000/mcL with fever or ANC less than 500/mcL 1 week Omit dose, give G‑CSF or GM‑CSF Continue prior dose with G-CSF or GM‑CSF Continue prior dose with G-CSF or GM‑CSF support 2 weeks or recurrence Omit dose, give G‑CSF or GM‑CSF 20 mg/m 2 with G-CSF or GM-CSF 10 mg/m 2 with G-CSF or GM-CSF 3 weeks or 2 nd recurrence Stop therapy G-CSF=granulocyte colony-stimulating factor; GM-CSF=granulocyte macrophage colony-stimulating factor Table 3 FOLOTYN Dosage Modifications for All Other Adverse Reactions Toxicity Grade a on Day of Treatment Action Rec…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: 40 mg/2 mL (20 mg/mL) and 20 mg/mL clear yellow sterile solution in single-dose vial Injection: 20 mg/1 mL or 40 mg/2 mL in a single-dose vial ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None None.( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 )
5.1Myelosuppression 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) ] .
5.2Mucositis FOLOTYN can cause mucositis [ see Adverse Reactions (6.1) ] . Administer vitamin B 12 and instruct patients to take folic acid to reduce the risk of mucositis [ see Dosage and Administration (2.1) ] . Monitor for mucositis weekly and omit and/or reduce the dose for grade 2 or higher mucositis [ see Dosage and Administration (2.4) ] .
5.3Dermatologic Reactions FOLOTYN can cause severe dermatologic reactions, which may result in death. These dermatologic reactions have been reported in clinical studies (2.1% of 663 patients) and post marketing experience, and have included skin exfoliation, ulceration, and toxic epidermal necrolysis (TEN) [ see Adverse Reactions (6.1 , 6.2) ] . They may be progressive and increase in severity with further treatment and may involve skin and subcutaneous sites of known lymphoma.
Monitor closely for dermatologic reactions. Withhold or discontinue FOLOTYN based on severity [ see Dosage and Administration (2.4) ] .
5.4Tumor Lysis Syndrome FOLOTYN can cause tumor lysis syndrome (TLS). Monitor patients who are at increased risk of TLS and treat promptly.
5.5Hepatic Toxicity FOLOTYN can cause hepatic toxicity and liver function test abnormalities [ see Adverse Reactions (6.1) ] . Persistent liver function test abnormalities may be indicators of hepatic toxicity and require dose modification or discontinuation. Monitor liver function tests. Omit dose until recovery, adjust or discontinue therapy based on the severity of the hepatic toxicity [ see Dosage and Administration (2.4) ] .
5.6Risk of Increased Toxicity with Renal Impairment Patients with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m 2 based on MDRD) may be at greater risk for increased exposure and adverse reactions. Reduce FOLOTYN dosage in patients with severe renal impairment [ see Dosage and Administration (2.3) ] . Serious adverse reactions, including TEN and mucositis, were reported in patients with end stage renal disease (ESRD) undergoing dialysis who were administered FOLOTYN.
Avoid FOLOTYN in patients with ESRD 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 [ see Dosage and Administration (2.3) ] .
5.7Embryo-Fetal Toxicity Based on findings in animals and its mechanism of action, FOLOTYN can…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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
6.1Clinical 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. The most common serious adverse events (> 3%), regardless of causality, were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. One death from cardiopulmonary arrest in a patient with mucositis and febrile neutropenia was reported in this trial.
Across clinical trials, deaths from mucositis, febrile neutropenia, sepsis, and pancytopenia occurred in 1.2% of patients who received doses ranging from 30 mg/m 2 to 325 mg/m 2 . Twenty-three percent of patients (n = 25) discontinued treatment with FOLOTYN due to adverse reactions. The most frequent adverse reactions reported as the reason for discontinuation of treatment were mucositis (6%) and thrombocytopenia (5%).
The most common adverse reactions (> 35%) were mucositis, thrombocytopenia, nausea, and fatigue. Table 4 summarizes the adverse reactions in Study PDX-008. Table 4 Adverse Reactions in (≥ 10%) in Patients Who Received FOLOTYN in Study PDX-008 FOLOTYN N=111 All Grades (%) Grade 3 (%) Grade 4 (%) Any Adverse Event 100 43 31 Mucositis a 70 17 4 Thrombocytopenia b 41 14 19 b Nausea 40 4 0 Fatigue 36 5 2 Anemia 34 15 2 Constipation 33 0 0 Pyrexia 32 1 1 Edema 30 1 0 Cough 28 1 0 Epistaxis 26 0 0 Vomiting 25 2 0 Neutropenia 24 13 7 Diarrhea 21 2 0 Dyspnea 19 7 0 Hypokalemia 15 4 1 Anorexia 15 3 0 Rash 15 0 0 Pruritus 14 2 0 Pharyngolaryngeal pain 14 1 0 Liver function test abnormal c 13 5 0 Abdominal pain 12 4 0 Pain in extremity 12 0 0 Leukopenia 11 3 4 Back pain 11 3 0 Night sweats 11 0 0 Asthenia 10 1 0 Upper respiratory tract infection 10 1 0 Tachycardia 10 0 0 a Mucositis includes stomatitis or mucosal inflammation of the gastrointestinal and genitourinary tracts. b Five patients with platelets < 10,000/mcL c Liver function test abnormal includes increased ALT, increased AST, and increased transaminases
6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of FOLOTYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Dermatologic Reactions : Toxic epidermal necrolysis.
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions. ( 7.1 )
7.1Effects of Other Drugs on FOLOTYN Coadministration of FOLOTYN with probenecid increased pralatrexate plasma concentrations [ see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions. Avoid coadministration with probenecid or nonsteroidal anti-inflammatory drugs. If coadministration is unavoidable, monitor for increased risk of adverse reactions.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 )
8.1Pregnancy 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. In rabbits, intravenous doses of 0.03 mg/kg/day (0.36 mg/m 2 /day) or greater given on gestation days 8 through 21 also caused abortion and fetal lethality. This toxicity manifested as early and total resorptions, post-implantation loss, and a decrease in the total number of live fetuses.
8.2Lactation Risk Summary There is no data on the presence of pralatrexate in human milk or its effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with FOLOTYN and for 1 week after the last dose.
8.3Females and Males of Reproductive Potential FOLOTYN can cause fetal harm when administered to a pregnant woman [ see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiation of FOLOTYN. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with FOLOTYN and for 6 months following the last dose.
Males Advise males with female partners of reproductive potential to use effective contraception during treatment with FOLOTYN and for 3 months following the last dose.
8.4Pediatric Use The safety and effectiveness of FOLOTYN in pediatric patients have not been established.
8.5Geriatric Use In the Study PDX-008, 36% of patients (n = 40) were 65 years of age and over. No overall differences in efficacy and safety were observed in patients based on age (< 65 years compared with ≥ 65 years). Due to the contribution of renal excretion to overall clearance of pralatrexate (approximately 34%), age-related decline in renal function may lead to a reduction in clearance and a commensurate increase in plasma exposure.
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased 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 adverse reactions [ see Dosage and Administration (2.4) ] .
8.6Renal Impairment No dosage modification is recommended for patients with mild or moderate renal impairment (eGFR 30 to 59 mL/min/1.73 m 2 based on MDRD). For patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m 2 ), reduce the recommended dose of FOLOTYN [ see Dosage and Administration (2.3) ] . Serious adverse drug reactions, including TEN and mucositis, have been reported in patients with ESRD undergoing dia…
🤰 Pregnancy ▾
8.1Pregnancy 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. In rabbits, intravenous doses of 0.03 mg/kg/day (0.36 mg/m 2 /day) or greater given on gestation days 8 through 21 also caused abortion and fetal lethality. This toxicity manifested as early and total resorptions, post-implantation loss, and a decrease in the total number of live fetuses.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of FOLOTYN in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use In the Study PDX-008, 36% of patients (n = 40) were 65 years of age and over. No overall differences in efficacy and safety were observed in patients based on age (< 65 years compared with ≥ 65 years). Due to the contribution of renal excretion to overall clearance of pralatrexate (approximately 34%), age-related decline in renal function may lead to a reduction in clearance and a commensurate increase in plasma exposure.
In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased 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 adverse reactions [ see Dosage and Administration (2.4) ] .
🆘 Overdosage ▾
10 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 healthcare provider. Based on FOLOTYN's mechanism of action, consider the prompt administration of leucovorin.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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.
12.2Pharmacodynamics Pralatrexate exposure-response relationship and the time course of pharmacodynamics responses are unknown.
12.3Pharmacokinetics 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. Pralatrexate total systemic exposure (AUC) and maximum plasma concentration (Cmax) increased proportionally over a dose range 30 to 325 mg/m 2 (10.8 times the approved recommended dosage).
No accumulation of pralatrexate was observed. Distribution Steady-state volume of distribution of pralatrexate S- and R-diastereomers is 105 L and 37 L, respectively. Protein binding of pralatrexate is approximately 67% in vitro.
Elimination The total systemic clearance of pralatrexate diastereomers was 417 mL/min (S-diastereomer) and 191 mL/min (R-diastereomer). The terminal elimination half-life of pralatrexate was 12-18 hours (coefficient of variance [CV] = 62-120%). Metabolism Pralatrexate is not significantly metabolized by CYP450 isozymes or glucuronidases in vitro.
Excretion Following a single dose of FOLOTYN 30 mg/m 2 , approximately 34% of the pralatrexate dose was excreted unchanged into urine. Following a radiolabeled pralatrexate dose, 39% (CV = 28%) of the dose was recovered in urine as unchanged pralatrexate and 34% (CV = 88%) in feces as unchanged pralatrexate and/or any metabolites. 10% (CV = 95%) of the dose was exhaled over 24 hours.
Specific Populations No clinically meaningful effect on the pharmacokinetics of pralatrexate was observed based on sex. The effect of hepatic impairment on the pharmacokinetics of pralatrexate has not been studied. Patients with Renal Impairment Following administration of a single dose of FOLOTYN, mean exposures of the pralatrexate S-diastereomer and R- diastereomer were comparable in patients with mild to moderate (eGFR 30 to 59 mL/min/1.73 m 2 based on MDRD) renal impairment as compared with severe (eGFR 15 to 29 mL/min/1.73 m 2 ) renal impairment.
The mean fraction of the administered dose excreted as unchanged diastereomers in urine (f e ) decreased with declining renal function [ see Use in Specific Populations (8.6) ] . Drug Interaction Studies Clinical Studies Coadministration of probenecid (an inhibitor of multidrug resistance-associated protein 2 [MRP2] in vitro) resulted in delayed clearance of pralatrexate. In Vitro Studies Cytochrome P450 (CYP) Enzymes : Pralatrexate does not induce or inhibit CYP enzymes.
Transporter Systems : Pralatrexate is a substrate for BCRP, MRP2, MRP3, and OATP1B3, but is not a substrate of P-gp, OATP1B1, OCT2, OAT1, or OAT3. Pralatrexate inhibits MRP2 and MRP3, but does not inhibit P-gp, BCRP, OCT2, OAT1, OAT3, OATP1B1, or OATP1B3. MRP3 is a transporter that may affect the transport of etoposide and teniposide.
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING FOLOTYN is available in clear glass single-dose vials containing pralatrexate at a concentration of 20 mg/mL as a preservative-free, sterile, clear yellow solution individually packaged for intravenous use in the following presentations: NDC 72893-003-01 : 20 mg of pralatrexate in 1 mL solution in a vial (20 mg / 1 mL) NDC 72893-005-01 : 40 mg of pralatrexate in 2 mL solution in a vial (40 mg / 2 mL) Store refrigerated at 2-8°C (36-46°F) [see USP Controlled Cold Temperature] in original carton to protect from light.
FOLOTYN is a hazardous drug. Follow applicable special handling and disposal procedures. 1
📋 Description ▾
11 DESCRIPTION Pralatrexate is a dihydrofolate reductase inhibitor. Pralatrexate has the chemical name (2S)-2-[[4-[(1RS)-1-[(2, 4-diaminopteridin-6-yl)methyl]but-3- ynyl]benzoyl]amino]pentanedioic acid. The molecular formula is C 23 H 23 N 7 O 5 and the molecular weight is 477.48 g/mol.
Pralatrexate is a 1:1 racemic mixture of S- and R- diastereomers at the C10 position (indicated with *). The structural formula is as follows: 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 (pralatrexate) is supplied as a preservative-free, sterile, isotonic, non-pyrogenic clear yellow aqueous solution contained in a clear glass single-dose vial (Type I) for intravenous use.
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-dose vials at a concentration of 20 mg/mL. Structural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Folic Acid and Vitamin B 12 Supplementation Advise patients treated with FOLOTYN to take folic acid and vitamin B12 to reduce the risk of possible side effects [ see Dosage and Administration (2.1) ] . Myelosuppression Inform patients of the risk of myelosuppression and to immediately contact their healthcare provider should any signs of infection develop, including fever.
Inform patients to contact their healthcare provider if bleeding or symptoms of anemia occur [ see Warnings and Precautions (5.1) ] . Mucositis Inform patients of the signs and symptoms of mucositis. Instruct patients on ways to reduce the risk of its development, and on ways to maintain nutrition and control discomfort from mucositis if it occurs [ see Warnings and Precautions (5.2) ] .
Dermatologic Reactions Advise patients about the risks for and the signs and symptoms of dermatologic reactions. Instruct patients to immediately notify their healthcare provider if any skin reactions occur [ see Warnings and Precautions (5.3) ] . Tumor Lysis Syndrome Inform patients about the risk of and the signs and symptoms of tumor lysis syndrome.
Patients should be instructed to notify their healthcare provider if they experience these symptoms [ see Warnings and Precautions (5.4) ] . Concomitant Medications Patients should be instructed to inform their healthcare provider if they are taking any concomitant medications including prescription drugs (such as trimethoprim/sulfamethoxazole and probenecid) and nonprescription drugs (such as nonsteroidal anti-inflammatory drugs) [ see Drug Interactions (7.1) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Advise females or reproductive potential to inform their healthcare provider of a known or suspected pregnancy [ see Warnings and Precautions (5.7) and Use in Specific Populations (8.1) ] . Advise females patients of reproductive potential to use effective contraception during treatment with FOLOTYN and for 6 months after the final dose [ see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with FOLOTYN and for at least 3 months after the final dose [ see Use in Specific Populations (8.3) ] Lactation Advise females women not to breastfeed during treatment with FOLOTYN and for 1 week after the final dose [ see Use in Specific Populations (8.2) ] .
Manufactured by: Baxter Oncology GmbH Halle, 33790, Germany Manufactured for: Acrotech Biopharma Inc East Windsor, NJ 08520 USA 1-888-255-6788 FOLOTYN is a registered trademark of Acrotech Biopharma Inc. U.S. Patents: 6,028,071, 7,622,470 and 8,299,078 © Acrotech Biopharma Inc.
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