Version July 2025
Note: Initiate vitamin supplements before initial pralatrexate dose: Folic acid 1 to 1.25 mg/day orally beginning 10 days prior to initial pralatrexate dose; continue during treatment and for 30 days after last pralatrexate dose; vitamin B12 1,000 mcg IM within 10 weeks prior to initial pralatrexate dose and every 8 to 10 weeks thereafter (after first dose, subsequent B12 doses may be administered on the same day as pralatrexate). In addition to folic acid and vitamin B12, administration of leucovorin 25 mg orally 3 times daily for 2 consecutive days (total of 6 doses) beginning 24 hours after each pralatrexate dose has also been described to reduce the incidence of mucositis (Ref).
Prior to administering any dose, mucositis should be ≤ grade 1 and ANC should be ≥1,000/mm3; platelets should be ≥100,000/mm3 for the first dose and ≥50,000/mm3 for subsequent doses.
Peripheral T-cell lymphoma, relapsed/refractory: IV: 30 mg/m2 once weekly for 6 weeks of a 7-week treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Cutaneous T-cell lymphoma, including mycosis fungoides and Sezary syndrome, relapsed or refractory (off-label dosing): IV:15 mg/m2 once weekly for 3 weeks of a 4-week treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR 15 to <30 mL/minute/1.73 m2: Initial: Reduce dose to 15 mg/m2; monitor renal function and further reduce dose if necessary based on toxicity.
End-stage renal disease, including dialysis: Avoid use; if the potential benefit outweighs risks, monitor renal function and reduce dose based on toxicity.
Persistent LFT abnormalities may indicate hepatotoxicity requiring dosage modification:
Grade 3: Omit dose; when recovered to ≤ grade 2, resume pralatrexate at a reduced dose (see Dosing: Adjustment for Toxicity).
Grade 4: Discontinue treatment.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Hematologic toxicity:
Platelets:
<50,000/mm3 (for 1-week duration): Omit dose; continue at previous dose if platelets recover within 1 week.
<50,000/mm3 (for 2-week duration): Omit dose; decrease to 20 mg/m2 (10 mg/m2 in patients with eGFR 15 to <30 mL/minute/1.73 m2) if platelets recover within 2 weeks.
<50,000/mm3 (for 3-week duration): Discontinue treatment.
ANC:
500 to 1,000/mm3 without fever (for 1-week duration): Omit dose; continue at previous dose if ANC recovers within 1 week.
500 to 1,000/mm3 with fever or ANC <500/mm3 (for 1-week duration): Omit dose, give filgrastim or sargramostim support; continue at previous dose (with growth factor support) if ANC recovers within 1 week.
500 to 1,000/mm3 with fever or ANC <500/mm3 (recurrent or for 2-week duration): Omit dose and give filgrastim or sargramostim support; decrease to 20 mg/m2 (10 mg/m2 in patients with eGFR 15 to <30 mL/minute/1.73 m2) with growth factor support if ANC recovers within 2 weeks.
500 to 1,000/mm3 with fever or ANC <500/mm3 (second recurrence or for 3-week duration): Discontinue treatment.
Nonhematologic toxicity: Mucositis (on day of treatment):
Grade 2: Omit dose; continue at previous dose when recovers to ≤ grade 1.
Grade 3 or recurrent grade 2: Omit dose and decrease to 20 mg/m2 (10 mg/m2 in patients with eGFR 15 to <30 mL/minute/1.73 m2) when recovers to ≤ grade 1.
Grade 4: Discontinue treatment.
Nonhematologic toxicity (other than mucositis):
Grade 3: Omit dose; decrease to 20 mg/m2 (10 mg/m2 in patients with eGFR 15 to <30 mL/minute/1.73 m2) when recovers to ≤ grade 2.
Grade 4: Discontinue treatment.
Dermatologic reaction, severe: Withhold or discontinue treatment for severe dermatologic reaction.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (30%)
Dermatologic: Night sweats (11%), pruritus (14%), skin rash (15%)
Endocrine & metabolic: Hypokalemia (15%)
Gastrointestinal: Abdominal pain (12%), anorexia (15%), constipation (33%), diarrhea (21%), nausea (40%), stomatitis (70%; grade 3: 17%; grade 4: 4%), vomiting (25%)
Hematologic & oncologic: Anemia (34%; grade 3: 15%; grade 4: 2%), leukopenia (11%; grade 3: 3%; grade 4: 4%), neutropenia (24%; grade 3: 13%; grade 4: 7%), thrombocytopenia (41%; grade 3: 14%; grade 4: 19%)
Hepatic: Increased serum transaminases (13%)
Nervous system: Fatigue (36%)
Neuromuscular & skeletal: Back pain (11%), limb pain (12%)
Respiratory: Cough (28%), dyspnea (19%), epistaxis (26%), pharyngolaryngeal pain (14%)
Miscellaneous: Fever (32%)
1% to 10%:
Cardiovascular: Tachycardia (10%)
Endocrine & metabolic: Dehydration
Hematologic & oncologic: Febrile neutropenia
Infection: Sepsis
Neuromuscular & skeletal: Asthenia (10%)
Respiratory: Upper respiratory tract infection (10%)
<1%, postmarketing, and/or case reports: Dermal ulcer, exfoliation of skin, toxic epidermal necrolysis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to pralatrexate or any component of the formulation
Concerns related to adverse effects:
• Bone marrow suppression: Pralatrexate may cause thrombocytopenia, neutropenia, and anemia.
• Dermatologic reactions: Severe and potentially fatal dermatologic reactions, including skin exfoliation, ulceration, and toxic epidermal necrolysis, have been reported. Skin reaction may be progressive; severity may increase with continued treatment, and may also involve skin and subcutaneous tissues which are affected by lymphoma.
• Hepatotoxicity: Hepatotoxicity and LFT abnormalities have been observed with use. Persistent abnormalities may indicate hepatotoxicity.
• Mucositis: Pralatrexate may cause mucositis (includes stomatitis or mucosal inflammation of GI and genitourinary tracts).
• Tumor lysis syndrome: Pralatrexate may cause tumor lysis syndrome.
Disease-related concerns:
• Renal impairment: Patients with severe renal impairment are at higher risk for increased exposure and toxicity. Serious adverse reactions, including toxic epidermal necrolysis and mucositis, were reported in patients with end-stage renal disease undergoing dialysis.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Folotyn: 20 mg/mL (1 mL); 40 mg/2 mL (2 mL)
Generic: 20 mg/mL (1 mL [DSC]); 40 mg/2 mL (2 mL [DSC])
Yes
Solution (Folotyn Intravenous)
20 mg/mL (per mL): $8,891.75
40 mg/2 mL (per mL): $8,891.75
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Folotyn: 20 mg/mL (1 mL)
IV: Administer IV push (undiluted) over 3 to 5 minutes into the line of a free-flowing normal saline IV.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Peripheral T-cell lymphoma, relapsed or refractory: Treatment of relapsed or refractory peripheral T-cell lymphoma.
PRALAtrexate may be confused with methotrexate, PEMEtrexed, pralsetinib, raltitrexed
Folotyn may be confused with Focalin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of BCRP;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nonsteroidal Anti-Inflammatory Agents: May increase serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider Therapy Modification
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Probenecid: May increase serum concentration of PRALAtrexate. Management: Avoid coadministration of pralatrexate with probenecid. If coadministration cannot be avoided, closely monitor for increased pralatrexate serum concentrations or possible toxicity with concomitant use of probenecid. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Pyrimethamine: May increase adverse/toxic effects of PRALAtrexate. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Salicylates: May increase serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider Therapy Modification
Sapropterin: PRALAtrexate may decrease serum concentration of Sapropterin. Specifically, pralatrexate may decrease tissue concentrations of tetrahydrobiopterin. Risk C: Monitor
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Sulfamethoxazole: May increase serum concentration of PRALAtrexate. More specifically, sulfamethoxazole may decrease excretion of pralatrexate. Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Trimethoprim: May increase serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Risk C: Monitor
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Evaluate pregnancy status prior to use in patients who may become pregnant.
Patients who may become pregnant should use effective contraception during therapy and for 6 months after the last pralatrexate dose. Patients with partners who may become pregnant should use effective contraception during therapy and for 3 months after the last dose of pralatrexate.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to pralatrexate may cause fetal harm.
It is not known if pralatrexate is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during therapy and for 1 week after the last pralatrexate dose.
CBC with differential (baseline and weekly), serum chemistries, including renal and LFTs (prior to the first and fourth doses in each cycle). Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor mucositis severity (baseline and weekly); monitor for signs of tumor lysis syndrome and for dermatologic reactions.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Pralatrexate is an antifolate analog; it inhibits DNA, RNA, and protein synthesis by selectively entering cells expressing reduced folate carrier (RFC-1), is polyglutamylated by folylpolyglutamate synthetase (FPGS) and then inhibits dihydrofolate reductase (DHFR) by competing for the DHFR-folate binding site.
Distribution: S-diastereomer: 105 L; R-diastereomer: 37 L.
Protein binding: ~67%.
Metabolism: Not significantly metabolized by phase I hepatic isoenzymes or phase II glucuronidases.
Half-life elimination: 12 to 18 hours.
Excretion: Urine (~34% as unchanged drug; parent drug [racemic pralatrexate]: ~39%); Feces (34%); Respiratory (10% [exhaled]).
Clearance: S-diastereomer: 417 mL/minute; R-diastereomer: 191 mL/minute.
Altered kidney function: The mean fractions of a dose excreted as unchanged drug in the urine decreases with declining renal function.
