FOLOTYN
Clinical safety rating
cautionComprehensive clinical and safety monograph for FOLOTYN (FOLOTYN).
Comprehensive clinical and safety monograph for FOLOTYN (FOLOTYN).
Relapsed or refractory peripheral T-cell lymphoma (PTCL)
FOLOTYN (pralatrexate) is a folate analogue metabolic inhibitor that competes for the reduced folate carrier and folylpolyglutamate synthetase, leading to intracellular accumulation of polyglutamated metabolites that inhibit dihydrofolate reductase (DHFR) and thymidylate synthase, thereby disrupting DNA synthesis and cell proliferation.
| Metabolism | Pralatrexate is primarily metabolized via hepatic metabolism; specific enzymes not fully characterized. It is not a significant substrate for CYP450 enzymes. |
| Excretion | Primarily renal excretion (approximately 80% of the dose recovered in urine over 24 hours, with about 60% as unchanged drug); biliary/fecal elimination accounts for <1%. |
| Half-life | Terminal elimination half-life is approximately 4–6 hours; clinical context: supports weekly dosing schedule. |
| Protein binding | Approximately 67% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution at steady state is approximately 0.5 L/kg (range 0.3–0.7 L/kg), indicating distribution into total body water with some tissue binding. |
| Bioavailability | Only intravenous administration is approved; oral bioavailability has not been established (not for oral use). |
| Onset of Action | Intravenous: Clinical response observed within 2–4 weeks depending on disease progression and individual patient factors. |
| Duration of Action | Duration of clinical effect is variable, typically lasting 1–2 weeks post-dose; repeated weekly dosing required for sustained suppression. |
| Molecular Weight | 477.45 |
3.0 mg/m2 intravenously over 3-5 minutes on days 1, 8, and 15 of a 28-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment recommended; use caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh A: 2.0 mg/m2. Child-Pugh B: 1.5 mg/m2. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustments; monitor for renal function and toxicity as elderly patients may have reduced organ function. |
| 1st trimester | Teratogenic in animal studies; avoid use during first trimester unless absolutely necessary. |
| 2nd trimester | May cause fetal harm; use only if potential benefit justifies risk to fetus. |
| 3rd trimester | May cause fetal harm; use only if potential benefit justifies risk to fetus. |
Clinical note
Comprehensive clinical and safety monograph for FOLOTYN (FOLOTYN).
| Placental transfer | Pralatrexate is a folate analogue and is expected to cross the placenta based on its molecular weight and structural similarity to methotrexate, which is known to cross the placenta. |
| Breastfeeding | It is not known whether pralatrexate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women should discontinue breastfeeding during treatment and for at least 7 days after the last dose. |
| Lactation Rating | L5 - Avoid |
| Teratogenic Risk | FOLOTYN (pralatrexate) is a folate analog metabolic inhibitor; based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregnant woman. In animal reproduction studies, pralatrexate caused embryo-fetal toxicity and malformations at doses below the recommended human dose. There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk to a fetus. During first trimester: high risk of teratogenicity (neural tube defects, cardiovascular malformations). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and fetal death. |
| Fetal Monitoring | Monitor complete blood counts, including platelets, at baseline and weekly during treatment. Monitor hepatic function (AST, ALT, total bilirubin) and renal function (serum creatinine) regularly. For pregnant patients exposed to FOLOTYN, perform fetal ultrasound monitoring for growth and amniotic fluid volume; consider referral to maternal-fetal medicine specialist. |
| Fertility Effects | Based on animal studies, FOLOTYN may impair fertility in males and females of reproductive potential. In humans, the effect on fertility is unknown; however, given its mechanism as an antifolate, it may cause reduced spermatogenesis or oogenesis. |
■ FDA Black Box Warning
WARNING: FOLOTYN may cause severe or fatal mucositis, thrombocytopenia, and other hematologic toxicities. Administer with close monitoring, and manage with dose modifications and supportive care as needed.
| Serious Effects |
Hypersensitivity to pralatrexate or any component of the formulationConcurrent administration with folic acid or vitamin B12 deficiencySevere hepatic impairment
| Precautions | Mucositis, hematologic toxicity (including thrombocytopenia, neutropenia, anemia), dermatologic reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), tumor lysis syndrome, hepatotoxicity, and renal toxicity. Monitor complete blood counts, liver function, renal function, and mucositis. Dose adjustments required for toxicity. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction leading to increased toxicity. No other specific food restrictions. |
| Clinical Pearls | Administer intramuscularly; rotate injection sites. Premedicate with corticosteroid, antihistamine, and antipyretic to reduce infusion reactions. Monitor for tumor lysis syndrome, hepatotoxicity, and myelosuppression. Dose adjustment required for renal impairment (CrCl <50 mL/min). Contraindicated in pregnancy. |
| Patient Advice | This medicine is given as an injection into a muscle, usually once weekly. · You may receive medications before your dose to prevent allergic reactions. · Report any signs of infection, unusual bleeding, or bruising promptly. · Avoid pregnancy during treatment; use effective contraception. · Limit alcohol intake to reduce liver strain. · Avoid grapefruit and grapefruit juice as they may increase side effects. |
Loading safety data…