Dosing and uses of Folotyn (pralatrexate)
Adult dosage forms and strengths
IV solution
- 20mg/mL
- 40mg/2mL
Peripheral T-Cell Lymphoma
Indicated for relapsed or refractory PTCL
30 mg/m² IV qweek for 6 week in 7 week cycles
Dosage modifications
- Before administering any pralatrexate dose, mucositis should be ≤Grade 1, platelet count should be ≥100,000/mcL (first dose) and ≥50,000/mcL (subsequent doses), and absolute neutrophil count (ANC) should be ≥1,000/mcL
- See Prescribing Information for omitting or reducing dose based on patient tolerance
- Omitted doses will not be made up at the end of the cycle
- Once dose reduction occurs for toxicity, do not re-escalate
Renal Impairment
eGFR ≥ 30 mL/min/1.73 m²: Dose adjustment not necessary
Estimated GFR (eGFR) 15 to <30 mL/min/1.73 m²: Reduce initial dose to 15 mg/m²; if dose reduction necessary because of toxicity, reduce each dose to 10 mg/m²
End-stage renal disease (ESRD): Avoid use unless potential benefits outweigh risks
Hepatic Impairment
Grade 3 (AST or ALT >5 to 20 times ULN or bilirubin >3 to 10 times ULN): Omit dose; decrease to 20 mg/m m² when recovers to grade 2
Grade 4 (AST or ALT >20 times ULN or bilirubin >10 times ULN): Discontinue treatment
Orphan Indications
Diffuse large B-cell lymphoma
Advanced or metastatic transitional cell urinary bladder carcinoma
Follicular lymphoma
Orphan indications sponsor
- Allos Therapeutics, Inc; 11080 CirclePoint Road; Westminster, CO
Administration
Infuse IV over 3-5 minute via side port of free flowing 0.9% NaCl IV line
Dose omissions and/or dose reductions may be needed to manage adverse drug reactions
Pretreatment vitamin supplementation
- Folic acid: Initiate 1-1.25 mg PO qDay 10 days before first pralatrexate dose; continue daily folic acid during entire treatment course and for 30 days after last pralatrexate dose
- Vitamin B12: 1 mg IM within 10 weeks before first pralatrexate dose and q8-10 wk thereafter
Pediatric dosage forms and strengths
Safety and efficacy not established
Folotyn (pralatrexate) adverse (side) effects
>10%
Inflammatory disease of mucous membrane, Any grade (70% )
Thrombocytopenia, Any grade (41% )
Nausea (40% )
Fatigue (36% )
Anemia, Any grade (34% )
Constipation (33% )
Pancytopenia, Thrombocytopenia, Grade 3/4 (33% )
Edema (30% )
Cough (28% )
Neutropenia, Any grade (24% )
Inflammatory disease of mucous membrane, Grade 3/4 (21% )
Neutropenia, Grade 3/4 (20% )
Dyspnea (19% )
Anemia (17% )
1-10%
Febrile neutropenia (>3% )
Sepsis (>3% )
Postmarketing Reports
Skin exfoliation, ulceration, and toxic epidermal necrolysis
Warnings
Contraindications
Hypersensitivity
Cautions
Supplement with vitamin B12 and folic acid to decrease mucositis
Treatment interruption or dose reduction to 20 mg/sq.meter may be required with severe mucositis, thrombocytopenia, or elevated liver function tests
Caution with moderate-to-severe renal impairment (higher risk for toxicity); monitor for systemic toxicity and adjust dose accordingly
Reports of severe dermatologic reactions including skin exfoliation, ulceration, and toxic epidermal necrolysis (withhold or discontinue treatment)
Avoid breast feeding
Probenecid decreases renal elimination of pralatrexate
Pregnancy and lactation
Pregnancy category: d
Lactation: Unknown if excreted in breast milk; do not breast feed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Folotyn (pralatrexate)
Mechanism of action
Folate inhibitor
Pharmacokinetics
Clearance: 417 mL/min (S-diastereomer); 191 mL/min (R-diastereomer)
Half-life: 12-18 hr
Vd: 105 L (S-diastereomer); 37 L (R-diastereomer)
Protein Bound: 67%
Metabolism: Not significantly metabolized by CYP450 or hepatic glucuronidases
Excretion: (urine) 34% unchanged
Administration
IV Preparation
Do not dilute
Contains no preservatives
Clear, yellow solution; inspect for discoloration/particulate matter
IV Administration
Infuse IV over 3-5 min via side port of free flowing 0.9% NaCl IV line
Extravasation Management
Terminate injection or infusion immediately & aspirate back as much as possible
Apply warm pack for 15-20 min QID & elevate
Storage
Store intact vials under refrigeration at 2-8°C
Store in original carton to protect from light
Intact, unopened vials stable at room temperature for 72 hr if protected from light (discard after 72 hr)
