pralatrexate

pra-le-TREX-ate

Therapeutic Classification: antineoplastics

Pharmacologic Classification: folic acid analogues

High Alert

Treatment relapsed/refractory peripheral T-cell lymphoma.

Interferes with folic acid metabolism by acting as a folate analogue metabolic inhibitor that competitively inhibits dihydrofolate reductase; also acts as a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. Result is inhibition of DNA synthesis.

Therapeutic effects:

Death of rapidly replication cells, particularly malignant ones.

Absorption: IV administration results in complete bioavailability.

Distribution: .

Metabolism/Excretion: Some metabolism by the liver; 34% excreted unchanged in urine.

Half-Life: 12–18 hr.

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	45 days‡	unknown	unknown

‡median time to first response.

Contraindicated in:

End-stage renal disease (↑ risk of toxicity);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (↑ risk of toxicity; ↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Consider age-related in renal function.

CV: edema, tachycardia

Derm: exfoliation, pruritus, rash, TOXIC EPIDERMAL NECROLYSIS, ulceration

EENT: epistaxis, pharyngolaryngeal pain

F and E: dehydration, hypokalemia

GI: mucositis, nausea, ↑liver enzymes, abdominal pain, anorexia, constipation, diarrhea, vomiting

Hemat: neutropenia, thrombocytopenia, anemia

MS: back pain, extremity pain

Neuro: fatigue

Resp: dyspnea, cough

Misc: fever, sepsis, night sweats, tumor lysis syndrome

Drug-drug:

Probenecid, NSAIDs, and trimethoprim/sulfamethoxazole may ↓ clearance and ↑ blood levels and the risk of toxicity.

IV (Adults ): 30 mg/m² once weekly for 6 wk in 7-wk cycles until disease progresses or unacceptable toxicity occurs (supplemental intramuscular vitamin B₁₂ 1 mg every 8–10 wk and folic acid 1.0–1.25 mg orally on a daily basis is required).

Renal Impairment

IV (Adults ): eGFR 15–29 mL/min/1.73 m²: 15 mg/m² once weekly for 6 wk in 7-wk cycles until disease progresses or unacceptable toxicity occurs (supplemental intramuscular vitamin B₁₂ 1 mg every 8–10 wk and folic acid 1.0–1.25 mg orally on a daily basis is required).

Solution for injection: 20 mg/mL

Monitor BP, pulse, respiratory rate, and temperature frequently during administration. Report significant changes.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
Assess oral mucosa prior to and wkly for development of mucositis. Increased dosing interval and/or decreased dose is recommended if lesions are painful or interfere with nutrition. Mucositis must be ≤Grade 1 for administration of pralatrexate. If Grade 2, omit dose and continue prior dose when mucositis recovers to ≤Grade 1. If Grade 2 recurs or Grade 3 occurs, omit dose and decrease next pralatrexate dose to 20 mg/m² or 10 mg/m²for patients with severe renal impairment when mucositis recovers to ≤Grade 1.If Grade 4, stop therapy.
Assess for rash periodically during therapy. May cause toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
Monitor for tumor lysis syndrome (malignant disease progression, high WBC counts, hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcamia and/or dehydration); treat symptomatically.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Monitor CBC and differential prior to and wkly during therapy. May cause thrombocytopenia, neutropenia, and anemia. Platelet count should be ≥100,000 cells/mm³ for first dose and ≥50,000 cells/mm³ for all subsequent doses. If platelet count <50,000 cells/mm³, for 1 wk, omit dose and continue prior dose upon restart. If platelet count <50,000 cells/mm³, for 2 wks, omit dose and decrease pralatrexate dose to 20 mg/m²or 10 mg/m²for patients with severe renal impairment upon restart. If platelet count <50,000 cells/mm³, for 3 wks, stop therapy.
- Absolute neutrophil count (ANC) should be ≥1,000 cells/mm³prior to administering each dose of pralatrexate. If ANC 500–1,000 cells/mm³ and no fever for 1 wk, omit dose and continue prior dose upon restart. If ANC 500–1,000 cells/mm³ with fever or ANC <500 cells/mm³ for 1 wk , omit dose, give filgrastim or sargramostim and continue prior dose with filgrastim or sargramostim upon restart. If ANC 500–1,000 cells/mm³ with fever or ANC <500 cells/mm³ for 2 wks or recurrence, omit dose, give filgrastim or sargramostim and decrease pralatrexate dose to 20 mg/m² or 10 mg/m²for patients with severe renal impairment with filgrastim or sargramostim upon restart. If ANC 500–1,000 cells/mm³ with fever or ANC <500 cells/mm³ for 3 wks or 2nd recurrence, stop therapy.
- For all other treatment-related toxicities: if Grade 3, omit dose and upon recovery to Grade 2, decrease dose to 20 mg/m²or 10 mg/m²for patients with severe renal impairment. If Grade 4, stop therapy.
- Monitor serum chemistry, including liver and renal function prior to the first and fourth doses of each cycle during therapy.

Do not confuse pralatrexate with pemetrexed.
Patients should take oral folic acid 1–1.25 mg daily starting 10 days prior to first dose of pralatrexate, through full course of therapy, and for 30 days after completion of therapy. Patients should also receive vitamin B₁₂ 1 mg IM no more than 10 wks prior to first dose of pralatrexate and every 8–10 wks during therapy; may be given on same day as pralatrexate.

IV Administration:

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. Clarify orders that do not include generic and brand names.
Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers.
Withdraw calculated dose into syringe for immediate use. Do not dilute. Solution is clear yellow; do not administer solutions that are discolored or contain particulate matter. For single use only; discard unused portion. Stable if stored in original carton for 72 hrs at room temperature; protect from light.
Rate: Administer as an IV push over 3–5 minutes via side port of a free-flowing 0.9% NaCl injection.

Advise patient to read the Patient Information that comes with medication prior to each dose.
Instruct patient to notify health care professional promptly if rash, fever; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; weakness; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush, rinse mouth with water after eating and drinking, and confer with health care professional if mouth pain interferes with eating. Pain may require treatment with opioid analgesics.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mos and males with female partners of reproductive potential to use effective contraception for 3 mos after last dose of therapy. Advise patient to avoid breastfeeding for 1 wk after last dose of therapy. Advise patient to notify health care professional if pregnancy is planned or suspected.
Emphasize the need for periodic lab tests to monitor for side effects.

Decreased T-cell count in patients with T-cell lymphoma.

Folotyn

NDC Code

48818- Allos Therapeutics
- 48818-001- Folotyn
  - 48818-001-01- 1 VIAL, SINGLE-USE in 1 CARTON (48818-001-01) > 1 mL in 1 VIAL, SINGLE-USE

48818- Allos Therapeutics
- 48818-001- Folotyn
  - 48818-001-02- 1 VIAL, SINGLE-USE in 1 CARTON (48818-001-02) > 2 mL in 1 VIAL, SINGLE-USE

72893- Acrotech Biopharma LLC
- 72893-003- Folotyn
  - 72893-003-01- 1 VIAL in 1 CARTON (72893-003-01) > 1 mL in 1 VIAL

72893- Acrotech Biopharma LLC
- 72893-005- Folotyn
  - 72893-005-01- 1 VIAL in 1 CARTON (72893-005-01) > 2 mL in 1 VIAL

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