pralatrexate

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.

Adv. Reactions/Side Effects ⬆ ⬇

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

Interactions ⬆ ⬇

Drug-drug:

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

Availability ⬆ ⬇

Solution for injection: 20 mg/mL

Route/Dosage ⬆ ⬇

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).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: folic acid analogues

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	45 days‡	unknown	unknown

‡median time to first response.

Patient/Family Teaching ⬆ ⬇

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 mo and males with female partners of reproductive potential to use effective contraception for 3 mo 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇