Drug information of Pralatrexate

Pralatrexate

Drug group:

Pralatrexate is an antimetabolite for the treatment of relapsed or refractory peripheral T-cell lymphoma. It is more efficiently retained in cancer cells than methotrexate.

Mechanism of effect

The selectivity of pralatrexate for cancer cells is based upon the observation that cancer cells generally have an overexpression of reduced folate carrier protein-1 (RTC-1) compared to normal somatic cells. This carrier protein allows the entrance of pralatrexate into the cell. Upon entering the cell, folypolyglutamate synthase FPGS catalyzes the polyglutamination of pralatrexate so that it is retained inside the cell.
Once inside, pralatrexate competitively inhibits dihydrofolate reductase (DHFR) and thymidylate synthase. Subsequent depletion of thymidine monophosphate (TMP) occurs so that the cancer cell is unable to synthesize DNA and RNA. As a result, the cancer cell cannot proliferate and is forced to undergo apoptosis. Pralatrexate is more effective against cells that are actively dividing.

Pharmacodynamic

Pralatrexate is a 10-deazaaminopterin analogue of methotrexate. Compared to methotrexate, pralatrexate binds to RTC-1 with 10-times the affinity and is a more potent substrate for FPGS. As a result, pralatrexate is better internalized and retained in cancer cells and is more cytotoxic.

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

Drug indications

peripheral T-cell lymphoma

Dosage

Adult

Peripheral T-Cell Lymphoma

30 mg/m² IV qweek for 6 week in 7 week cycles

Pediatric

Safety and efficacy not established

Drug contraindications

Hypersensitivity

Alerts

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

Points of recommendation

  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • If you have upset stomach, throwing up, diarrhea, or are not hungry, talk with your doctor. There may be ways to lower these side effects.
  • Mouth irritation and mouth sores are common with pralatrexate. These side effects may happen as early as a few days after getting pralatrexate. Do what your doctor or other health care provider tells you to prevent mouth irritation or mouth sores. Call your doctor if mouth irritation or mouth sores get very bad, bother you, or do not go away.
  • A very bad skin reaction (toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • Patients with cancer who take pralatrexate may be at a greater risk of getting a severe health problem called tumor lysis syndrome (TLS).This may lead to death. Call your doctor right away if you have a fast or abnormal heartbeat; any passing out; trouble passing urine; muscle weakness or cramps; upset stomach, throwing up, diarrhea, or not able to eat; or feel sluggish.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant.
  • Use birth control that you can trust to prevent pregnancy while taking pralatrexate.
  • If you are pregnant or you get pregnant while taking pralatrexate, call your doctor right away.
  • Take folic acid as your doctor tells you before, during, and after using pralatrexate. Talk with your doctor.


Tags

Ask a Pharmacist


User's questions
    No comments yet.