Drug Notebook

FDA Alerts

    Limit to Qualified Personnel
  • Administer only under the supervision of a qualified clinician experienced in the management of patients with acute leukemia.
  • Appropriate diagnostic and treatment facilities must be readily available in case the patient develops severe toxicity, including respiratory compromise.
  • Use only when the potential benefits are thought to outweigh the possible risks of therapy.

    Retinoic Acid-APL (RA-APL) Syndrome
  • Clinical manifestations of the syndrome (fever, dyspnea, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions), with or without leukocytosis, have occurred in about 25% of patients.
  • Occasionally accompanied by impaired myocardial contractility and episodic hypotension.
  • Progessive hypoxemia has required endotracheal intubation and mechanical ventilation and may be fatal (due to multiorgan failure).
  • High-dose corticosteroid therapy administered at first suspicion of the syndrome may reduce morbidity or mortality. (See RA-APL Syndrome under Cautions.)

    Leukocytosis
  • Rapidly evolving leukocytosis occurs in approximately 40% of patients and is associated with an increased risk of life-threatening complications.
  • High leukocyte count (i.e., >5000/mm3) at diagnosis increases risk of further rapid increase of leukocyte count.
  • Initiate high-dose corticosteroid treatment immediately if leukocytosis and signs or symptoms of RA-APL syndrome are present together.
  • Consider adding full-dose chemotherapy (including anthracycline) to tretinoin. (See Leukocytosis under Cautions.)

    Teratogenic Effects
  • Known teratogen; special precautions and instruction are necessary in women of childbearing potential or pregnant women receiving the drug. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
  • Inform patients of the risks of fetal harm and contraceptive failure.

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tretinoin
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(TRET i noin)

Uses

Acute Promyelocytic Leukemia

Used to induce remission in acute promyelocytic leukemia (APL), French-American-British classification M3 including the M3 variant, characterized by the presence of certain genetic markers (i.e., 15;17 chromosomal translocation and/or PML/RAR-α gene) in patients with relapsed or refractory disease following anthracycline-based chemotherapy or in patients for whom anthracycline therapy is contraindicated.

Most clinicians recommend addition of tretinoin to induction combination chemotherapy (anthracycline-based) as initial† treatment for APL in patients with previously untreated disease.

May initiate tretinoin therapy based on the morphologic diagnosis of APL, but perform cytogenetic evaluation to confirm presence of the 15;17 translocation, and if absent, perform molecular diagnostic testing for the PML/RAR-α fusion protein.

May be ineffective when these genetic markers are absent; consider alternative therapy.

Dosage and Administration

General

  • Tretinoin apparently induces its own metabolism; clinical failure may be related to a lack of sustained effective concentrations during prolonged treatment. (See Plasma Concentrations under Pharmacokinetics.) Increasing dosage to compensate does not increase response.

Administration

Oral Administration

Administer orally in 2-equally divided doses.

Manufacturer makes no specific recommendations regarding administration with meals; however, food has enhanced absorption of other retinoids. (See Absorption under Pharmacokinetics.)

Dosage

Discontinue tretinoin and consider alternative treatment if the presence of 15;17 chromosomal translocation and/or PML/RAR-α gene is not confirmed and the disease is not responding.

Unless contraindicated, administer consolidation and/or maintenance chemotherapy to all patients following tretinoin induction therapy.

Consider temporary discontinuance if serum transaminase concentrations >5 times the ULN. (See Hepatic Effects under Cautions.)

Pediatric Patients

Acute Promyelocytic Leukemia (APL)

Oral

45 mg/m2 daily administered in 2 evenly divided doses.

Continue until 30 days after complete remission is achieved, or for a total of 90 days, whichever occurs first. Some clinicians recommend continuing until complete remission is achieved, or for a total of 90 days (whichever occurs first).

Consider dosage reduction if serious or intolerable drug toxicity; however, safety and efficacy of dosages <45 mg/m2 daily have not been established.

Adults

APL

Oral

45 mg/m2 daily administered in 2 evenly divided doses.

Continue until 30 days after complete remission is achieved, or for a total of 90 days, whichever occurs first. Some clinicians recommend continuing until complete remission is achieved, or for a total of 90 days (whichever occurs first).

Prescribing Limits

Pediatric Patients

APL

Oral

Safety and efficacy of dosages <45 mg/m2 daily have not been established.

Maximum duration: 30 days after complete remission, up to 90 days of therapy.

Adults

APL

Oral

Maximum duration: 30 days after complete remission, up to 90 days of therapy.

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