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.
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.)
Consider temporary discontinuance in patients with moderate or severe retinoic acid-APL syndrome. (See RA-APL Syndrome under Cautions.)
Pediatric Patients
Acute Promyelocytic Leukemia
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
Acute Promyelocytic Leukemia
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
Acute Promyelocytic Leukemia
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
Acute Promyelocytic Leukemia
Oral
Maximum duration: 30 days after complete remission, up to 90 days of therapy.
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