Indications

Tretinoin capsules are indicated for the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene ... Read more Tretinoin capsules are indicated for the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated. Tretinoin is for the induction of remission only. The optimal consolidation or maintenance regimens have not been defined, but all patients should receive an accepted form of remission consolidation and/or maintenance therapy for APL after completion of induction therapy with Tretinoin.

Composition

Pharmacology

Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. In APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

Dosage & Administration

The recommended dose is 45 mg/m2/day administered as two evenly divided doses until complete remission is documented. Therapy should be discontinued 30 days after achievement of complete remission or after 90 days of treatment, whichever occurs first. If after initiation of treatment of Tretinoin the presence of the t(15;17) translocation is not confirmed by cytogenetics and/or by polymerase chain reaction studies and the patient has not responded to Tretinoin, alternative therapy appropriate for acute myelogenous leukemia should be considered. Tretinoin is for the induction of remission only. Optimal consolidation or maintenance regimens have not been determined. All patients should, therefore, receive a standard consolidation and/or maintenance chemotherapy regimen for APL after induction therapy with Tretinoin, unless otherwise contraindicated.

Contraindications

Tretinoin is contraindicated in patients with a known hypersensitivity to Tretinoin, any of its components, or other retinoids. Tretinoin should not be given to patients who are sensitive to parabens, which are used as preservatives in the gelatin capsule.

Side Effects

Virtually all patients experience some drug-related toxicity, especially headache, fever, weakness, and fatigue. These adverse effects are seldom permanent or irreversible nor do they usually require interruption of therapy. Some of the adverse events are common in patients with APL, including hemorrhage, infections, gastrointestinal hemorrhage, disseminated intravascular coagulation, pneumonia, septicemia, and cerebral hemorrhage. The following describes the adverse events, regardless of drug relationship, that were observed in patients treated with Tretinoin.

Pregnancy & Lactation

Pregnancy Category D. Tretinoin has teratogenic and embryotoxic effects in mice, rats, hamsters, rabbits and pigtail monkeys, and may be expected to cause fetal harm when administered to a pregnant woman. Tretinoin causes fetal resorptions and a decrease in live fetuses in all animals studied. Although experience with humans administered Tretinoin is extremely limited, increased spontaneous abortions and major human fetal abnormalities related to the use of other retinoids have been documented in humans. Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from Tretinoin in nursing infants, mothers should discontinue nursing prior to taking this drug.

Precautions & Warnings

Tretinoin has potentially significant toxic side effects in APL patients. Patients undergoing therapy should be closely observed for signs of respiratory compromise and/or leukocytosis. Supportive care appropriate for APL patients, eg, prophylaxis for bleeding, prompt therapy for infection, should be maintained during therapy with Tretinoin. There is a risk of thrombosis (both venous and arterial) which may involve any organ system, during the first month of treatment. Therefore, caution should be exercised when treating patients with the combination of Tretinoin and anti-fibrinolytic agents, such as tranexamic acid, aminocaproic acid or aprotinin. The ability to drive or operate machinery might be impaired in patients treated with Tretinoin, particularly if they are experiencing dizziness or severe headache. Microdosed progesterone preparations ("minipill") may be an inadequate method of contraception during treatment with Tretinoin.

Therapeutic Class

Oral Retinoid preparations

Storage Conditions

Store at 15° to 30°C. Protect from light.