Vesanoid (Oral)

Patients with acute promyelocytic leukemia (APL) can have severe adverse reactions to tretinoin. Tretinoin should therefore be administered only to patients with APL under the strict supervision of a physician who is experienced in the management of patients with acute leukemia and in a facility with laboratory and supportive services sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity, including respiratory compromise. Use of tretinoin requires a favorable risk benefit profile.Retinoic Acid-APL Syndrome: Patients treated with tretinoin have experienced retinoic acid-APL (RA-APL) syndrome characterized by fever, dyspnea, acute respiratory distress, weight gain, radiographic pulmonary infiltrates, pleural and pericardial effusions, edema, and hepatic, renal, and multi-organ failure. RA-APL has been accompanied by impaired myocardial contractility and episodic hypotension. It has been observed with or without concomitant leukocytosis. Endotracheal intubation and mechanical ventilation have been required in some cases due to progressive hypoxemia, and several patients have expired with multi-organ failure. RA-APL may occur during the first month of treatment, with some cases reported following the first dose of tretinoin. High-dose steroids given at the first suspicion of the RA-APL syndrome appear to reduce morbidity and mortality. At the first signs of RA-APL (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg IV administered every 12 hours for 3 days or until the resolution of symptoms) should be immediately initiated, irrespective of the leukocyte count. The majority of patients do not require termination of tretinoin therapy during treatment of the RA-APL syndrome. However, in cases of moderate and severe RA-APL, consider temporary interruption of therapy.Leukocytosis at Presentation and Rapidly Evolving Leukocytosis During Tretinoin Treatment: Rapidly evolving leukocytosis may occur with therapy. Patients who present with high WBC at diagnosis (greater than 5x10(9)/L) have an increased risk of a further rapid increase in WBC counts. Rapidly evolving leukocytosis is associated with a higher risk of life-threatening complications. If signs and symptoms of the RA-APL syndrome are present together with leukocytosis, treatment with high-dose steroids should be initiated immediately. Some investigators routinely add chemotherapy to tretinoin treatment in the case of patients presenting with a WBC count of greater than 5x10(9)/L or in the case of a rapid increase in WBC count for patients leukopenic at start of treatment, and have reported a lower incidence of the RA-APL syndrome. Consideration could be given to adding full-dose chemotherapy (including an anthracycline if not contraindicated) to the tretinoin therapy on day 1 or 2 for patients presenting with a WBC count of greater than 5x10(9)/L, or immediately, for patients presenting with a WBC count of less than 5x10(9)/L, if the WBC count reaches greater than or equal to 6x10(9..