DROXIA

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE DROXIA is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises. DROXIA is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises. (1) Dosage and administration 2 DOSAGE AND ADMINISTRATION Initial dose: 15 mg/kg once daily. Monitor the patient's blood count every two weeks. (2.1) The dose may be increased by 5 mg/kg/day every 12 weeks until a maximum tolerated dose or 35 mg/kg/day is reached if blood counts are in an acceptable range. (2.1) The dose is not increased if blood counts are between the acceptable range and toxic. Discontinue DROXIA until hematologic recovery if blood counts are considered toxic. Treatment may then be resumed after reducing the dose by 2.5 mg/kg/day from the dose associated with hematological toxicity. (2.1) Renal impairment: Reduce the dose of DROXIA by 50% in patients with creatinine clearance less than 60 mL/min. (2.2 , 8.6 , 12.3) 2.1 Dosing Information Table 1: Dosing Recommendation Based on Blood Count Dosing Regimen Dose Dose Modification Criteria Monitoring Parameters Initial Recommended Dosing 15 mg/kg/day as a single dose once daily based on the patient's actual or ideal weight, whichever is less. Monitor the patient's blood count every 2 weeks [see Warnings and Precautions ( 5.1 )]. Dosing Based on Blood Counts In an acceptable range Increase dose 5 mg/kg/day every 12 weeks Maximal dose: 35 mg/kg/day* *Maximal dose is the highest dose that does not produce toxic blood counts over 24 consecutive weeks. Increase dosing only if blood counts are in an acceptable range. Do not increase if myelosuppression occurs. Blood Counts Acceptable Range neutrophils ≥2500 cells/mm 3 platelets ≥95,000/mm 3 hemoglobin >5.3 g/dL reticulocytes ≥95,000/mm 3 if the hemoglobin concentration <9 g/dL Between acceptable and toxic range Do not increase dose. If blood counts are considered toxic , discontinue DROXIA until hematologic recovery. Blood Counts Toxic Range neutrophils <2000 cells/mm 3 platelets <80,000/mm 3 hemoglobin <4.5 g/dL reticulocytes <80,000/mm 3 if the hemoglobin concentration <9 g/dL Dosing After Hematologic Recovery Reduce dose by 2.5 mg/kg/day. Reduce the dose from the dose associated with hematologic toxicity. May titrate up or down every 12 weeks in 2.5 mg/kg/day increments. The patient should be at a stable dose with no hematologic toxicity for 24 weeks. Discontinue the treatment permanently if a patient develops hematologic toxicity twice. Swallow DROXIA capsules whole. Do NOT open, break, or chew capsules because DROXIA is a cytotoxic drug. Patients must be able to follow directions regarding drug administration and their monitoring and care. Fetal hemoglobin (HbF) levels may be used to evaluate the efficacy of DROXIA in clinical use. Obtain HbF levels every three to four months. Monitor for an increase in HbF of at least two-fold over the baseline value. DROXIA causes macrocytosis, which may mask the incidental development of folic acid deficiency. Prophylactic administration of folic acid is recommended. DROXIA is a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15) ]. 2.2 Dose Modifications for Renal Impairment Reduce the dose of DROXIA by 50% in patients with creatinine clearance of less than 60 mL/min or with end-stage renal disease (ESRD) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Creatinine clearance values were obtained using 24-hour urine collections. * On dialysis days, administer DROXIA to patients with ESRD following hemodialysis. Creatinine Clearance (mL/min) Recommended DROXIA Initial Dose (mg/kg once daily) ≥60 15 <60 or ESRD* 7.5 Monitor the hematologic parameters closely in these patients. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Hemolytic anemia: Monitor blood counts throughout treatment. If hemolysis persists, discontinue DROXIA. ( 5.2 ) Embryo-Fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3) Vasculitic toxicities: Institute treatment and discontinue DROXIA if this occurs. (5.5) Live Vaccinations: Avoid live vaccine use in a patient taking DROXIA. (5.6) Risks with concomitant use of antiretroviral drugs: Pancreatitis, hepatotoxicity, and neuropathy have occurred. Monitor for signs and symptoms in patients with HIV infection using antiretroviral drugs; discontinue DROXIA and implement treatment. (5.7) 5.1 Myelosuppression Hydroxyurea causes severe myelosuppression. Treatment with DROXIA should not be initiated if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytope