2.1 Recommended Dosage
Administer the recommended pediatric dose of 52 mg/m2 as an intravenous infusion over 2 hours daily for 5 consecutive days.
Treatment cycles are repeated following recovery or return to baseline organ function, approximately every 2 to 6 weeks. The dosage is based on the patient's body surface area (BSA), calculated using the actual height and weight before the start of each cycle. To prevent drug incompatibilities, no other medications should be administered through the same intravenous line.
Provide supportive care, such as intravenous fluids, antihyperuricemic treatment, and alkalinize urine throughout the 5 days of Clolar administration to reduce the effects of tumor lysis and other adverse events.
Discontinue Clolar if hypotension develops during the 5 days of administration.
Monitor renal and hepatic function during the 5 days of Clolar administration [see Warnings and Precautions (5.6, 5.7)].
Monitor patients taking medications known to affect blood pressure. Monitor cardiac function during administration of Clolar.
Reduce the dose by 50% in patients with creatinine clearance (CrCL) between 30 and 60 mL/min. There is insufficient information to make a dosage recommendation in patients with CrCL less than 30 mL/min [see Use in Specific Populations (8.7)].
2.2 Supportive Medications and Medications to Avoid
Consider prophylactic anti-emetic medications as Clolar is moderately emetogenic.
Consider the use of prophylactic steroids to mitigate Systemic Inflammatory Response Syndrome (SIRS) or capillary leak syndrome (e.g., hypotension, tachycardia, tachypnea, and pulmonary edema).
Minimize exposure to drugs with known renal toxicity during the 5 days of Clolar administration since the risk of renal toxicity may be increased.
Consider avoiding concomitant use of medications known to induce hepatic toxicity.
2.3 Dose Modifications and Reinitiation of Therapy
Hematologic Toxicity
Administer subsequent cycles no sooner than 14 days from the starting day of the previous cycle and provided the patient's ANC is ≥ 0.75 × 109/L.
If a patient experiences a Grade 4 neutropenia (ANC <0.5 × 109/L) lasting ≥4 weeks, reduce dose by 25% for the next cycle.
Non-hematologic Toxicity
Withhold Clolar if a patient develops a clinically significant infection, until the infection is controlled, then restart at the full dose.
Withhold Clolar for a Grade 3 non-infectious non-hematologic toxicity (excluding transient elevations in serum transaminases and/or serum bilirubin and/or nausea/vomiting controlled by antiemetic therapy). Re-institute Clolar administration at a 25% dose reduction when resolution or return to baseline.
Discontinue Clolar administration for a Grade 4 non-infectious non-hematologic toxicity.
Discontinue Clolar administration if a patient shows early signs or symptoms of SIRS or capillary leak (e.g., hypotension, tachycardia, tachypnea, and pulmonary edema) occur and provide appropriate supportive measures.
Discontinue Clolar administration if Grade 3 or higher increases in creatinine or bilirubin are noted. Re-institute Clolar with a 25% dose reduction, when the patient is stable and organ function has returned to baseline. If hyperuricemia is anticipated (tumor lysis), initiate measures to control uric acid.
2.4 Reconstitution/Preparation
Clolar should be filtered through a sterile 0.2 micron syringe filter and then diluted with 5% Dextrose Injection, USP, or 0.9% Sodium Chloride Injection, USP, prior to intravenous (IV) infusion to a final concentration between 0.15 mg/mL and 0.4 mg/mL. Use within 24 hours of preparation. Store diluted Clolar at room temperature (15–30ºC).
2.5 Incompatibilities
Do not administer any other medications through the same intravenous line.
