Evoltra Concentrate Solution for Infusion 1mg/ml

SANOFI-AVENTIS SINGAPORE PTE. LTD.

SANOFI-AVENTIS SINGAPORE PTE. LTD.

Therapeutic

Prescription Only

SOLUTION, CONCENTRATE

**Posology and method of administration** Therapy must be initiated and supervised by a physician experienced in the management of patients with acute leukaemias. Posology _Adults (including the elderly)_ There are currently insufficient data to establish the safety and efficacy of clofarabine in adult patients (see section _Pharmacokinetic properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Paediatric patients_ _Children and adolescents (≥ 1 year old)_ The recommended dose in monotherapy is 52 mg/m2 of body surface area administered by intravenous infusion over 2 hours daily for 5 consecutive days. Body surface area must be calculated using the actual height and weight of the patient before the start of each cycle. Treatment cycles should be repeated every 2 to 6 weeks (from the starting day of the previous cycle) following recovery of normal haematopoiesis (i.e., ANC ≥ 0.75 × 109/l) and return to baseline organ function. A 25% dose reduction may be warranted in patients experiencing significant toxicities (see below). There is currently limited experience of patients receiving more than 3 treatment cycles (see section _Special warnings and precautions for use_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). The majority of patients who respond to clofarabine achieve a response after 1 or 2 treatment cycles (see section _Pharmacodynamic properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Therefore, the potential benefit and risks associated with continued therapy in patients who do not show haematological and/or clinical improvement after 2 treatment cycles should be assessed by the treating physician (see section _Special warnings and precautions for use_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Children (weighing < 20 kg):_ An infusion time of > 2 hours should be considered to help reduce symptoms of anxiety and irritability, and to avoid unduly high maximum concentrations of clofarabine (see section _Pharmacokinetic properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Children (< 1 year old):_ There are no data on the pharmacokinetics, safety or efficacy of clofarabine in infants. Therefore, a safe and effective dosage recommendation for patients (< 1 year old) has yet to be established. _Dose reduction for patients experiencing haematological toxicities_ If the ANC does not recover by 6 weeks from the start of a treatment cycle, a bone marrow aspirate / biopsy should be performed to determine possible refractory disease. If persistent leukaemia is not evident, it is recommended that the dose for the next cycle be reduced by 25% of the previous dose following recovery of ANC to ≥ 0.75 × 109/l. Should patients experience an ANC < 0.5 × 109/l for more than 4 weeks from the start of the last cycle, it is recommended that the dose for the next cycle be reduced by 25%. _Dose reduction for patients experiencing non-haematological toxicities Infectious events_ If a patient develops a clinically significant infection, clofarabine treatment may be withheld until the infection is clinically controlled. At this time, treatment may be reinitiated at the full dose. In the event of a second clinically significant infection, clofarabine treatment should be withheld until the infection is clinically controlled and may be reinitiated at a 25% dose reduction. _Non-infectious events_ If a patient experiences one or more severe toxicities (US National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 3 toxicities excluding nausea and vomiting), treatment should be delayed until the toxicities resolve to baseline parameters or to the point where they are no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation. It is then recommended that clofarabine be administered at a 25% dose reduction. Should a patient experience the same severe toxicity on a second occasion, treatment should be delayed until the toxicity resolves to baseline parameters or to the point where it is no longer severe and the potential benefit of continued treatment with clofarabine outweighs the risk of such continuation. It is then recommended that clofarabine be administered at a further 25% dose reduction. Any patient who experiences a severe toxicity on a third occasion, a severe toxicity that does not recover within 14 days (see above for exclusions), or a life-threatening or disabling toxicity (US NCI CTC Grade 4 toxicity) should be withdrawn from treatment with clofarabine (see section _Special warnings and precautions for use_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Special populations_ _Renal impairment_ The limited data available indicate that clofarabine may accumulate in patients with decreased creatinine clearance (see sections _Special warnings and precautions for use_ and _Pharmacokinetic properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Clofarabine is contraindicated in patients with severe renal insufficiency (see section _Contraindications_) and should be used with caution in patients with mild to moderate renal insufficiency (see section _Special warnings and precautions for use_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Patients with moderate renal impairment (creatinine clearance 30 – <60 ml/min) require a 50% dose reduction (see section _Pharmacokinetic properties_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Hepatic impairment:_ There is no experience in patients with hepatic impairment (serum bilirubin > 1.5 x ULN plus AST and ALT > 5 x ULN) and the liver is a potential target organ for toxicity. Therefore, clofarabine is contraindicated in patients with severe hepatic impairment (see section _Contraindications_) and should be used with caution in patients with mild to moderate hepatic impairment (see section _Special warnings and precautions for use_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Method of administration The recommended dosage should be administered by intravenous infusion although it has been administered via a central venous catheter in clinical trials. Evoltra® must not be mixed with or concomitantly administered using the same intravenous line as other medicinal products (see section _Incompatibilities_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). For instructions on filtration and dilution of the medicinal product before administration, see section _Special precautions for disposal and other handling_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_.