NESP INJECTION PLASTIC SYRINGE 40 μg/0.5 ml

KYOWA KIRIN ASIA PACIFIC PTE. LTD.

KYOWA KIRIN ASIA PACIFIC PTE. LTD.

Therapeutic

Prescription Only

INJECTION, SOLUTION, CONCENTRATE

**DOSAGE AND ADMINISTRATION** **For CRF Patients and Patients with Non-Myeloid Malignancies Receiving Chemotherapy** Use the lowest dose of NESP® that will gradually increase the haemoglobin concentration to approach a target of not more than 12 g/dL; the rate of haemoglobin increase should not exceed 1 g/dL in any 2-week period. Rapid increases in haemoglobin concentrations or the use of erythropoietins in subjects with normal haemoglobin concentrations, may result in an increased risk of thrombotic adverse events (see **PRECAUTIONS-Cardiovascular and Thrombotic Events/Increased Mortality** – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **CRF Patients** NESP® can be administered either SC or IV. The dose should be started and titrated slowly (e.g. once every 4 weeks) based on individual haemoglobin levels. The haemoglobin target, regardless of the treatment population should not exceed 12 g/dL (see **Dose Adjustment in CRF patients**). Clinical studies have shown interpatient response to be variable. If a patient fails to respond or maintain a response, other aetiologies should be considered and evaluated (see **PRECAUTIONS: General** – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Haemoglobin levels should be monitored frequently until stable. Thereafter, haemoglobin levels can be monitored less frequently. In clinical studies that were used for approval of darbepoetin alfa in patients with chronic renal failure, haemoglobin levels were measured every 1 to 2 weeks. Dosing instructions are provided for two phases treatment: correction of anaemia and maintenance of the target haemoglobin level. Instructions for dose adjustment and for conversion from recombinant human erythropoietin (r-HuEPO) to NESP® are also provided. **Correction of Anaemia** The initial NESP® dosage by SC or IV administration is 0.45 mcg/kg body weight, as a single injection once weekly. If the increase in haemoglobin is inadequate (less than 1 g/dL in 4 weeks) and iron stores are adequate (see **PRECAUTIONS: General** – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_), the dose of NESP® may be increased by approximately 25%. Further increases may be made at 4-week intervals, until the desired response is attained. **Maintenance of Haemoglobin Concentration** In patients on dialysis and not on dialysis, NESP® may be dosed weekly or once every 2 weeks at the titrated dose to maintain he target haemoglobin. If a dose adjustment is required to maintain a target haemoglobin, the individual dose may be adjusted at 4-week intervals until the appropriate haemoglobin level is achieved (see **Dose Adjustment in CRF Patients**). After any dose adjustment the haemoglobin should be monitored every 1 to 2 weeks until stable and less frequently thereafter. Dose changes in the maintenance phase of treatment should not be made more frequently than every 2 weeks. When changing the route of administration, the same dose should be used and the haemoglobin monitored so that the appropriate NESP® dose adjustments can be made to keep the haemoglobin at a target not to exceed 12 g/dL. Data from 809 patients receiving darbepoetin alfa in Australian and European clinical studies were analysed to assess the dose required to maintain haemoglobin; no difference was observed between the average weekly dose administered via the IV and SC routes of injection. **Dose Adjustment in CRF Patients** The dose should be adjusted for each patient to achieve and maintain a target haemoglobin not to exceed 12 g/dL. Dose adjustment instructions should be followed to achieve and maintain a target haemoglobin or in response to an excessive rate of rise of haemoglobin. If the haemoglobin is increasing and approaching 12 g/dL, the dose should be reduced by approximately 25%. If after a dose reduction, haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point, therapy should be reinstated at a dose approximately 25% below the previous dose. If the rise in haemoglobin is more than 1 g/dL in 2 weeks, reduce the dose by 25%. Haemoglobin levels should be monitored every 1 to 2 weeks until stable and less frequently thereafter. **Conversion from Recombinant Human Erythropoietin to NESP** ® Due to its longer serum half-life, NESP® can be administered less frequently than r-HuEPO. Clinical experience has shown that patients receiving r-HuEPO 2 or 3 times weekly may change to once weekly NESP®. Those receiving r-HuEPO once weekly may change to NESP® administered once every 2 weeks. The substitution of NESP® for r-HuEPO should be based on the patient's r-HuEPO dose at the time of substitution, and the same route of administration should be used. The initial SC dose of NESP® (mcg/week) can be determined by dividing the total weekly SC dose of r-HuEPO (units/week) by 200, while the initial IV dose can be determined by dividing the total weekly IV dose of r-HuEPO (units/week) by 240. Because of individual variability, doses should be titrated as described above to maintain the haemoglobin at the desired concentration. **Patients with Non-Myeloid Malignancy Receiving Chemotherapy** Treatment should not be commenced unless haemoglobin falls below 10–11 g/dL. The recommended initial dose is 2.25 mcg/kg given once weekly as a single SC injection. The aim of treatment is to increase haemoglobin concentration to a target no to exceed 12 g/dL and to reduce the requirement for blood transfusions. The therapy should be continued for approximately 4 weeks after the end of chemotherapy or until haemoglobin concentrations approach 12 g/dL. **Dose Adjustment-Cancer Patients** If the haemoglobin approaches 12 g/dL, the dose should be reduced by approximately 25% to 50%. If the haemoglobin exceeds 12 g/dL, doses should be temporarily withheld until the haemoglobin decreases to approximately 11 g/dL, at which point therapy should be re-initiated at 25% to 50% below the previous dose. For patients receiving darbepoetin alfa on a weekly basis the increase in haemoglobin is inadequate (less than 1 g/dL after approximately 1 month of therapy) or if the response is not satisfactory in terms of reducing red blood cell transfusion requirements, the dose should be doubled to 4.5 mcg/kg given once weekly. **Anaemia with Myelodysplastic Syndrome** The usual dose of NESP in adults is 240 mcg as darbepoetin alfa (genetical recombination), to be administered as a single subcutaneous injection once weekly. The dose should be decreased in view of the degree of anaemic, symptoms and the patient's age. The efficacy and safety of NESP in combination with other antitumour agents have not been established. If cases such as excessive haemopoiesis occur (the haemoglobin concentration exceeds approximately 11 g/dL) and dose reduction is required, the dose should be reduced by approximately 50%. If after dose reduction, the haemoglobin concentration falls (below approximately 9 g/dL) and dose increase is required, the dose should be increased approximately twofold. The dose should not exceed 240 mcg as a single injection. If the desired improvement in anaemia is not obtained or anaemia is aggravated after administration of NESP, change to another treatment should be considered. The necessity of continued administration of NESP should be assessed at approximately 16 weeks after the initiation of administration. (See CLINICAL TRIAL – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **Preparation and Administration of NESP** ® Do not takeout the syringe from its pillow package before administration. Before using NESP® Syringe, remove the Tip Cap. Attach an appropriate needle, etc., if necessary, and then administer the drug. Do not shake NESP®. Prolonged vigorous shaking may denature any protein, rendering it biologically inactive. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Do not use any products exhibiting particulate matter or discolouration. Do not dilute or administer NESP® in conjunction with other drug solutions. NESP® contains no antimicrobial agent. NESP® is for single use in one patient only. Discard any residue.