Uses of Darboren: - Anemia due to chronic kidney disease - Anemia due to cancer chemotherapy Anaemia of chronic renal failure, Anaemia in chemotherapy patients Hypersensitivity, uncontrolled hypertension.

Haematopoietic Agents

Darbepoetin alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Erythropoietin interacts with progenitor stem cells to increase red cell production. Binding of erythropoietin to the erythropoietin receptor leads to receptor dimerization, which facilitates activation of JAK-STAT signaling pathways within the cytosol. Activated STAT (signal transducers and activators of transcription) proteins are then translocated to the nucleus where they serve as transcription factors which regulate the activation of specific genes involved in cell division or differentiation.

How to use Darbepoetin alfa: Your doctor or nurse will give you this medicine. Kindly do not self administer. Adult Dose: Chronic Kidney Disease-Associated Anemia CKD not on dialysis Recommended starting dose: 0.45 mcg/kg IV/SC q4weeks Consider initiating ESA treatment only when the hemoglobin level is <10 g/dL If the hemoglobin level exceeds 10 g/dL, reduce or interrupt ESA dose and use the lowest dose sufficient to reduce the need for red blood cell transfusions CKD on dialysis Initiate ESA treatment when the hemoglobin level is <10 g/dL If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA Recommended starting dose: 0.45 mcg/kg IV or SC qWeek or 0.75 mcg/kg q2weeks; the IV route is recommended for patietns on hemodialysis Intravenous route recommended for patients on hemodialysis Chemotherapy-Related Anemia with Nonmyeloid Malignancies 2.25 mcg/kg SC qWeek OR 500 mcg SC q3Weeks If Hgb increases <1 g/dL after 6 weeks, may increase dose no more than 4.5 mcg/kg Reduce dose by 40% if rapid increase in Hgb (eg, >1 g/dL in 2-week period) Discontinue if no response after 8 weeks Child Dose: Chronic Kidney Disease-Associated Anemia Initiate treatment when the hemoglobin level is <10 g/dL If the hemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose Recommended starting dose for pediatric patients (<18 yr) is 0.45 mcg/kg SC or IV qWeek Patients not receiving dialysis may also be initiated at a dose of 0.75 mcg/kg q2Week Chemotherapy-related Anemia Safety and efficacy not established Renal Dose: Chronic Kidney Disease-Associated Anemia CKD not on dialysis Recommended starting dose: 0.45 mcg/kg IV/SC q4weeks Consider initiating ESA treatment only when the hemoglobin level is <10 g/dL If the hemoglobin level exceeds 10 g/dL, reduce or interrupt ESA dose and use the lowest dose sufficient to reduce the need for red blood cell transfusions CKD on dialysis Initiate ESA treatment when the hemoglobin level is <10 g/dL If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA Recommended starting dose: 0.45 mcg/kg IV or SC qWeek or 0.75 mcg/kg q2weeks; the IV route is recommended for patietns on hemodialysis Intravenous route recommended for patients on hemodialysis

Antagonism of hypotensive effect and increased risk of hyperkalemia with ACE inhibitors and angiotensin II receptor antagonists. Ethanol.

Hypersensitivity, uncontrolled hypertension.

Common - High blood pressure - Hypersensitivity >10% Cancer patients Fatigue (33%),Diarrhea (22%),Edema (21%),Fever (19%),Dizziness (14%),Arthralgia (13%),Headache (12%),Death (10%) Chronic renal failure patients Infectious disease (24%),Hyper/Hypotension (20%),Spasm (17%),Upper respiratory infection, Headache (15%),Diarrhea, Vomiting (14%),Nausea (11%),Peripheral edema, Dyspnea (10%),Abdominal pain (10%) 1-10% Cancer patients Myalgia (8%),Hypertension (3.7%),Pneumonia (3%),Dyspnea (2%),Vomiting (2%),Pulmonary embolism (1.3%) Chronic renal failure patients Arthralgia, Cough, Fatigue (9%),Limb pain (8%),Dizziness, Fever (7%),Death (6%),Edema (6%),Anemia, DVT, red cell aplasia (5.6%),Cardiac arrest, Cardiac dysrhythmia, Congestive heart failure (5%),Myocardial infarction, CVA(2%) <1% Cancer patients Hypertensive encephalopathy (0.6%),Seizure (0.6%),Chronic renal failure patients,Hypertensive encephalopathy (<1%),Seizure (<1%),Transient ischemic attack (<1% ) Frequency Not Defined Tumor progression,Venous thromboembolism,Immune hypersensitivity reaction (rare ),Injection site thrombosis

Pregnancy Category C. It is not known whether Darbepoetin Alfa is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Darbepoetin Alfa is administered to a nursing woman.

Precaution: Hypertension; history of seizures; hepatic impairment; sickle cell anaemia; sudden stabing migraine-like pain (warning sign of hypotensive crisis); exclude other causes of anaemia; ischaemic vascular disease; thrombocytosis; epilepsy; malignant disease; increase in heparin dose may be needed; increased risk of thrombosis when used for anaemia before orthopedic surgery; CV disease including recent MI/cerebrovascular accident. Monitor haemoglobin, BP and electrolytes; platelet count for 1st 8 wk. Lactation: not known if excreted in breast milk, use caution

Darbepoetin overdosage can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of Darbepoetin dosage and/or with phlebotomy, as clinically indicated. Cases of severe hypertension have been observed following overdose with ESAs

Store at 2°C to 8°C. Do not freeze. Do not shake. Protect from light; store Darbepoetin Alfa in the carton until use. Do not use Darbepoetin Alfa that has been shaken or frozen.

Haematopoietic Agents

Darbepoetin alfa is a biosynthetic form of erythropoietin. Recombinant human erythropoietin with sialic acid additions to enhance stability; stimulates erythropoiesis via division & differentation of progenitor cells in bone marrow to induce the release of reticulocytes from the bone marrow into the bloodstream to become erythrocytes.

Pregnancy Limited available data on pregnant women are insufficient to determine a drug-associated risk of major birth defects or miscarriage; in animal reproductive and developmental toxicity studies, drug increased early post-implantation loss at doses approximating clinical recommended starting doses; consider benefits and risks for the mother and possible risks to fetus when prescribing to a pregnant woman Lactation There is no information regarding presence of drug in human milk, effects on breastfed child, or on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition