Prescribing Details
Description
DARBAGENT® is a preparation of Darbepoetin Alfa which is an erythropoiesis stimulating protein that is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. Darbepoetin Alfa is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains. The 2 additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone. Darbepoetin Alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.
Uses
No Data
Indications
DARBAGENT® is an erythropoiesis stimulating agent (ESA) indicated for the treatment of anemia due to:
• Chronic kidney disease (CKD) in patients on dialysis and patients not on dialysis.
• The effects of concomitant myelosuppressive chemotherapy and upon initiation, there is a minimum of two additional months of planned chemotherapy.
Dosage and administration
Route of administration: DARBAGENT® should be taken by parenteral (intravenous or subcutaneous) route.
Patients with chronic kidney disease (CKD)
For all patients with CKD
When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.
• Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
• If the hemoglobin rises rapidly (e.g., more than 1 g/dl in any 2 week period), reduce the dose of DARBAGENT® by 25% or more as needed to reduce rapid responses.
• For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dl after 4 weeks of therapy, increase the dose by 25%.
• For patients who do not respond adequately over a 12 week escalation period, increasing the DARBAGEN dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue DARBAGEN® if responsiveness does not improve.
For adult patients with CKD on dialysis
• Initiate DARBAGENT® treatment when the hemoglobin level is less than 10 g/dl.
• If the hemoglobin level approaches or exceeds 11 g/dl, reduce or interrupt the dose of DARBAGENT®.
• The recommended starting dose is 0.45 mcg/kg intravenously or subcutaneously as a weekly injection or 0.75 mcg/kg once every 2 weeks as appropriate. The intravenous route is recommended for patients on hemodialysis.
For adult patients with CKD not on dialysis
• Consider initiating DARBAGENT® treatment only when the hemoglobin level is less than 10 g/dl and the following apply:
-The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and
- Reducing the risk of alloimmunization and/or other RBC transfusion related risks is a goal
• If the hemoglobin level exceeds 10 g/dl, reduce or interrupt the dose of DARBAGENT® and use the lowest dose of DARBAGENT® sufficient to reduce the need for RBC transfusions.
• The recommended starting dose is 0.45 mcg/kg body weight intravenously or subcutaneously given once at four week intervals as appropriate.
For pediatric patients with CKD
• Initiate DARBAGENT® treatment when the hemoglobin level is less than 10 g/dl.
• If the hemoglobin level approaches or exceeds 12 g/dl, reduce or interrupt the dose of DARBAGENT®.
• The recommended starting dose for pediatric patients (less than 18 years) is 0.45 mcg/kg body weight administered as a single subcutaneous or intravenous injection once weekly: patients not receiving dialysis may also be initiated at a dose of 0.75 mcg/kg once every 2 weeks.
Conversion from epoetin alfa to DARBAGENⓇ in patients with CKD on dialysis
DARBAGENT® is administered less frequently than epoetin alfa.
• Administer DARBAGENT® once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly.
•Administer DARBAGENT® once every 2 weeks in patients who were receiving epoetin alfa once weekly.
Estimate the starting weekly dose of DARBAGENT® for adults and pediatric patients on the basis of the weekly epoetin alfa dose at the time of substitution. Maintain the route of administration (intravenous or subcutaneous injection).
| Estimated DARBAGENT® starting doses (mcg/week) for patients with CKD on dialysis based on previous epoetin alfa dose (units/week) | ||
|---|---|---|
| Previous weekly epoetin alfa dose (units/week) | DARBAGENT® dose (mcg/week) | |
| Adult | Pediatric | |
| <1,500 | 6.25 | * |
| 1,500 to 2,499 | 6.25 | 6.25 |
| 2,500 to 4,999 | 12.5 | 10 |
| 5,000 to 10,999 | 25 | 20 |
| 11,000 to 17,999 | 60 | 60 |
| 34,000 to 89,999 | 100 | 100 |
| ≥ 90,000 | 200 | 200 |
*For pediatric patients receiving a weekly epoetin alfa dose of 1,500 units/week, the available data are insufficient to determine a DARBAGENT® conversion dose.
Conversion from epoetin alfa to DARBAGENT® in patients with CKD not on dialysis The dose conversion depicted in above table does not accurately estimate the once monthly dose of DARBAGENT®.
Patients on cancer chemotherapy
Initiate DARBAGENT® in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dl, and if there is a minimum of two additional months of planned chemotherapy. Use the lowest dose of DARBAGENⓇ necessary to avoid RBC transfusions. The recommended starting dose and schedules are:
• 2.25 mcg/kg every week subcutaneously until completion of a chemotherapy course
• 500 mcg every 3 weeks subcutaneously until completion of a chemotherapy course
| Dose adjustment | Weekly Schedule | Every 3 week schedule |
|---|---|---|
| •If hemoglobin increases greater than 1 g/dl in any 2 week period or If hemoglobin reaches a level needed to avoid RBC transfusion • If hemoglobin exceeds a level needed to avoid RBC transfusion |
Reduce dose by 40% | Reduce dose by 40% |
| If hemoglonin exceeds a level needed to avoid RBC transfusion | • Withhold dose until hemoglobin approaches a level where RBC transfusions may be required • Reinitiate at a dose 40% below the previous dose |
• Withhold dose until hemoglobin approaches a level where RBC transfusions may be required • Reinitiate at a dose 40% below the previous dose |
| If hemoglobin increases by less than 1 g/dl and remains below 10 g/dl after 6 weeks of therapy | Increase dose to 4.5 mcg/kg/week | No dose adjustment |
| • If there is no response as measured by hemoglobin levels or if RBC transfusions are still required after 8 weeks of therapy • Following completion of a chemotherapy course |
Discontinue DARBAGENT® | Discontinue DARBAGENT® |
Limitations of use
DARBAGENT® has not been shown to improve quality of life, fatigue, or patient well-being. DARBAGENT® is not indicated for use-
• In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
• In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
• In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.
• As a substitute for RBC transfusions in patients who require immediate correction of anemia.
Use in pregnancy & lactation
Pregnancy: The limited available data on darbepoetin alla use in pregnant women are insufficient to determine a drug-associated risk of major birth defects or miscarriage. Consider the benefits and risks of darbepoetin alfa for the mother and possible risks to the fetus when prescribing it to a pregnant woman,
Lactation: There is no information regarding the presence of darbepoetin alfa in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk, caution should be exercised when darbepoetin alfa is administered to a nursing woman.
Use in children and adolescents
The safety and effectiveness of darbepoetin alfa in pediatric patients with CKD receiving and not receiving dialysis have not been established less than 1 month old. The safety and efficacy of darbepoetin alfa in pediatric patients with cancer have not been established.
Precautions
Using darbepoetin alfa to target a hemoglobin level of greater than 11 g/dl increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in patients with coexistent cardiovascular disease and stroke. It also increased mortality or increased risk of tumor progression or recurrence in patients with cancer. Hypertension should be controlled prior to initiating and during treatment with darbepoetin alfa. Darbepoetin alfa increases the risk for seizures in patients with CKD, so caution should be exercised during the use of this medication. If severe anemia and low reticulocyte count develop during darbepoetin alfa treatment, withhold darbepoetin alfa and evaluate for PRCA.
Side effects
The most common side effects of darbepoetin alfa-treated patients with CKD are hypertension, dyspnea, peripheral edema, cough and procedural hypotension.
The most common side effects of darbepoetin alfa-treated patients with cancer receiving chemotherapy are abdominal pain, edema and thrombovascular events.
Contraindications
Darbepoetin alfa is contraindicated in patients with known hypersensitivity to darbepoetin alfa or any other components of this product. It is also contraindicated in patients with uncontrolled hypertension and pure red cell aplasia (PRCA) that begins after treatment with darbepoetin alfa or other erythropoietin protein drugs.
Drug interactions
Drug interaction with medication: The clinical results obtained so far do not indicate any interaction of darbepoetin alfa with other substances. However, there is potential for an interaction with substances that are highly bound to red blood cells e.g., cyclosporine, tacrolimus. If darbepoetin alfa is given concomitantly with any of these treatments, blood levels of these substances should be monitored and dosage adjusted as the hemoglobin rises.
Drug interaction with food and others: Not applicable.
Overdose
Darbepoetin alfa overdosage can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of darbepoetin alfa dosage or with phlebotomy, as clinically indicated. Cases of severe hypertension have been observed following overdose with ESAS.
Preparation
• The needle cover of the pre-filled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions.
• Do not shake. Do not use DARBAGEN® that has been shaken or frozen.
Protect pre-filled syringes from light.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any pre-filled syringes exhibiting particulate matter or discoloration.
• Discard unused portion of DARBAGEN® in pre-filled syringes.
• Do not dilute DARBAGEN® and do not administer in conjunction with other drug solutions.
Pharmaceutical precautions
Store in a refrigerator at 2°C to 8°C, protected from light. Do not shake and do not keep in deep fridge. Keep away from the reach of children. To be taken and sold only on the prescription of a registered physician.
Presentation
DARBAGENT® 40 IV /SC injection: Each pre-filled syringe contains 0.4ml sterile solution of Darbepoetin Alfa INN 40 mcg.
DARBAGENT® 60 IV /SC injection: Each pre-filled syringe contains 0.3 ml sterile solution of Darbepoetin Alfa INN 60 mcg.
DARBAGENT® 100 IV/SC injection: Each pre-filled syringe contains 0.5 ml sterile solution of Darbepoetin Alfa INN 100 mcg.
Package quantities
DARBAGENT® 40 IV/SC injection: Each box contains 1 pre-filled syringe with a needle and needle cap containing 0.4 ml sterile solution of Darbepoetin Alfa INN 40 mcg, a first aid bandage and an alcohol pad.
DARBAGENT® 60 IV/SC injection: Each box contains 1 pre-filled syringe with a needle and needle cap containing 0.3 ml sterile solution of Darbepoetin Alfa INN 60 mcg, a first aid bandage and an alcohol pad.
DARBAGENT® 100 IV/SC injection: Each box contains 1 pre-filled syringe with a needle and needle cap containing 0.5 ml sterile solution of Darbepoetin Alfa INN 100 mcg, a first aid bandage and an alcohol pad.
