Usual Adult Dose for Anemia Associated with Chronic Renal Failure

For use in dialysis patients only.

0.04 mg/kg administered as a single intravenous or subcutaneous injection once monthly.

Renal Dose Adjustments

Peginesatide is not indicated and is not recommended in patients with renal dysfunction who are not on dialysis.

Liver Dose Adjustments

Data not available.

Dose Adjustments

Individualize dosing and use the lowest dose of peginesatide that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions.

If the hemoglobin rises rapidly (more than 1 g/dL in the 2 weeks prior to the dose or more than 2 g/dL in 4 weeks), reduce the dose of peginesatide by 25% or more as needed to reduce rapid responses.

If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of peginesatide. After a dose has been withheld and once the hemoglobin begins to decrease, peginesatide may be restarted at a dose approximately 25% below the previously administered dose.

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%.

Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks until the hemoglobin is stable and sufficient to minimize the need for RBC transfusion. Thereafter, hemoglobin should be monitored at least monthly provided hemoglobin levels remain stable.

For patients who do not respond adequately over a 12 week escalation period, increasing the peginesatide dose further is unlikely to improve response and may increase risks. Evaluate other causes of anemia. Discontinue peginesatide if responsiveness does not improve.

In patients previously receiving epoetin alfa or darbepoetin alfa, estimate the starting monthly dose of peginesatide based on the weekly dose of epoetin alfa or darbepoetin alfa at the time of substitution, maintaining the route of administration (either intravenous or subcutaneous):

For epoetin alfa (EA) dose of less than 2500 units/week or darbepoetin alfa (DA) dose of less than 12 mcg/week, initiate peginesatide at 2 mg/month.
For EA dose of 2500 to less than 4300 units/week or DA dose of 12 to less than 18 mcg/week, begin peginesatide at 3 mg/month.
For EA dose of 4300 to less than 6500 or DA dose of 18 to less than 25, begin peginesatide at 4 mg/month.
For EA dose of 6500 to less than 8900 units/week or DA dose of 25 to less than 35 mcg/week, begin peginesatide at 5 mg/month.
For EA dose of 8900 to less than 13,000 units/week or DA dose of 35 to less than 45 mcg/week, begin peginesatide at 6 mg/month.
For EA dose of 13,000 to less than 19,000 units/week or DA dose of 45 to less than 60 mcg/week, begin peginesatide at 8 mg/month.
For EA dose of 19,000 to less than 33,000 units/week or DA dose of 60 to less than 95 mcg/week, begin peginesatide at 10 mg/month.
For EA dose of 33,000 to less than 68,000 units/week or DA dose of 95 to less than 175 mcg/week, begin peginesatide at 15 mg/month.
For EA dose of greater than or equal to 68,000 units/week or DA dose of greater than or equal to 175 mcg/week, begin peginesatide at 20 mg/month.

The first dose of peginesatide should be administered one week after the last epoetin alfa dose was administered or at the next scheduled dose in place of darbepoetin alfa.

Precautions

Evaluate the iron status in all patients before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia (vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating peginesatide. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%.

Initiate peginesatide treatment only when the hemoglobin level is less than 10 g/dL.

Following initiation of therapy and after each dose adjustment, monitor hemoglobin every 2 weeks until the hemoglobin is stable and sufficient to minimize the need for RBC transfusion. Thereafter, hemoglobin should be monitored at least monthly provided hemoglobin levels remain stable.

Appropriately control hypertension prior to initiation of and during treatment with peginesatide. Reduce or withhold peginesatide if blood pressure becomes difficult to control.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

See dosing section above.

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for peginesatide. It includes a communication plan. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

If a dose of peginesatide is missed, administer the missed dose as soon as possible and restart peginesatide at the prescribed once monthly dosing frequency.

Peginesatide should be stored refrigerated at 36 degrees to 46 degrees Fahrenheit (2 to 8 degrees Celsius). Protect from light. Retain in carton until time of use.

Use the single use vial or single use prefilled syringe only one time and discard any unused portion.

Store unused portions of peginesatide in multiple use vials at 36 degrees to 46 degrees Fahrenheit (2 to 8 degrees Celsius). Discard 28 days after first use.
Do not use if the tamper evident seal on the carton is broken or missing.
Do not dilute peginesatide and do not administer in conjunction with other drug solutions.

Peginesatide should be inspected visually for particulate matter and coloration prior to administration. Do not use any vials or prefilled syringes of peginesatide exhibiting particulate matter or a coloration other than colorless to slightly yellow.