peginesatide

Action

Binds to and activates human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro; increases reticulocyte count, followed by increases in hemoglobin. Rate of hemoglobin increase varies among patients and is dependent on peginesatide dosage.

Availability

Solution for injection: 2 mg/0.5 ml, 3 mg/0.5 ml, 4 mg/0.5 ml, 5 mg/0.5 ml, 6 mg/0.5 ml in single-use vials; 1 mg/0.5 ml, 2 mg/0.5 ml, 3 mg/0.5 ml, 4 mg/0.5 ml, 5 mg/0.5 ml, 6 mg/0.5 ml in prefilled syringes; 10 mg/ml, 20 mg/2 ml in multi-use vials

Indications and dosages

➣ Anemia caused by chronic kidney disease in patients on dialysis

Adults: Initially when hemoglobin level is less than 10 g/dl, 0.4 mg/kg subcutaneously or I.V. once monthly. When converting from another ESA, give once monthly based on total weekly epoetin or darbepoetin alfa dose at time of conversion.

Dosage adjustment

• Based on hemoglobin level

Contraindications

• Uncontrolled hypertension

Precautions

Use cautiously in:

• patients with chronic kidney disease and an insufficient hemoglobin response

• patients with chronic kidney disease not on dialysis

• coexistent CV disease and stroke, controlled hypertension

• anemia due to cancer chemotherapy (not indicated)

• patients undergoing coronary artery bypass graft surgery or orthopedic procedures

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Don't dilute drug or administer with other drug solutions.

• Evaluate transferrin saturation and serum ferritin level before starting drug; administer supplemental iron therapy when serum ferritin level is less than 100 mcg/L or when serum transferrin saturation is less than 20%, as prescribed. Be aware that other causes of anemia (such as vitamin deficiency, metabolic or chronic inflammatory conditions, or bleeding) should be corrected or excluded before initiating drug.

• Monitor hemoglobin level at least every 2 weeks until stable. When adjusting therapy, consider hemoglobin rate of rise, rate of decline, ESA responsiveness, and hemoglobin variability; be aware that a single hemoglobin excursion may not require a dosing change. Don't increase dosage more frequently than once every 4 weeks.

See Be aware that for patient who doesn't respond adequately over a 12-week escalation period, increasing dosage further is unlikely to improve response and may increase risks. Drug should be used at the lowest dosage that will maintain a hemoglobin level sufficient to reduce need for RBC transfusions. Discontinue drug if responsiveness doesn't improve.

See Be aware that using ESAs to target a hemoglobin level greater than 11 g/dl increases risk of serious adverse CV reactions and hasn't been shown to provide additional benefits. Ensure that patient's hypertension is under control before starting treatment. Reduce dosage or withhold drug if blood pressure becomes difficult to control.

See Be aware that patients with cancer receiving ESAs or patients undergoing coronary artery bypass graft surgery may be at increased risk for serious CV adverse reactions or death; patients undergoing orthopedic procedures may be at risk for deep vein thrombosis; and patients with chronic kidney disease not on dialysis may be at increased risk for CV events.

• Be aware that the presence of peginesatide-specific binding antibodies is associated with declining hemoglobin levels and may require increased drug dosages to maintain hemoglobin levels or transfusion for anemia of chronic kidney disease.

See Discontinue drug and administer appropriate therapy if a serious allergic reaction occurs.

Adverse reactions

CNS: headache, seizures, stroke

CV: procedural hypotension, hypotension, hypertension, congestive heart failure (CHF), myocardial infarction (MI)

GI: nausea, vomiting, diarrhea

Hematologic: thromboembolism

Metabolic: hyperkalemia

Musculoskeletal: muscle spasms, extremity pain, back pain, arthralgia

Respiratory: dyspnea, cough, upper respiratory tract infection

Other: arteriovenous fistula-site complications, pyrexia, peginesatide-specific binding antibodies, allergic reactions, increased mortality

Interactions

Drug-diagnostic tests. Potassium: increased level

Patient monitoring

• Continue to monitor hemoglobin level at least monthly provided hemoglobin level remains stable.

• Continue to evaluate transferrin saturation and serum ferritin level during treatment and to administer supplemental iron as prescribed.

See During first several months after drug initiation, closely monitor patient for neurologic symptoms; appropriately control hypertension; and watch for such CV events as stroke, MI, and CHF.

• Be aware that patient receiving peginesatide may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.

Patient teaching

• If patient will self-administer drug, tell him to follow exact directions for injection, storage, and proper disposal of needles and syringes.

See Advise patient to immediately report allergic reactions; new-onset seizures, premonitory symptoms, or change in seizure frequency; and CV signs and symptoms.

• Advise patient of importance of having blood tests and blood pressure checks, and of compliance with antihy-pertensive therapy, iron supplements, and dietary restrictions.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.