What is the recommended treatment and dosage for Parsabiv (etelcalcetide) in patients with secondary hyperparathyroidism and chronic kidney disease (CKD) on hemodialysis?

Parsabiv (Etelcalcetide) for Secondary Hyperparathyroidism in Hemodialysis Patients

Start etelcalcetide at 5 mg intravenously three times per week at the end of each hemodialysis session, ensuring corrected serum calcium is at or above the lower limit of normal before initiation. 1

Indication and Patient Selection

• Etelcalcetide is indicated specifically for adult patients with secondary hyperparathyroidism and chronic kidney disease on hemodialysis 1
• Do not use etelcalcetide in patients with parathyroid carcinoma, primary hyperparathyroidism, or CKD patients not on hemodialysis 1
• Etelcalcetide is a second-generation intravenous calcimimetic that binds directly to the calcium-sensing receptor to reduce PTH and calcium levels 2

Dosing Algorithm

Initial Dose:

• Begin with 5 mg IV bolus at the end of hemodialysis three times weekly 1
• Verify corrected serum calcium is at or above the lower limit of normal before starting therapy 1

Dose Titration:

• Increase dose in 2.5 mg or 5 mg increments when corrected serum calcium is within normal range and PTH remains above target, no more frequently than every 4 weeks 1
• Maximum dose is 15 mg three times weekly 1
• Minimum maintenance dose is 2.5 mg three times weekly 1
• Target PTH levels of 60-240 pg/mL while maintaining corrected serum calcium within normal range 3

Dose Reduction or Interruption:

• Decrease or temporarily discontinue if PTH falls below target range 1
• For corrected serum calcium between 7.5 mg/dL and lower limit of normal without symptoms: decrease dose or temporarily discontinue, or use concomitant therapies to increase calcium 1
• Stop etelcalcetide immediately if corrected serum calcium falls below 7.5 mg/dL or if symptomatic hypocalcemia occurs 1
• When restarting after hypocalcemia, resume at a dose 5 mg lower than the last administered dose (or 2.5 mg if last dose was 2.5 or 5 mg) 1

Monitoring Protocol

During Dose Initiation or Adjustment:

• Measure corrected serum calcium 1 week after any dose change 1
• Measure PTH 4 weeks after any dose change 1

During Maintenance:

• Measure corrected serum calcium every 4 weeks 1
• Measure PTH per clinical practice (typically every 3 months based on KDIGO recommendations) 4

Missed Doses

• If a hemodialysis session is missed, do not administer the missed etelcalcetide dose 1
• Resume at the next hemodialysis session at the prescribed dose 1
• If doses are missed for more than 2 weeks, re-initiate at 5 mg (or 2.5 mg if that was the patient's last dose) 1

Efficacy Data

• In a 52-week Japanese study, 87.5% of patients achieved target PTH levels (60-240 pg/mL) with etelcalcetide while maintaining control of serum calcium and phosphate 3
• Etelcalcetide demonstrates superior PTH reduction compared to oral cinacalcet 5
• Novel calcimimetics including etelcalcetide have similar or superior efficacy to cinacalcet for PTH reduction, though no survival benefits have been demonstrated with this drug class 6

Safety Profile and Common Pitfalls

Common Adverse Events:

• Nausea (4.7%), vomiting (9.5%), and symptomatic hypocalcemia (1.1%) were reported in clinical trials 3
• Most adverse events are mild to moderate, with 7.4% of patients discontinuing due to adverse events 3
• Gastrointestinal side effects are comparable to oral cinacalcet despite intravenous administration 5

Critical Safety Considerations:

• Hypocalcemia is the primary safety concern—always verify calcium is at or above lower limit of normal before starting or increasing dose 1
• Do not initiate vitamin D therapy until serum phosphorus is below 4.6 mg/dL to avoid worsening vascular calcification 4
• Avoid targeting normal PTH levels (<65 pg/mL) in dialysis patients, as this causes adynamic bone disease with increased fracture risk 4
• Monitor for symptoms of hypocalcemia (paresthesias, muscle cramps, tetany, seizures) even when calcium levels are within range 1

Comparative Considerations

• Intravenous administration three times weekly at dialysis improves adherence compared to daily oral cinacalcet 5
• Observational data suggest parathyroidectomy is associated with lower mortality than calcimimetics and shows more substantial increases in bone mineral density for severe refractory cases (PTH >800 pg/mL) 6, 7
• Consider parathyroidectomy when PTH persistently exceeds 800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 4