What is the recommended treatment for secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis using Cinacalcet (calcimimetic agent)?

Cinacalcet for Secondary Hyperparathyroidism in CKD Patients on Dialysis

Cinacalcet should be used as second-line therapy for secondary hyperparathyroidism in dialysis patients after optimization of vitamin D therapy and phosphate binders, with a recommended starting dose of 30 mg once daily taken with food. 1, 2

Treatment Algorithm

First-Line Therapy

• Optimize vitamin D therapy and phosphate binders 1
• Monitor PTH, calcium, and phosphorus levels

When to Consider Cinacalcet

• When patients on dialysis have elevated PTH despite optimized vitamin D therapy
• When surgical parathyroidectomy is contraindicated 1

Dosing and Administration

1. Starting dose: 30 mg once daily with food 2
2. Titration: Increase dose no more frequently than every 2-4 weeks
3. Sequential doses: 30,60,90,120, and 180 mg once daily 1, 2
4. Target: iPTH levels of 150-300 pg/mL 2

Monitoring

• Check serum calcium and phosphate within 1 week of initiation or dose adjustment
• Measure iPTH 1-4 weeks after initiation or dose adjustment
• Once maintenance dose is established, measure serum calcium monthly 1, 2
• Assess iPTH no earlier than 12 hours after dosing 2

Efficacy and Safety

Benefits

• Reduces risk of surgical parathyroidectomy by 51% (RR 0.49) 3, 1
• Effectively lowers PTH levels (43% reduction vs 9% increase with placebo) 4
• Improves calcium-phosphorus homeostasis (15% reduction in Ca×P product) 4

Limitations

• Little or no effect on all-cause mortality (RR 0.97) 3, 1
• Uncertain effects on cardiovascular mortality (RR 0.67) 3, 1

Common Adverse Effects

• Hypocalcemia (RR 6.98-7.38) 3, 1
• Gastrointestinal effects:
  • Nausea (RR 2.02-2.05) 3, 1
  • Vomiting (RR 1.97) 3
  • Diarrhea (RR 1.15) 1

Management of Hypocalcemia

If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur:

• Increase calcium-containing phosphate binders
• Increase vitamin D sterols 2

If serum calcium falls below 7.5 mg/dL or symptoms persist:

• Withhold cinacalcet until serum calcium reaches ≥8.0 mg/dL
• Resume treatment at the next lowest dose 2

Clinical Considerations and Caveats

Cost Considerations

• Cinacalcet is one of the most expensive drug costs for dialysis patients in the US 1
• Benefits may be limited to preventing parathyroidectomy in patients for whom surgery is contraindicated 1

When to Consider Parathyroidectomy

• Persistent hypercalcemic hyperparathyroidism despite optimized medical therapy
• Severe hyperparathyroidism with hypercalcemia/hyperphosphatemia refractory to medical therapy 1

Drug Interactions

• Strong CYP3A4 inhibitors may require cinacalcet dose adjustments 1

Common Pitfalls

1. Failing to monitor calcium levels frequently during dose titration
2. Titrating dose too rapidly (should be no more frequently than every 2-4 weeks)
3. Not taking cinacalcet with food (reduces bioavailability)
4. Using cinacalcet as first-line therapy before optimizing vitamin D and phosphate binders
5. Overlooking the risk of hypocalcemia, which occurs in approximately 6% of patients 3

Cinacalcet can be an effective component of therapy for secondary hyperparathyroidism in dialysis patients, particularly for preventing parathyroidectomy, but should be used judiciously given its cost and side effect profile.