Indications of Cinacalcet
Cinacalcet is primarily indicated for secondary hyperparathyroidism in adult patients with chronic kidney disease (CKD) on dialysis, hypercalcemia in patients with parathyroid carcinoma, and hypercalcemia in patients with primary hyperparathyroidism who cannot undergo parathyroidectomy. 1
FDA-Approved Indications
Secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis 1
- Important limitation: Not indicated for use in patients with CKD who are not on dialysis due to increased risk of hypocalcemia 1
Hypercalcemia in adult patients with parathyroid carcinoma 1
Hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated based on serum calcium levels, but who are unable to undergo the surgery 1
Clinical Evidence for Secondary Hyperparathyroidism in CKD
Cinacalcet reduces the risk of surgical parathyroidectomy (RR 0.49 [95% CI, 0.40-0.59]) in patients with CKD stage 5D 2
Treatment shows little or no effect on all-cause mortality (RR 0.97 [95% CI, 0.89-1.05]) and uncertain effects on cardiovascular mortality (RR 0.67 [95% CI, 0.16-2.87]) 2
Cinacalcet effectively reduces PTH levels (mean difference -281 ng/L) and calcium concentrations (mean difference -0.22 mmol/L) 2
The medication prevents hypercalcemia (RR 0.23 [95% CI, 0.05-0.97]) but significantly increases risk of hypocalcemia (RR 7.38 [95% CI, 5.43-10.03]) 2
Practical Application Guidelines
UK National Health Service National Institute for Health and Clinical Excellence (NICE) recommends limiting cinacalcet use to people with elevated PTH concentrations refractory to standard therapy, with normal or high serum calcium, and in whom surgical parathyroidectomy is contraindicated 3
US FDA approval aligns with this approach, restricting use to patients with CKD stage 5D who have secondary hyperparathyroidism, with benefits primarily limited to prevention of surgical parathyroidectomy and avoidance of hypercalcemia 3
Available evidence does not support the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggesting that people with CKD on dialysis and elevated PTH levels should receive calcimimetics to decrease serum PTH levels 3
Efficacy in Clinical Practice
On average, treating 1,000 people with CKD stage 5D for 1 year:
- Has no effect on survival
- Prevents approximately 3 patients from requiring parathyroidectomy
- Leads to approximately 60 cases of hypocalcemia
- Results in approximately 150 cases of nausea 2
Cinacalcet helps more patients achieve Kidney Disease Outcomes Quality Initiative (KDOQI) targets for PTH, calcium, and calcium-phosphorus product compared to conventional therapy 4
Common Adverse Effects
Gastrointestinal effects are most common: nausea (RR 2.02 [95% CI, 1.45-2.81]), vomiting (RR 1.97 [95% CI, 1.73-2.24]), and diarrhea (RR 1.15 [95% CI, 1.02-1.29]) 2
Hypocalcemia is a significant risk (RR 6.98 [95% CI, 5.10-9.53]) 2
Most adverse events are mild to moderate in severity and often transient 5
Important Clinical Considerations
Routine use of cinacalcet in people with CKD does not appear warranted based on current evidence 3
Benefits may be limited to preventing parathyroidectomy in patients for whom surgery is contraindicated 3
Data for cinacalcet therapy are largely limited to adults with CKD stage 5D, with insufficient evidence for other CKD stages 3
Evidence for patients receiving peritoneal dialysis is limited, making treatment estimates for this specific group less certain 3
Cinacalcet should be taken with food or shortly after a meal to increase bioavailability 6