When to add cinacalcet (Sensipar) to the treatment regimen of a patient with Chronic Kidney Disease (CKD) stage 5 on dialysis with elevated intact Parathyroid Hormone (PTH) levels?

When to Add Cinacalcet in CKD Stage 5 on Dialysis

Cinacalcet should be initiated in CKD stage 5D (dialysis) patients when PTH levels are persistently elevated (typically >300 pg/mL) despite optimization of vitamin D and phosphate binders, with the primary goal being prevention of parathyroidectomy rather than improvement in mortality. 1, 2

FDA-Approved Indications and Starting Criteria

• Start cinacalcet at 30 mg once daily in dialysis patients with secondary hyperparathyroidism when PTH remains elevated despite conventional therapy 3
• The FDA specifically approves cinacalcet for CKD stage 5D patients, with benefits primarily limited to preventing surgical parathyroidectomy (RR 0.49) and avoiding hypercalcemia (RR 0.23) 1, 2
• Target PTH range is 150-300 pg/mL, though routine use to achieve arbitrary PTH targets is not warranted based on current evidence 1, 3

Clinical Scenarios for Initiation

When PTH is severely elevated (≥500 pg/mL):

• Cinacalcet demonstrates greatest effectiveness in patients with iPTH ≥500 pg/mL, reducing all-cause mortality by approximately 50% (IRR 0.49) in this subgroup 4
• This represents the population most likely to benefit from treatment beyond just PTH reduction 4

When parathyroidectomy is being considered but contraindicated:

• Cinacalcet prevents approximately 3 parathyroidectomies per 1,000 patients treated for one year 1
• Consider cinacalcet as a bridge or alternative when surgical risks outweigh benefits due to comorbidities 2

When hypercalcemia complicates vitamin D therapy:

• Cinacalcet reduces hypercalcemia risk (RR 0.23) and allows continued PTH management when vitamin D analogues cause problematic calcium elevations 1, 2

Titration Protocol

• Measure serum calcium and phosphorus within 1 week, and iPTH 1-4 weeks after initiation 3
• Titrate no more frequently than every 2-4 weeks through sequential doses: 30 → 60 → 90 → 120 → 180 mg once daily 3
• Assess iPTH no earlier than 12 hours after dosing, as steady-state is reached within 7 days of dose changes 3
• Cinacalcet can be used alone or combined with vitamin D sterols and/or phosphate binders 3

Critical Safety Monitoring

Hypocalcemia is the most significant risk:

• Occurs in approximately 60 per 1,000 patients treated annually (RR 7.38) 1, 5
• If calcium falls below 8.4 mg/dL but remains >7.5 mg/dL: increase calcium-containing phosphate binders and/or vitamin D 3
• If calcium falls below 7.5 mg/dL or symptomatic hypocalcemia persists: withhold cinacalcet until calcium reaches 8 mg/dL, then restart at next lowest dose 3
• Monitor calcium monthly once maintenance dose is established 3

Gastrointestinal side effects:

• Nausea occurs in approximately 150 per 1,000 patients (RR 2.02) and vomiting in similar proportions (RR 1.97) 1, 5
• These effects are common but usually manageable and should not preclude appropriate use 1

Important Caveats and Limitations

• Cinacalcet does not improve all-cause mortality (RR 0.97) or cardiovascular mortality (RR 0.67) in the overall dialysis population 6, 1, 2
• Treatment is aimed at preventing parathyroidectomy and managing mineral metabolism, not improving survival 2
• Routine use in all dialysis patients with elevated PTH is not warranted by current evidence 6, 1
• Data are largely limited to hemodialysis patients; evidence in peritoneal dialysis is less certain 6, 1
• Do not use cinacalcet in CKD stages 3-4 (non-dialysis) as this is off-label with insufficient evidence for routine use 1, 7

When NOT to Initiate

• Avoid if corrected serum calcium is below the lower limit of normal at baseline 3
• Do not start if patient has moderate-to-severe hepatic impairment without dose adjustment considerations (AUC increases 2.4-4 fold) 3
• Reconsider if PTH is <300 pg/mL and patient has no hypercalcemia or impending need for parathyroidectomy 1, 4