When to initiate cinacalcet (Sensipar) treatment in a patient with secondary hyperparathyroidism on hemodialysis?

When to Initiate Cinacalcet in Hemodialysis Patients with Secondary Hyperparathyroidism

Cinacalcet should NOT be used as routine first-line therapy for elevated PTH in hemodialysis patients, but should be reserved for patients with persistently elevated PTH (>300 pg/mL) that remains refractory to standard therapy with vitamin D sterols and phosphate binders, particularly when serum calcium is normal or elevated and surgical parathyroidectomy is contraindicated. 1

Pre-Treatment Requirements and Contraindications

Before initiating cinacalcet, you must verify the following absolute requirements:

• Serum calcium must be at or above the lower limit of normal (≥8.4 mg/dL) - cinacalcet initiation is contraindicated if calcium is below normal range 2
• Patient must be on dialysis - cinacalcet is not indicated for CKD patients not on dialysis 2
• iPTH levels should be >300 pg/mL despite optimization of conventional therapy 3, 4

Clinical Indications for Initiation

Cinacalcet is appropriate when ALL of the following criteria are met:

• Refractory hyperparathyroidism: PTH remains elevated (>300 pg/mL) despite adequate trials of vitamin D sterols and phosphate binders 1
• Normal or elevated serum calcium: Patients with hypercalcemia benefit most, as cinacalcet reduces calcium levels by 6-7% 5
• Parathyroidectomy contraindicated or refused: Surgery remains the definitive treatment when feasible 1
• Target iPTH range: Goal is to achieve iPTH levels of 150-300 pg/mL per KDOQI guidelines 2

Evidence Supporting Restricted Use

The UK National Institute for Health and Clinical Excellence guidance explicitly states cinacalcet should NOT be used for routine treatment of elevated PTH, based on the following evidence:

• No mortality benefit: Cinacalcet shows little or no effect on all-cause mortality (treating 1,000 patients for 1 year prevents zero deaths) 6
• Uncertain cardiovascular benefit: Effects on cardiovascular death remain uncertain 1
• Small parathyroidectomy reduction: Only prevents 3 parathyroidectomies per 1,000 patients treated for 1 year (RR 0.49) 6, 1
• Significant adverse effects: Causes hypocalcemia in 60 per 1,000 patients (7-fold increased risk, RR 7.38) and nausea in 150 per 1,000 patients (RR 2.05) 6, 7

Dosing and Monitoring Protocol

When criteria are met and cinacalcet is initiated:

• Starting dose: 30 mg once daily, taken with food or shortly after a meal 2
• Tablets must be swallowed whole - never crushed, chewed, or divided 2
• Titration schedule: Increase no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 2
• Early monitoring: Measure serum calcium and phosphorus within 1 week, and iPTH 1-4 weeks after initiation or dose adjustment 2
• iPTH timing: Assess iPTH no earlier than 12 hours after dosing 2
• Maintenance monitoring: Once stable, check calcium monthly 2

Critical Safety Considerations

Hypocalcemia is the most significant safety concern and requires vigilant monitoring:

• If calcium falls below 8.4 mg/dL but remains >7.5 mg/dL: Increase calcium-containing phosphate binders and/or vitamin D sterols 2
• If calcium falls below 7.5 mg/dL: Withhold cinacalcet immediately until calcium reaches ≥8.0 mg/dL, then restart at next lowest dose 2
• Hypocalcemia can prolong QT interval, lower seizure threshold, and cause hypotension, worsening heart failure, and arrhythmias 2

Common Pitfalls to Avoid

• Do not use as first-line therapy: The generally negative findings on patient-level endpoints mean cinacalcet should only be used when standard therapy fails 6
• Do not initiate with low calcium: This is an absolute contraindication that increases risk of life-threatening hypocalcemia 2
• Do not use in non-dialysis CKD: Evidence is scant and very low quality for CKD stages 3-5, and benefits are likely smaller than in dialysis populations 6
• Anticipate GI side effects: Nausea (RR 2.05) and vomiting (RR 1.95) are common, especially at treatment initiation, but are usually mild to moderate and transient 7, 5

Alternative Considerations

• Etelcalcetide: If switching from etelcalcetide to cinacalcet, discontinue etelcalcetide for at least 4 weeks and ensure corrected calcium is at or above lower limit of normal before starting cinacalcet at 30 mg once daily 2
• Vitamin D sterols: Can be used in combination with cinacalcet without restriction 2, 8