What is the recommended dosage of cinacalcet (calcimimetic agent) for parathyroid hormone control?

Cinacalcet Dosage for Parathyroid Hormone Control

The recommended starting dose of cinacalcet for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis is 30 mg once daily, with titration every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150-300 pg/mL. 1

Dosing Guidelines by Condition

Secondary Hyperparathyroidism in CKD on Dialysis

• Start with 30 mg once daily with food or shortly after a meal 1
• Monitor serum calcium and phosphorus within 1 week and iPTH 1-4 weeks after initiation or dose adjustment 1
• Titrate dose no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 1
• Target iPTH levels of 150-300 pg/mL 1
• Assess serum iPTH levels no earlier than 12 hours after dosing 1

Parathyroid Carcinoma and Primary Hyperparathyroidism

• Start with 30 mg twice daily 1
• Titrate every 2-4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg 3-4 times daily as necessary 1
• Goal is to normalize serum calcium levels 1
• Monitor serum calcium within 1 week after initiation or dose adjustment 1

X-Linked Hypophosphatemia with Secondary Hyperparathyroidism

• Consider cinacalcet as adjuvant treatment in patients with persistently elevated PTH levels despite optimization of active vitamin D and phosphate doses 2
• Use with caution as cinacalcet has been associated with severe adverse effects including hypocalcemia and increased QT interval 2
• No specific dosing recommendation is provided for this indication, suggesting that standard dosing protocols should be followed 2

Monitoring and Dose Adjustments

Laboratory Monitoring

• Serum calcium and phosphorus: within 1 week of initiation or dose change 1
• iPTH: 1-4 weeks after initiation or dose change 1
• Once maintenance dose established: monthly calcium monitoring for secondary hyperparathyroidism, every 2 months for parathyroid carcinoma or primary hyperparathyroidism 1

Hypocalcemia Management

• 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 and/or vitamin D sterols 1
• If serum calcium falls below 7.5 mg/dL or symptoms persist: withhold cinacalcet until serum calcium reaches 8 mg/dL and/or symptoms resolve 1
• Restart at the next lowest dose 1

Efficacy and Safety Considerations

Efficacy

• In long-term studies, approximately 55% of patients achieved PTH concentration ≤300 pg/mL and about 60% had at least a 30% reduction in PTH from baseline 3
• In a one-year study, 61.6% of patients achieved iPTH ≤250 pg/mL compared to 9.9% in the control group 4
• For primary hyperparathyroidism, cinacalcet effectively reduces serum calcium in 65-80% of patients 5

Common Adverse Effects

• Gastrointestinal: nausea (13%), vomiting (9%), dyspepsia (5%), diarrhea (5%) 4
• Hypocalcemia (11%) 4
• Increased risk of hypocalcemia (RR 7.38), nausea (RR 2.05), vomiting (RR 1.95), and diarrhea (RR 1.15) 2

Special Considerations

Low-Dose Approach for Primary Hyperparathyroidism

• For patients with primary hyperparathyroidism not eligible for surgery, low-dose cinacalcet (starting at 30 mg/day) can effectively normalize serum calcium in most patients 6
• Dose adjustments should be based on calcemia reduction and drug tolerance 6

Cautions

• Cinacalcet should be used with caution in X-linked hypophosphatemia due to risk of severe hypocalcemia and increased QT interval 2
• Benefits in CKD may be limited to preventing parathyroidectomy in patients for whom surgery is contraindicated 2
• Cinacalcet has little or no effect on all-cause mortality (RR 0.97) in end-stage CKD 2

Administration

• Cinacalcet tablets should always be taken with food or shortly after a meal 1
• Tablets should always be taken whole and not chewed, crushed, or divided 1
• When switching from etelcalcetide, discontinue for at least 4 weeks prior to starting cinacalcet 1

By following these dosing guidelines and monitoring protocols, clinacalcet can effectively control parathyroid hormone levels while minimizing adverse effects. The dosing strategy should be tailored based on the specific condition being treated and the patient's response to therapy.