What is the dosing and duration of cinacalcet (calcimimetic) therapy, and when should it be decreased or stopped?

From the Guidelines

Cinacalcet therapy should be limited to patients with secondary hyperparathyroidism who are refractory to standard therapy, have a normal or high serum calcium concentration, and in whom surgical parathyroidectomy is contraindicated, due to its limited benefits and potential for adverse effects, as evidenced by the 2013 meta-analysis published in PLoS Medicine 1. The dosing of cinacalcet typically starts at 30 mg once daily, with dose adjustments made every 2-4 weeks based on serum calcium and parathyroid hormone (PTH) levels, as supported by the study 1. Key considerations for cinacalcet therapy include:

• Starting dose: 30 mg once daily
• Dose titration: every 2-4 weeks based on serum calcium and PTH levels
• Target PTH levels: 150-300 pg/mL for patients with secondary hyperparathyroidism on dialysis
• Monitoring: regular monitoring of calcium, phosphorus, and PTH levels, typically every 1-2 weeks during dose titration and then monthly once stable
• Potential side effects: nausea, vomiting, hypocalcemia, and gastrointestinal symptoms
• Indications for decrease or discontinuation: serum calcium below 8.4 mg/dL, hypocalcemic symptoms, or PTH suppression below target range It is essential to weigh the potential benefits of cinacalcet against its risks and consider alternative treatment options, as the current evidence suggests that routine use of cinacalcet therapy in people with CKD does not appear warranted, according to the study 1.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Administration Cinacalcet tablets should be taken with food or shortly after a meal. 2.2 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis The recommended starting oral dose of cinacalcet tablets is 30 mg once daily. Cinacalcet tablets should be titrated no more frequently than every 2 to 4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH levels of 150 to 300 pg/mL. 2.3 Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism The recommended starting oral dose of cinacalcet tablets is 30 mg twice daily. 2.4 Switching from Parsabiv (etelcalcetide) to Cinacalcet Tablets Discontinue etelcalcetide for at least 4 weeks prior to starting cinacalcet tablets. 2.5 Monitoring for Hypocalcemia Once the maintenance dose has been established, serum calcium should be measured approximately monthly for patients with secondary hyperparathyroidism with CKD on dialysis, and every 2 months for patients with parathyroid carcinoma or primary hyperparathyroidism.

The dosing of cinacalcet is as follows:

• Starting dose: 30 mg once daily for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, and 30 mg twice daily for patients with parathyroid carcinoma and primary hyperparathyroidism.
• Titration: The dose should be titrated every 2 to 4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily for secondary hyperparathyroidism, and 30 mg twice daily, 60 mg twice daily, and 90 mg twice daily, and 90 mg 3 or 4 times daily as necessary for parathyroid carcinoma and primary hyperparathyroidism.
• Duration: The duration of therapy is not explicitly stated, but it is recommended to monitor serum calcium levels approximately monthly for patients with secondary hyperparathyroidism with CKD on dialysis, and every 2 months for patients with parathyroid carcinoma or primary hyperparathyroidism.
• Decrease or stop: Cinacalcet should be decreased or stopped if serum calcium falls below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased. Treatment should be reinitiated using the next lowest dose of cinacalcet tablets once serum calcium levels reach 8 mg/dL and/or symptoms of hypocalcemia have resolved 2.

From the Research

Dosing and Duration of Cinacalcet Therapy

• The dosing of cinacalcet varies depending on the patient's response and serum calcium levels. In a study published in the Journal of endocrinological investigation 3, the maintenance cinacalcet dose was a median of 30 mg twice daily, with a range of 30 mg daily to 60 mg twice daily.
• The duration of cinacalcet therapy can be long-term, with some studies showing treatment durations of up to 12 months 3 or even 136 weeks 4.
• Cinacalcet can be effective in reducing serum calcium levels in patients with primary hyperparathyroidism (PHPT), with one study showing a reduction in serum calcium of at least 1 mg/dl in all patients, and normalization of serum calcium in 10 out of 14 patients 3.

When to Decrease or Stop Cinacalcet Therapy

• Cinacalcet therapy should be decreased or stopped if the patient experiences adverse events, such as nausea, vomiting, or paresthesias, which are common side effects of the medication 4, 5.
• The therapy should also be decreased or stopped if the patient's serum calcium levels become too low, as hypocalcemia can be associated with an increased risk of cardiovascular mortality 6.
• In patients with PHPT, cinacalcet therapy can be stopped if the patient undergoes parathyroidectomy, as surgery is usually curative for this condition.

Combination Therapy with Other Medications

• Cinacalcet can be used in combination with other medications, such as alendronate, to improve bone mineral density in patients with PHPT 7.
• The combination of cinacalcet and alendronate has been shown to be effective in normalizing hypercalcemia and improving bone mineral density in patients with PHPT, while cinacalcet monotherapy is less effective on bone mineral density 7.