Is cinacalcet (Sensipar) a parathyroid hormone (PTH) regulator?

From the Guidelines

No, cinacalcet is not a parathyroid hormone (PTH), but rather a calcimimetic medication that acts on the calcium-sensing receptors in the parathyroid gland to reduce PTH secretion. Cinacalcet works by increasing the sensitivity of these receptors to extracellular calcium, which tricks the parathyroid gland into sensing higher calcium levels than actually exist in the bloodstream, leading to decreased production and release of PTH. According to the most recent and highest quality study available, the EVOLVE trial 1, cinacalcet provides small absolute benefits for parathyroidectomy, but has little or no effect on all-cause mortality and uncertain effects on cardiovascular death for people with chronic kidney disease (CKD).

Key Points

• Cinacalcet is primarily used to treat secondary hyperparathyroidism in patients with CKD on dialysis, primary hyperparathyroidism, and parathyroid carcinoma.
• The typical starting dose is 30 mg once daily, which may be titrated every 2-4 weeks to achieve target PTH levels.
• Common side effects include nausea, vomiting, and hypocalcemia.
• Regular monitoring of calcium, phosphorus, and PTH levels is necessary during treatment.
• The current evidence suggests that cinacalcet should not be used for the routine treatment of elevated serum PTH levels in people with CKD and should be limited to people with elevated PTH concentrations refractory to standard therapy, with a normal or high serum calcium concentration, and in whom surgical parathyroidectomy is contraindicated 1.

Treatment Considerations

• The choice of treatment should be guided by individual considerations about concomitant therapies and the patient's current calcium and phosphate levels.
• The revised recommendation for PTH-lowering therapy in patients with CKD stage G5D now lists all acceptable treatment options in alphabetical order, including calcimimetics, calcitriol, or vitamin D analogues, or a combination of these therapies 1.

From the FDA Drug Label

The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH synthesis and secretion. Cinacalcet, the active ingredient in cinacalcet tablets, is a calcimimetic agent that directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium.

Cinacalcet is a calcimimetic agent that lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium.

• It is used to treat secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
• The reduction in PTH is associated with a concomitant decrease in serum calcium levels.
• Cinacalcet has been shown to be effective in reducing iPTH levels in patients with CKD on dialysis, with approximately 40% of patients achieving an iPTH ≤ 250 pg/mL 2.
• The medication works by modulating the calcium-sensing receptor, which is the principal regulator of PTH synthesis and secretion.

From the Research

Cinacalcet and PTH

• Cinacalcet is a calcimimetic agent that acts on the calcium-sensing receptor to increase its sensitivity to calcium, thereby reducing parathyroid hormone (PTH) secretion 3, 4, 5, 6, 7.
• Studies have shown that cinacalcet is effective in reducing PTH levels in patients with secondary hyperparathyroidism, including those on dialysis and those not on dialysis 3, 4, 5, 6, 7.
• The mechanism of action of cinacalcet differs from that of vitamin D sterols, which are traditionally used to treat secondary hyperparathyroidism, and it has been shown to lower plasma PTH levels without increasing serum calcium and phosphorus levels 6.

Effects of Cinacalcet on PTH

• Cinacalcet has been shown to reduce PTH levels by 30-50% in patients with secondary hyperparathyroidism 3, 4, 5.
• The reduction in PTH levels is associated with a decrease in serum calcium, phosphorus, and calcium-phosphorus product levels 3, 5.
• Cinacalcet has also been shown to reduce the risk of parathyroidectomy, fracture, and hospitalization for cardiovascular complications in patients with secondary hyperparathyroidism 5.

Cinacalcet as a Treatment for Secondary Hyperparathyroidism

• Cinacalcet is a novel treatment for secondary hyperparathyroidism in patients with chronic kidney disease, including those on dialysis and those not on dialysis 3, 4, 5, 6, 7.
• Cinacalcet offers a new therapeutic approach to the treatment of secondary hyperparathyroidism, with a mechanism of action that targets the calcium-sensing receptor 5, 6, 7.
• The use of cinacalcet has been shown to be effective and safe in reducing PTH levels and improving calcium and phosphorus homeostasis in patients with secondary hyperparathyroidism 3, 4, 5, 6, 7.