Calcimimetics

Calcimimetics are a class of drugs that modulate the activity of the calcium-sensing receptor (CaSR) on the parathyroid gland. By increasing the receptor’s sensitivity to extracellular calcium, they reduce parathyroid hormone (PTH) secretion, which lowers serum calcium and phosphate levels and decreases bone turnover.

The two main agents in clinical use are cinacalcet and etelcalcetide. Cinacalcet is an oral small-molecule calcimimetic that activates CaSR on parathyroid cells. Etelcalcetide is a synthetic peptide given by intravenous infusion, typically at the end of a hemodialysis session, and also targets CaSR to reduce PTH release.

Indications: Calcimimetics are used in adults with chronic kidney disease who have secondary hyperparathyroidism, particularly in those on dialysis. Cinacalcet is approved for secondary hyperparathyroidism and, in some settings, for hypercalcemia associated with parathyroid carcinoma; etelcalcetide is approved specifically for secondary hyperparathyroidism in adults receiving regular hemodialysis.

Monitoring and safety: Treatment requires regular laboratory monitoring of calcium, phosphate, and PTH levels. Hypocalcemia is the principal adverse effect, and other common side effects can include nausea, vomiting, diarrhea, and headache. Dose adjustments are guided by laboratory values and clinical response.

Relation to other therapies: Calcimimetics are used when PTH remains high despite phosphate binders and vitamin D analogs, or when hypercalcemia limits the use of other therapies. They are part of the broader management strategy for CKD-related mineral and bone disorders.