Calcimimetics are medications that mimic the action of calcium on tissues, particularly in the parathyroid gland. By activating calcium-sensing receptors, calcimimetics inhibit the release of parathyroid hormone. Due to this mechanism, this drug class is mainly indicated for management of hyperparathyroidism. Adverse effects include hypocalcemia, GI symptoms, adynamic bone disease, and QT prolongation. Cinacalcet is metabolized by the cytochrome P450 (CYP450) system, which results in several drug interactions.

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Medications in the class

  • Cinacalcet: 1st drug in the class
  • Etelcalcetide: recently approved

Mechanism of action

  • Calcium-sensing receptor (CaSR):
    • G-protein-coupled receptor 
    • Responds to alterations in extracellular calcium concentrations
    • Examples: 
      • ↓ Serum calcium → parathyroid hormone (PTH) release → calcium release from bone
      • ↑ Serum calcium → ↑ calcium binding on CaSR → PTH release is inhibited
  • Calcimimetics activate CaSR on the parathyroid gland → inhibit PTH secretion
  • This leads to:
    • ↓ Serum calcium
    • ↓ Serum phosphorus

Physiologic effects

Calcimimetics prevent the progression of bone disease and adverse effects associated with hyperparathyroidism.



  • Cinacalcet
    • Given orally
    • Rapidly absorbed
    • Food increases absorption.
  • Etelcalcetide: given intravenously

Distribution and metabolism

  • Cinacalcet: 
    • Highly protein bound
    • Metabolized by the cytochrome P450 (CYP450) system
  • Etelcalcetide:
    • Forms conjugates with albumin
    • Not metabolized by CYP450 enzymes


  • Cleared renally
  • ↓ Clearance in patients with renal disease


  • Cinacalcet:
    • Primary hyperparathyroidism 
      • Helps treat hypercalcemia
      • Used in patients who cannot undergo parathyroidectomy
      • Bisphosphonates are a better choice in patients with osteoporosis.
    • Secondary hyperparathyroidism: 
      • In patients with chronic kidney disease (on dialysis)
      • Studies suggest a ↓ risk of fractures
    • Parathyroid carcinoma: treatment of hypercalcemia
  • Etelcalcetide: secondary hyperparathyroidism in patients with CKD on hemodialysis

Adverse Effects and Contraindications

Adverse effects

Important adverse effects for the calcimimetic class include:

  • Hypocalcemia (more common with etelcalcetide)
  • Nausea and vomiting 
  • Diarrhea 
  • Dizziness
  • Prolonged QTc on ECG
  • Adynamic bone disease (↓ bone turnover due to chronic PTH suppression)


  • Hypersensitivity to the drug or its components
  • Serum calcium < the lower limit of the normal

Drug interactions

  • Cinacalcet may cause interactions through CYP450:
    • ↑ Concentrations of:
      • Propranolol and carvedilol
      • Risperidone and haloperidol
      • Amitriptyline and nortriptyline
      • Amphetamines
      • Doxorubicin
    • ↓ Concentrations of:
      • Tamoxifen
      • Tacrolimus
  • Etelcalcetide: denosumab can ↑ the hypocalcemic effect


Calcium levels should be monitored.

Comparison of Drug Classes

Table: Comparison of drug classes used in the management of hyperparathyroidism
Drug class Mechanism of action Indications Adverse effetcs
Bisphosphonates ↓ Bone resorption Improve BMD in primary hyperparathyroidism*
  • Hypocalcemia
  • Hypophosphatemia
  • Esophagitis
  • Avascular necrosis
  • Osteonecrosis of the jaw
  • Mimic calcium’s effect on CaSR
  • ↓ PTH release
Primary* and secondary hyperparathyroidism with hypercalcemia
  • Hypocalcemia
  • GI effects
  • QT prolongation
  • Adynamic bone disease
Vitamin D and analogs
  • Activate VDR
  • ↑ Calcium levels
  • ↓ PTH release
Secondary hyperparathyroidism with normal or ↓ serum calcium
  • Hypocalcemia
  • Hyperphosphatemia
* Medical therapy is indicated for primary hyperparathyroidism when surgery is not an option.
BMD: bone mineral density
VDR: vitamin D receptors


  1. Cinacalcet (Drug information). UpToDate.
  2. Etelcalcetide (Drug information). UpToDate.
  3. Pereira, L, Meng, C, Marques, D, & Frazao, JM. (2018). Old and new calcimimetics for treatment of secondary hyperparathyroidism: Impact on biochemical and relevant clinical outcomes. Clinical Kidney Journal. Oxford Academic.
  4. Etelcalcetide (Rx). Medscape.
  5. Urena, P, Legoupil, N, & De Vernejoul, MC. (2005). Calcimimetics, mechanism of action, and therapeutic applications. NCBI.
  6. Goodman, WG. (2002). Calcimimetic agents and secondary hyperparathyroidism: Treatment and prevention” Nephrology Dialysis Transplantation. 17: 204–207.
  7. Silverberg, SJ, & Fuleihan, GE. (2019). Primary hyperparathyroidism: Management. In Mulder, J.E. (Ed.), UpToDate. Retrieved July 4, 2021, from
  8. Quarles, LD, & Berkoben, M. (2021). Management of secondary hyperparathyroidism in adult dialysis patients. In Motwani, S. (Ed.), UpToDate. Retrieved July 4, 2021, from
  9. Junaid, Z, & Patel, J. (2020). Cinacalcet. [Online] StatPearls. Retrieved July 4, 2021, from

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