cinacalcet
Brand: Sensipar
Prototype Drug
Drug Class: calcimimetic
Drug Family: bone agent
Subclass: calcium-sensing receptor (CaSR) agonist
Organ Systems: renalendocrine
Mechanism of Action
Positive allosteric modulator of CaSR; increases sensitivity to extracellular calcium, suppressing PTH synthesis and secretion; reduces calcium and phosphorus levels.
calcium-sensing receptor (CaSR) on parathyroid cells
Indications
- secondary hyperparathyroidism in dialysis patients with CKD
- primary hyperparathyroidism (inoperable)
- parathyroid carcinoma
Contraindications
- hypocalcemia (serum Ca2+ <8.4 mg/dL)
Adverse Effects
Common
- nausea
- vomiting
- hypocalcemia
- diarrhea
- myalgia
Serious
- severe hypocalcemia (seizures, arrhythmias)
- worsening HF (hypocalcemia)
Pharmacokinetics (ADME)
| Absorption | ~20-25% oral bioavailability |
| Distribution | large Vd — lipophilic |
| Metabolism | extensive hepatic CYP3A4 |
| Excretion | renal 65% (as metabolites) |
| Half-life | 30-40 hours |
| Onset | 2-6 hours |
| Peak | 2-6 hours |
| Duration | 24 hours |
| Protein Binding | 97% |
| Vd | large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors | increases cinacalcet — dose adjust | major |
| CYP2D6 substrates (amitriptyline, metoprolol) | cinacalcet inhibits CYP2D6 — increases their levels | moderate |
Nursing Considerations
- Take with food to improve absorption and reduce nausea
- Monitor serum calcium and phosphorus within 1 week of initiation or dose changes
- Hold if serum calcium <7.5 mg/dL until corrected
- EVOLVE trial: cinacalcet did not reduce CV mortality in dialysis patients (trend only)
Clinical Pearls
- First-in-class calcimimetic: increases parathyroid cell sensitivity to ambient calcium without adding calcium load
- EVOLVE trial: no significant reduction in CV mortality but reduced parathyroid surgery rate and calcium/phosphorus levels
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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