1. Clinical Overview
Cinacalcet is a calcimimetic agent that acts as an allosteric modulator of the calcium-sensing receptor (CaSR) on parathyroid cells. It increases the sensitivity of the CaSR to extracellular calcium, leading to a reduction in parathyroid hormone (PTH) secretion. It is a cornerstone therapy for secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on dialysis and for hypercalcemia in patients with parathyroid carcinoma.
| Onset | Duration | Bioavailability |
|---|---|---|
| PTH reduction observed within 2-4 hours of administration. | Approximately 24 hours, supporting once-daily dosing. | Approximately 20-25% when taken with a high-fat meal. |
2. Mechanism of Action
Cinacalcet is a positive allosteric modulator of the calcium-sensing receptor (CaSR), a G-protein coupled receptor primarily located on the surface of chief cells of the parathyroid gland. By binding to a site distinct from the endogenous ligand (calcium), it increases the receptor's sensitivity to extracellular calcium ions. This enhanced activation of the CaSR inhibits the synthesis and secretion of parathyroid hormone (PTH). Lower PTH levels decrease bone resorption and renal tubular reabsorption of calcium, thereby lowering serum calcium and phosphorus levels.
3. Indications & Uses
- Secondary Hyperparathyroidism (SHPT) in adult patients with Chronic Kidney Disease (CKD) on maintenance dialysis
- Hypercalcemia in patients with Parathyroid Carcinoma
4. Dosage & Administration
Adult Dosage: SHPT (CKD on dialysis): Start at 30 mg once daily. Titrate every 2-4 weeks sequentially through 30 mg, 60 mg, 90 mg, 120 mg, and 180 mg once daily to achieve intact PTH (iPTH) between 150-300 pg/mL. Dose adjustments based on iPTH and serum calcium. Parathyroid Carcinoma: Start at 30 mg twice daily. Titrate every 2-4 weeks through 30 mg bid, 60 mg bid, 90 mg bid to a maximum of 90 mg four times daily as needed to normalize serum calcium.
Administration: Must be taken with food or shortly after a meal to improve bioavailability. Tablet should be swallowed whole, not divided, crushed, or chewed. Should be taken at the same time each day. Serum calcium must be monitored within 1 week of initiation or dose adjustment.
5. Side Effects
Common side effects may include:
- Nausea
- Vomiting
- Diarrhea
- Myalgia (muscle pain)
- Dizziness
- Asthenia (weakness)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Ketoconazole, Itraconazole, Voriconazole | Potent CYP3A4 inhibitors increase cinacalcet AUC by 2-3 fold. Risk of hypocalcemia and adverse effects. | Major |
| Erythromycin, Clarithromycin | Moderate CYP3A4 inhibitors. May increase cinacalcet levels. Monitor closely. | Moderate |
| Rifampicin, Carbamazepine, Phenytoin, St. John's Wort | Potent CYP3A4 inducers decrease cinacalcet levels significantly, reducing efficacy. | Major |
| Flecainide, Tricyclic Antidepressants (e.g., Amitriptyline) | Cinacalcet is a moderate inhibitor of CYP2D6. Can increase levels of these CYP2D6 substrates. | Moderate |
| Vitamin D analogues (Calcitriol, Paricalcitol) | Additive effect on lowering PTH. Increased risk of hypocalcemia, especially during cinacalcet initiation/titration. Doses of vitamin D may need reduction. | Moderate |
| Drugs that prolong QT interval (e.g., certain antiarrhythmics, antipsychotics) | Hypocalcemia caused by cinacalcet can exacerbate QT prolongation, increasing arrhythmia risk. | Major |
7. Patient Counselling
- DO take the tablet with food or immediately after a meal.
- DO swallow the tablet whole. Do not break, crush, or chew it.
- DO have your blood tests (calcium, phosphorus, PTH) done regularly as advised by your doctor.
- DO inform all your doctors and pharmacists that you are taking cinacalcet.
- DONT take the medicine on an empty stomach.
- DONT adjust your dose or stop taking the medicine without consulting your doctor, even if you feel well.
- DONT start any new medicine, including over-the-counter drugs or herbal supplements, without checking with your doctor.
8. Toxicology & Storage
Overdose: Primarily related to hypocalcemia: paresthesia, myalgia, cramping, tetany, seizures, confusion, prolonged QT interval, cardiac arrhythmias, and hypotension.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture. Keep in the original blister pack or container. Keep out of reach of children.