CINACALCET HYDROCHLORIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Allosteric activator of the calcium-sensing receptor (CaSR) on parathyroid chief cells, increasing sensitivity to extracellular calcium and reducing parathyroid hormone (PTH) secretion.
| Metabolism | Hepatic via CYP3A4, CYP2D6, and CYP1A2; major metabolites are inactive. |
| Excretion | Renal: 80% (as metabolites), Fecal: 15%, Biliary: negligible. |
| Half-life | Terminal elimination half-life: 30–40 hours in patients with normal renal function; prolonged to 42–83 hours in moderate to severe hepatic impairment. Steady-state reached within 7 days. |
| Protein binding | 97% bound to albumin. |
| Volume of Distribution | Approximately 1.7 L/kg (1000 L for 70 kg person), indicating extensive tissue distribution. |
| Bioavailability | 76–82% (oral); food increases AUC by 50–80%. |
| Onset of Action | Oral: Serum calcium reduction begins within 2 hours; maximal reduction by 4–6 hours. |
| Duration of Action | Serum calcium reduction persists for 24 hours after a single dose; with chronic dosing, maintains reduced calcium for duration of therapy. |
30 mg orally once daily, titrate every 2-4 weeks to a maximum of 180 mg once daily to achieve target intact parathyroid hormone (iPTH) level.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment, including end-stage renal disease (ESRD) on dialysis. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no dose adjustment. Moderate to severe hepatic impairment (Child-Pugh B or C): reduce starting dose to 30 mg daily and monitor iPTH and serum calcium closely. |
| Pediatric use | Not established for pediatric patients; safety and efficacy in children have not been determined. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged 65 and older, but no overall differences in safety or efficacy were observed. Use with caution due to potential for increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause hypocalcemia monitor serum calcium levels closely.
| Breastfeeding | No data on presence in human milk. In lactating rats, cinacalcet was excreted in milk with milk:plasma ratio approximately 2.4. Potential for serious adverse reactions in nursing infants; decision to discontinue nursing or drug should consider importance of drug to mother. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate studies in pregnant women. In animal studies, cinacalcet produced fetal toxicity (reduced fetal weight, increased incidence of skeletal variations) at doses 0.5-4 times the maximum human dose. Risk cannot be ruled out. Use only if potential benefit justifies potential risk to fetus. |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
["Hypocalcemia","Known hypersensitivity to cinacalcet or any component of the formulation"]
| Precautions | ["Hypocalcemia: Can cause life-threatening hypocalcemia; monitor serum calcium levels frequently.","Seizures: Increased risk, especially in patients with history of seizure disorder.","QT interval prolongation: Hypocalcemia may exacerbate QT prolongation; monitor ECGs in patients with risk factors.","Hypotension and worsening heart failure: Cases reported, especially in patients with impaired cardiac function.","Adynamic bone disease: May develop with oversuppression of PTH; monitor bone-specific alkaline phosphatase."] |
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| Fetal Monitoring | Monitor serum calcium levels closely during pregnancy, especially for hypocalcemia. Assess fetal growth via ultrasound if prolonged use. Monitor maternal blood pressure and renal function as indicated. |
| Fertility Effects | No formal fertility studies in humans. In animal studies, no impairment of fertility was observed at clinically relevant doses. |