CINACALCET HYDROCHLORIDE
Clinical safety rating
cautionAnimal 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. |
| Molecular Weight | 357.85 |
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 | No adequate studies in pregnant women; animal studies show fetal harm at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | No adequate studies in pregnant women; consider maternal hyperparathyroidism risks if untreated. |
| 3rd trimester | No adequate studies in pregnant women; may cause fetal hypocalcemia if used near term. |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause hypocalcemia monitor serum calcium levels closely.
| Placental transfer | Crosses placenta in animal studies; degree in humans unknown but likely due to low molecular weight. |
| Breastfeeding | Excreted in rat milk; unknown in humans. Caution advised due to potential for hypocalcemia in infant. |
| Lactation Rating | L3 (Moderately Safe) - limited data; risk of hypocalcemia. |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Common Effects | Nausea |
| Serious Effects |
Hypocalcemia
| 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. |
| Food/Dietary | Take with food or immediately after a dialysis treatment. Avoid high-calcium meals (e.g., dairy) within 2 hours of dosing as calcium binds cinacalcet and reduces absorption. No other dietary restrictions; maintain consistent calcium intake per renal diet. |
| Clinical Pearls | Monitor serum calcium within 1 week of initiation or dose adjustment; cinacalcet may cause hypocalcemia, so do not start if calcium <8.4 mg/dL. Correct elevated PTH in CKD patients with iPTH >300 pg/mL on dialysis; not for use in non-dialysis CKD. QTc prolongation risk: obtain baseline ECG and monitor electrolytes, especially if on QT-prolonging drugs. Nausea and vomiting are common; administer with food or after dialysis session to improve tolerance. |
| Patient Advice | Take cinacalcet with food or right after a dialysis session to reduce stomach upset. · Do not stop taking this medication suddenly; consult your doctor if you have side effects. · Report symptoms of low calcium such as muscle cramps, numbness, or tingling in fingers/toes. · Tell your doctor if you have a history of seizures or liver problems. · Avoid taking strong CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) unless prescribed; inform all healthcare providers. |
Loading safety data…