SENSIPAR
Clinical safety rating
cautionComprehensive clinical and safety monograph for SENSIPAR (SENSIPAR).
Calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR) on parathyroid chief cells, increasing its sensitivity to extracellular calcium, thereby reducing parathyroid hormone (PTH) secretion.
| Metabolism | Hepatic via CYP3A4, CYP2D6, CYP1A2; major metabolites are inactive. |
| Excretion | Renal excretion of unchanged drug and metabolites accounts for approximately 84% of the administered dose; fecal excretion accounts for approximately 11%. The primary metabolic pathway is CYP3A4-mediated oxidation, followed by glucuronidation. |
| Half-life | The terminal elimination half-life of cinacalcet is approximately 30 to 40 hours in patients with normal renal function, supporting once-daily dosing. Steady-state concentrations are achieved within 7 days. |
| Protein binding | Cinacalcet is approximately 93 to 97% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The volume of distribution is approximately 1000 L (about 14 L/kg in a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 20 to 25% due to first-pass metabolism; administration with food increases bioavailability by approximately 50% compared to fasting. |
| Onset of Action | Oral administration: Reduction in serum parathyroid hormone (PTH) levels is observed within 1 to 2 hours post-dose. |
| Duration of Action | The duration of PTH suppression is approximately 8 to 12 hours after a single dose; however, with once-daily dosing, sustained reduction in PTH and serum calcium is maintained throughout the dosing interval. |
| Molecular Weight | 560.83 |
30 mg orally once daily, titrated every 2-4 weeks to a maximum of 180 mg once daily to achieve target iPTH reduction.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >= 30 mL/min). Not recommended for patients with severe renal impairment (CrCl < 30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh Class A or B). Use with caution in severe hepatic impairment (Child-Pugh Class C) with no specific dose recommendations. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment; dosing should be based on renal function. Elderly patients may have decreased renal function; monitor serum calcium and iPTH levels closely. |
| 1st trimester | No adequate studies in pregnant women; animal studies show fetal harm at high doses. Use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | Same as T1; limited human data. Consider maternal benefit versus fetal risk. |
| 3rd trimester | Same as T1; may cause fetal hypocalcemia due to maternal calcimimetic effects. Avoid unless absolutely necessary. |
Clinical note
Comprehensive clinical and safety monograph for SENSIPAR (SENSIPAR).
| Placental transfer | Expected to cross the placenta based on molecular weight and animal studies; human data limited. |
| Breastfeeding | Excreted in animal milk; unknown in humans. Due to risk of serious adverse reactions in nursing infants (e.g., hypocalcemia), decide to discontinue nursing or the drug, taking into account importance of drug to mother. |
| Lactation Rating | L4 (possibly hazardous) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show fetal harm at high doses (reduced fetal weight, skeletal variations). Second/third trimester: No adequate human studies; potential fetal/neonatal hypocalcemia due to maternal calcium-sensing receptor modulation. Risk cannot be excluded. |
| Fetal Monitoring | Monitor serum calcium (corrected for albumin) at baseline and regularly throughout pregnancy; monitor fetal growth and development via ultrasound. Monitor neonate for hypocalcemia, including jitteriness, tetany, or seizures. |
| Fertility Effects | No human data on fertility. Animal studies show no impairment of fertility at up to 0.65 times the human exposure (based on AUC). |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypocalcemia
| Precautions | Hypocalcemia: monitor serum calcium, especially during initiation and dose titration, Seizures: risk due to hypocalcemia, QT prolongation: caution in patients with history of QT interval prolongation or on concurrent QT-prolonging drugs, Hypotension: possible during dialysis use, Adynamic bone disease: potential with oversuppression of PTH |
| Food/Dietary | SENSIPAR should be taken with food or shortly after a meal to enhance absorption. No specific foods are contraindicated, but avoid high-calcium meals immediately before or after dosing as they may reduce absorption. Grapefruit and grapefruit juice may increase cinacalcet levels; avoid concurrent use. |
| Clinical Pearls | SENSIPAR (cinacalcet) is a calcimimetic used for secondary hyperparathyroidism in CKD on dialysis and for hypercalcemia in parathyroid carcinoma. Monitor serum calcium closely; hypocalcemia is a common adverse effect. Do not initiate if serum calcium is below the lower limit of normal. Administer with food or shortly after a meal to increase absorption. Dose adjustments may be needed with moderate to severe hepatic impairment. |
| Patient Advice | Take this medication with food or right after a meal. · Do not split, crush, or chew tablets; swallow whole. · Report symptoms of low calcium: muscle cramps, numbness, tingling, or seizures. · Keep all lab appointments for calcium and PTH monitoring. · Avoid taking with other medications without consulting your doctor; some may interact. |
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