Cinacalcet (cinacalcet HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Cinacalcet hydrochloride, a calcimimetic agent, binds to and increases sensitivity of calcium-sensing receptors on the parathyroid glands to extracellular calcium, which results in reduced parathyroid hormone (PTH, parathormone) concentrations and concomitant decreases in serum calcium concentrations.
Cinacalcet, a phenylethylamine calcimimetic agent, binds to and allosterically modulates calcium-sensing receptors located on the parathyroid glands to increase their sensitivity to activation by extracellular calcium, thereby inhibiting parathyroid hormone (PTH, parathormone) secretion and lowering serum PTH concentrations within a few hours after oral administration. The reduction in intact PTH (iPTH) concentrations in patients with chronic renal disease is correlated with plasma cinacalcet concentrations. In dialysis patients with secondary hyperparathyroidism, serum calcium and phosphorus concentrations usually decline as PTH concentrations decrease.
Reductions in PTH concentration in dialysis patients with uncontrolled secondary hyperparathyroidism are associated with a decrease in bone turnover and bone fibrosis. Calcium-sensing receptors located on the surface of chief cells of the parathyroid glands are the principal regulators of PTH secretion.
Following oral administration of cinacalcet, peak plasma concentrations of the drug are reached in approximately 2-6 hours. Peak plasma concentrations and systemic exposure are proportional to dose over the dosage range of 30-180 mg once daily. With once-daily dosing, the mean accumulation ratio is approximately 2.
Administration with a high-fat or low-fat meal increases peak plasma concentrations of the drug by 82 or 65%, respectively, and increases systemic exposure by 68 or 50%, respectively, compared with administration in the fasting state. Cinacalcet is approximately 93-97% bound to plasma proteins. Cinacalcet is metabolized by multiple enzymes, mainly cytochrome P-450 (CYP) isoenzymes 3A4, 2D6, and 1A2, and is a potent inhibitor of CYP2D6 in vitro.
The drug has a terminal half-life of 30-40 hours and is eliminated in urine (80%, mainly as metabolites) and to a lesser extent in feces (15%).
Cinacalcet hydrochloride is used for the treatment of secondary hyperparathyroidism associated with chronic renal disease in patients who are undergoing hemodialysis or peritoneal dialysis, the treatment of hypercalcemia associated with parathyroid carcinoma, and the treatment of hypercalcemia associated with primary hyperparathyroidism in patients who would be candidates for parathyroidectomy based on serum calcium concentrations but who are unable to undergo the surgery.
Generic name: cinacalcet HCl
Pronunciation: (SIN-a-KAL-set)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Cinacalcet
Indications
The following indications are listed for Cinacalcet:
- Hypercalcemia Due To Primary Hyperparathyroidism
- Hyperparathyroidism Secondary To Chronic Renal Failure With Dialysis
- Parathyroid Carcinoma With Hypercalcemia
Also known as: Hyperparathyroidism Associated With Dialysis Dependent Renal Failure, Pth-Mediated Hypercalcemia.
Dosing
Dosage of cinacalcet hydrochloride is expressed in terms of cinacalcet. Dosage of the drug must be individualized.
Because severe or prolonged nausea and vomiting can result in dehydration and worsening hypercalcemia, careful monitoring of electrolytes is recommended in patients with these adverse effects.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Cinacalcet is metabolized by cytochrome P-450 (CYP) isoenzymes 1A2, 2D6, and 3A4. In vitro studies indicate that cinacalcet is a potent inhibitor of CYP2D6, but cinacalcet does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, or 3A4 nor does it induce CYP isoenzymes.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Cinacalcet is contraindicated in patients with serum calcium concentrations below the lower limit of normal.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most commonly reported adverse effects of cinacalcet in patients with hypercalcemia associated with parathyroid carcinoma or primary hyperparathyroidism or in dialysis patients with secondary hyperparathyroidism are nausea and vomiting.
In 3 controlled studies in dialysis patients with secondary hyperparathyroidism, adverse effects occurring in 5% of more of patients receiving cinacalcet for up to 6 months and at an incidence higher than that reported with placebo included nausea, vomiting, diarrhea, myalgia, dizziness, hypertension, asthenia, anorexia, noncardiac chest pain, and access infection. In the EVOLVE study in dialysis patients with secondary hyperparathyroidism, adverse effects reported in 5% or more of patients receiving cinacalcet for up to 64 months and at an incidence higher than that reported with placebo included nausea, vomiting, diarrhea, dyspnea, cough, hypotension, headache, hypocalcemia, muscle spasms, abdominal pain (including upper abdominal pain), hyperkalemia, upper respiratory tract infection, dyspepsia, dizziness, decreased appetite, asthenia, and constipation.
Adverse effects in patients with hypercalcemia associated with parathyroid carcinoma or primary hyperparathyroidism generally are similar to those observed in dialysis patients.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of cinacalcet in pediatric patients younger than 18 years of age have not been established, and the drug is not indicated for use in pediatric patients. In 2013, FDA announced suspension of pediatric clinical trials of the drug after the death of a 14-year-old adolescent with severe hypocalcemia occurred during a trial.
Category C. (See Users Guide.) Women who become pregnant while receiving cinacalcet are encouraged to enroll in the manufacturer's pregnancy surveillance program. Patients or their clinicians should call 800-772-6436 to enroll.
Cinacalcet is distributed into milk in rats; it is not known whether cinacalcet is distributed into human milk. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman. Women who opt to continue cinacalcet treatment while nursing are encouraged to enroll in the manufacturer's lactation surveillance program. Patients or their clinicians should call 800-772-6436 to enroll.
No substantial differences in the pharmacokinetic profile, safety, and efficacy of cinacalcet have been observed in patients 65 years of age or older relative to younger adults. However, greater sensitivity of some older patients cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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