DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Active ingredient: Cinacalcet - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Calcimimetics

Dosage Forms

  • Tablets (light-green, film-coated, oval-shaped tablets for oral administration in strengths of 30 mg, 60 mg, and 90 mg)

Brands / Synonyms

Sensipar; Sensipar

Indications

For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease on dialysis. Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.

Pharmacology

Cinacalcet is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues). Secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) is a progressive disease, associated with increases in parathyroid hormone (PTH) levels and derangements in calcium and phosphorus metabolism. Increased PTH stimulates osteoclastic activity resulting in cortical bone resorption and marrow fibrosis. The goals of treatment of secondary hyperparathyroidism are to lower levels of PTH, calcium, and phosphorus in the blood, in order to prevent progressive bone disease and the systemic consequences of disordered mineral metabolism. In CKD patients on dialysis with uncontrolled secondary HPT, reductions in PTH are associated with a favorable impact on bone-specific alkaline phosphatase (BALP), bone turnover and bone fibrosis. Cinacalcet reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.

Mechanism of Action

The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of parathyroid hormone secretion. Cinacalcet directly lowers parathyroid hormone levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium. The reduction in parathyroid hormone is associated with a concomitant decrease in serum calcium levels.

Absorption

Rapidly absorbed following oral administration.

Toxicity

Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of cinacalcet may lead to hypocalcemia.

Biotrnasformation / Drug Metabolism

Metabolism is hepatic by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2. After administration of a 75 mg radiolabeled dose to healthy volunteers, cinacalcet was rapidly and extensively metabolized via: 1) oxidative N-dealkylation to hydrocinnamic acid and hydroxy-hydrocinnamic acid, which are further metabolized via ß-oxidation and glycine conjugation; the oxidative N-dealkylation process also generates metabolites that contain the naphthalene ring; and 2) oxidation of the naphthalene ring on the parent drug to form dihydrodiols, which are further conjugated with glucuronic acid.

Contraindications

Sensipar is contraindicated in patients with hypersensitivity to any component(s) of this product.

Drug Interactions

and/or Drug/Laboratory Test Interactions

See CLINICAL PHARMACOLOGY, Pharmacokinetics and Drug Interactions.

Effect of Sensipar on other drugs:

Drugs metabolized by cytochrome P450 2D6 (CYP2D6): Sensipar™ is a strong in vitro inhibitor of CYP2D6. Therefore, dose adjustments of concomitant medications that are predominantly metabolized by CYP2D6 and have a narrow therapeutic index (e.g., flecainide, vinblastine, thioridazine and most tricyclic antidepressants) may be required.

Amitriptyline: Concurrent administration of 25 mg or 100 mg cinacalcet with 50 mg amitriptyline increased amitriptyline exposure and nortriptyline (active metabolite) exposure by approximately 20% in CYP2D6 extensive metabolizers.

Effect of other drugs on Sensipar :

Sensipar™ is metabolized by multiple cytochrome P450 enzymes, primarily CYP3A4, CYP2D6, and CYP1A2.

Ketoconazole: Sensipar is metabolized in part by CYP3A4. Co-administration of ketoconazole, a strong inhibitor of CYP3A4, increased cinacalcet exposure following a single 90 mg dose of Sensipar by 2.3 fold. Dose adjustment of Sensipar may be required and PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g., ketoconazole, erythromycin, itraconazole; see DOSAGE AND ADMINISTRATION).

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017