Sensipar
Sensipar - General Information
Sensipar (INN) is a drug that acts as a calcimimetic (i.e. it mimics the action of calcium on tissues) by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe. Sensipar is used to treat hyperparathyroidism (elevated parathyroid hormone levels), a consequence of parathyroid tumors and chronic renal failure.
Pharmacology of Sensipar
Sensipar 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. Sensipar reduces calcium levels by increasing the sensitivity of the calcium sensing receptor to extracellular calcium.
Sensipar for patients
It is recommended that Sensipar be taken with food or shortly after a meal. Tablets should be taken whole and should not be divided.
Sensipar 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).
Sensipar Contraindications
Sensipar is contraindicated in patients with hypersensitivity to any component(s) of this product.
Additional information about Sensipar
Sensipar Indication: 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.
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. Sensipar 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.
Drug Interactions: Erythromycin This macrolide increases the serum levels and toxicity of cinacalcet
Itraconazole The imidazole increases the effect and toxicity of cinacalcet
Ketoconazole The imidazole increases the effect and toxicity of cinacalcet
Food Interactions: Take with food or soon after a meal.
Food markedly increases product bioavailability.
Peak levels and area under curve (drug exposure) are increased (82% and 68% respectively) when product is taken with a lipid-rich meal.
Generic Name: Cinacalcet
Synonyms: Not Available
Drug Category: Calcimimetics
Drug Type: Small Molecule; Approved
Other Brand Names containing Cinacalcet: Sensipar;
Absorption: Rapidly absorbed following oral administration.
Toxicity (Overdose): Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis. Overdosage of cinacalcet may lead to hypocalcemia.
Protein Binding: Approximately 93 to 97% bound to plasma proteins.
Biotransformation: 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.
Half Life: Terminal half-life is 30 to 40 hours. The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.
Dosage Forms of Sensipar: Tablet Oral
Chemical IUPAC Name: N-[(1R)-1-naphthalen-1-ylethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine
Chemical Formula: C22H22F3N
Cinacalcet on Wikipedia: https://en.wikipedia.org/wiki/Cinacalcet
Organisms Affected: Humans and other mammals
