Overview
11 DESCRIPTION Cinacalcet tablets contain the hydrochloride salt of cinacalcet, a positive modulator of the calcium sensing receptor. The empirical formula for cinacalcet is C 22 H 22 F 3 N⋅HCl with a molecular weight of 393.9 g/mol (hydrochloride salt) and 357.4 g/mol (free base). It has one chiral center having an R-absolute configuration.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH synthesis and secretion. Cinacalcet, the active ingredient in cinacalcet tablets is a calcimimetic agent that directly lowers PTH levels by increasing the sensitivity of the calcium-sensing receptor to activation by extracellular calcium. The reduction in PTH is associated with a concomitant decrease in serum calcium levels. 12.2 Pharmacodynamics Reduction in iPTH levels correlated with the plasma cinacalcet concentrations in patients with CKD. The nadir in iPTH level occurs approximately 2 to 6 hours post dose, corresponding with the maximum plasma concentration (C max ) of cinacalcet.
Indications
- 1 INDICATIONS AND USAGE Cinacalcet is a positive modulator of the calcium sensing receptor indicated for: Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. ( 1.1 ) Limitations of Use : Cinacalcet tablets are not indicated for use in patients with CKD who are not on dialysis Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). ( 1.2 ) Hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy. ( 1.3 ) 1.
Common Doses
- 30 mg
- 180 mg
- 60 mg
- 90 mg
Dosage
2 DOSAGE AND ADMINISTRATION Cinacalcet tablets should be taken with food or shortly after a meal ( 2.1 ). Tablets should always be taken whole and not divided ( 2.1 ) Secondary HPT in patients with CKD on dialysis ( 2.2 ): Starting dose is 30 mg once daily. Titrate dose no more frequently than every 2 to 4 weeks through sequential doses of 30, 60, 90, 120, and 180 mg once daily as necessary to achieve targeted intact parathyroid hormone (iPTH) levels. iPTH levels should be measured no earlier than 12 hours after most recent dose.
Contraindications
- 4 CONTRAINDICATIONS Cinacalcet tablets treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range [see Warnings and Precautions ( 5.1 )]. Cinacalcet tablets treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. ( 4 , 5.1 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of labeling: Hypocalcemia [see Warnings and Precautions ( 5.1 )] Upper Gastrointestinal Bleeding [see Warnings and Precautions ( 5.2 )] Hypotension, Worsening Heart Failure and/or Arrhythmias [ see Warnings and Precautions ( 5.3 )] Adynamic Bone Disease [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (i.e., ≥ 25%) associated with cinacalcet were nausea and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Ltd.
Interactions
- 7 DRUG INTERACTIONS Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. Dose adjustment and monitoring of iPTH serum phosphorus and serum calcium may be required. ( 7.1 ) Cinacalcet is a strong inhibitor of CYP2D6. Dose adjustments may be required for concomitant medications that are predominantly metabolized by CYP2D6. ( 7.2 ) 7.1 Strong CYP3A4 Inhibitors Cinacalcet is partially metabolized by CYP3A4. Dose adjustment of cinacalcet tablets may be required if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor (e.g.