Cinacalcet

What it is and how it works

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.

Indications

Cinacalcet tablet is a positive modulator of the calcium sensing receptor indicated for: • Secondary Hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis. 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). • 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. Secondary Hyperparathyroidism Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis . Limitations of Use: Cinacalcet tablets are not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia . Parathyroid Carcinoma Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma .

Dosage and administration (summary)

Cinacalcet tablets should be taken with food or shortly after a meal Tablets should always be taken whole and not divided Secondary HPT in patients with CKD on dialysis : 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. Hypercalcemia in patients with PC or hypercalcemia in patients with primary HPT : Starting dose is 30 mg twice daily.

Contraindications

Cinacalcet treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range . Cinacalcet treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. ( 4, 5.1 )

Warnings and precautions

• Hypocalcemia : Life threatening events and fatal outcomes were reported. Hypocalcemia can prolong QT interval, lower the threshold for seizures, and cause hypotension, worsening heart failure, and/or arrhythmia. Monitor serum calcium carefully for the occurrence of hypocalcemia during treatment. ( 2.4 , 5.1 ) • Upper Gastrointestinal (GI) Bleeding : Patients with risk factors for upper GI bleeding may be at increased risk. Monitor patients and promptly evaluate and treat any suspected GI bleeding.

Pregnancy

Pregnancy Risk Summary Limited case reports of cinacalcet use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, when female rats were exposed to cinacalcet during the period of organogenesis through to weaning at 2 to 3 times the systemic drug levels (based on AUC)…

Storage and supply

Cinacalcet tablets, 30 mg are formulated as light-green, oval-shaped, film-coated tablets debossed “C” on one side and “30” on the other side, packaged in bottles of 30 and 500 tablets.

Source: Cinacalcet (Cinacalcet) — US FDA prescribing information, 2024-04-05, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.