CINACARE

Cinacalcet is a calcimimetic sold by Amgen under the trade name Sensipar® in North America and Australia and as Mimpara® in Europe.

It is used to treat hyperparathyroidism due to parathyroid tumours or renal failure.

For the treatment of secondary hyperparathyroidism in patients with Chronic Kidney Disease who are on hemodialysis or peritoneal dialysis.

Also for the treatment of hypercalcemia in patients with parathyroid carcinoma.

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.

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.

Rapidly absorbed following oral administration.

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.

Hover over products below to view reaction partners Cinacalcet Hydrocinnamic acid hydroxy-hydrocinnamic acid.

Cinacalcet is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6 and CYP1A2.

Renal excretion of metabolites was the primary route of elimination of radioactivity.

Terminal half-life is 30-40 hours.

The mean half-life of cinacalcet is prolonged by 33% and 70% in patients with moderate and severe hepatic impairment, respectively.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

Doses titrated up to 300 mg once daily have been safely administered to patients on dialysis.

Overdosage of cinacalcet may lead to hypocalcemia.

Cinacalcet tablets treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range.

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 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.

Titrate dose every to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg three or four times daily as necessary to normalize serum calcium levels.

Once the maintenance dose has been established, monitor serum calcium approximately monthly for patients with secondary HPT and every 2 months for patients with PC or primary HPT 2.1 Administration Cinacalcet tablets should be taken with food or shortly after a meal.

Cinacalcet tablets are administered orally and should always be taken whole and not chewed, crushed, or divided. 2.2 Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis The recommended starting oral dose of cinacalcet tablets is 30 mg once daily.

Serum calcium and serum phosphorus should be measured within 1 week and intact parathyroid hormone (iPTH) should be measured to 4 weeks after initiation or dose adjustment of cinacalcet tablets.

Cinacalcet tablets should be titrated no more frequently than every to 4 weeks through sequential doses of 30, 60, 90, 120, and 180 mg once daily to target iPTH levels of to 300 pg/mL.

Serum iPTH levels should be assessed no earlier than 12 hours after dosing with cinacalcet tablets.

Cinacalcet tablets can be used alone or in combination with vitamin D sterols and/or phosphate binders.

During dose titration, serum calcium levels should be monitored frequently and if levels decrease below the normal range, appropriate steps should be taken to increase serum calcium levels, such as by providing supplemental calcium, initiating or increasing the dose of calcium-based phosphate binder, initiating or increasing the dose of vitamin D sterols, or temporarily withholding treatment with cinacalcet tablets. 2.3 Patients with Parathyroid Carcinoma and Primary Hyperparathyroidism The recommended starting oral dose of cinacalcet tablet is 30 mg twice daily.

The dose of cinacalcet tablets should be titrated every to 4 weeks through sequential doses of 30 mg twice daily, 60 mg twice daily, and 90 mg twice daily, and 90 mg 3 or 4 times daily as necessary to normalize serum calcium levels.

Serum calcium should be measured within 1 week after initiation or dose adjustment of cinacalcet tablets. 2.4 Switching from Parsabiv (etelcalcetide) to Cinacalcet Discontinue etelcalcetide for at least 4 weeks prior to starting Cinacalcet.

Ensure corrected serum calcium is at or above the lower limit of normal prior to Cinacalcet initiation.

Cinacalcet treatment at a starting dose of 30 mg once daily. 2.5 Monitoring for Hypocalcemia Once the maintenance dose has been established, serum calcium should be measured approximately monthly for patients with secondary hyperparathyroidism with CKD on dialysis, and every 2 months for patients with parathyroid carcinoma or primary hyperparathyroidism.

For secondary hyperparathyroidism patients with

CKD on dialysis, if serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, calcium-containing phosphate binders and/or vitamin D sterols can be used to raise serum calcium.

If serum calcium falls below 7.5 mg/dL, or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased, withhold administration of cinacalcet tablets until serum calcium levels reach 8.0 mg/dL and/or symptoms of hypocalcemia have resolved.

Treatment should be reinitiated using the next lowest dose of cinacalcet tablets.

Cinacalcet 30 mg tablets are formulated as light-green, film-coated, oval-shaped, biconvex tablets debossed with "CL" on one side and "410" on the opposite side, packaged in bottles of 30 tablets. (NDC 69097-410-02).

Cinacalcet 60 mg tablets are formulated as light-green, film-coated, oval-shaped, biconvex tablets debossed with "CL" on one side and "411" on the opposite side, packaged in bottles of 30 tablets. (NDC 69097-411-02).

Cinacalcet 90 mg tablets are formulated as light-green, film-coated, oval-shaped, biconvex tablets debossed with "CL" on one side and "412" on the opposite side, packaged in bottles of 30 tablets. (NDC 69097-412-02).

Store at 25 °C (77 °F), excursions permitted from 15 °C to 30 °C (59°F to 86°F). .

The safety and efficacy of cinacalcet tablets have not been established in pediatric patients.

The use of Cinacalcet for the treatment of secondary HPT in pediatric patients with CKD on dialysis was evaluated in two randomized, controlled studies (Pediatric Study and Study 2) where 47 pediatric patients aged 6 years to less than 18 years received at least one dose of Cinacalcet and in one single-arm study (Pediatric Study 3) where 17 pediatric patients aged 28 days to less than 6 years received at least one dose of Cinacalcet.

Dosing with cinacalcet in a Pediatric

Study was stopped because of a fatality in a cinacalcet-treated individual.

The individual was noted to be severely hypocalcemic at the time of death.

The cause of death was multifactorial and a contribution of cinacalcet to the death could not be excluded.

Study was terminated and changes to

Cinacalcet dosing after the fatality were implemented in Pediatric Study and Study to minimize the risk of severe hypocalcemia.

The data in Pediatric

Studies and 3 were insufficient to establish the safety and efficacy of Cinacalcet for the treatment of secondary HPT in pediatric patients with CKD on dialysis.

In aggregate, the pediatric studies did not establish a safe and effective Cinacalcet dosing regimen for the pediatric population.

Of the total number of subjects (n=1136) in clinical studies of cinacalcet tablets, 26 percent were and over, and 9 percent were and over.

No overall differences in the safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.