Cinacalcet
Cinacalcet Prescribing Information
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. (
Cinacalcet tablets are indicated for the treatment of secondary hyperparathyroidism (HPT) in adult patients with chronic kidney disease (CKD) on dialysis
Cinacalcet tablets are not indicated for use in patients with CKD who are not on dialysis because of an increased risk of hypocalcemia
• Hypercalcemia in adult patients with Parathyroid Carcinoma (PC). (
Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma
• Severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy. (
Cinacalcet tablets are indicated for the treatment of severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy
• Cinacalcet tablets should be taken with food or shortly after a meal (
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.
• Tablets should always be taken whole and not divided (
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.
• Secondary HPT in patients with CKD 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 1 to 4 weeks after initiation or dose adjustment of 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
o Starting dose is 30 mg once daily.
o 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.
o iPTH levels should be measured no earlier than 12 hours after most recent dose.
• Hypercalcemia in patients with PC or severe hypercalcemia in patients with primary HPT (
The recommended starting oral dose of cinacalcet tablets is 30 mg twice daily.
The dose of cinacalcet tablets should be titrated every 2 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
o Starting dose is 30 mg twice daily.
o Titrate dose every 2 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 (
Discontinue etelcalcetide for at least 4 weeks prior to starting cinacalcet tablets. Ensure corrected serum calcium is at or above the lower limit of normal prior to cinacalcet tablets initiation
Cinacalcet tablets, 30 mg are light green, oval, biconvex, film coated, tablets debossed with ‘H’ on one side and ‘C6’ on the other side.
Cinacalcet tablets, 60 mg are light green, oval, biconvex, film coated, tablets debossed with ‘H’ on one side and ‘C7’ on the other side.
Cinacalcet tablets, 90 mg are light green, oval, biconvex, film coated, tablets debossed with ‘H’ on one side and ‘C8’ on the other side.
• Pediatric Use: A fatal outcome was reported in a pediatric clinical trial patient with severe hypocalcemia. Cinacalcet is not indicated for use in pediatric patients. (
The safety and efficacy of cinacalcet 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 1 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 Pediatric Study 1 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
Cinacalcet tablets treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range
Cinacalcet lowers serum calcium and can lead to hypocalcemia
Cinacalcet is not indicated for patients with CKD not on dialysis
Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with cinacalcet. Patients with congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to cinacalcet. Closely monitor corrected serum calcium and QT interval in patients at risk receiving cinacalcet.
In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3,049) of cinacalcet-treated patients and 0.7% (5/687) of placebo-treated patients. While the basis for the reported difference in seizure rate is not clear, the threshold for seizures is lowered by significant reductions in serum calcium levels. Monitor serum calcium levels in patients with seizure disorders receiving cinacalcet.
Concurrent administration of cinacalcet with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia. Closely monitor serum calcium in patients receiving cinacalcet and concomitant therapies known to lower serum calcium levels.
Educate patients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur. If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration). Cinacalcet dose reduction or discontinuation of cinacalcet may be necessary
•
Discontinue etelcalcetide for at least 4 weeks prior to starting cinacalcet tablets. Ensure corrected serum calcium is at or above the lower limit of normal prior to cinacalcet tablets initiation
Cinacalcet lowers serum calcium and can lead to hypocalcemia
Cinacalcet is not indicated for patients with CKD not on dialysis
Decreases in serum calcium can also prolong the QT interval, potentially resulting in ventricular arrhythmia. Cases of QT prolongation and ventricular arrhythmia have been reported in patients treated with cinacalcet. Patients with congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia may be at increased risk for QT interval prolongation and ventricular arrhythmias if they develop hypocalcemia due to cinacalcet. Closely monitor corrected serum calcium and QT interval in patients at risk receiving cinacalcet.
In clinical studies, seizures (primarily generalized or tonic-clonic) were observed in 1.4% (43/3,049) of cinacalcet-treated patients and 0.7% (5/687) of placebo-treated patients. While the basis for the reported difference in seizure rate is not clear, the threshold for seizures is lowered by significant reductions in serum calcium levels. Monitor serum calcium levels in patients with seizure disorders receiving cinacalcet.
Concurrent administration of cinacalcet with calcium-lowering drugs including other calcium-sensing receptor agonists could result in severe hypocalcemia. Closely monitor serum calcium in patients receiving cinacalcet and concomitant therapies known to lower serum calcium levels.
Educate patients on the symptoms of hypocalcemia and advise them to contact a healthcare provider if they occur. If corrected serum calcium falls below the lower limit of normal or symptoms of hypocalcemia develop, start or increase calcium supplementation (including calcium, calcium-containing phosphate binders, and/or vitamin D sterols or increases in dialysate calcium concentration). Cinacalcet dose reduction or discontinuation of cinacalcet may be necessary
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Cases of gastrointestinal bleeding, mostly upper gastrointestinal bleeding, have occurred in patients using calcimimetics, including cinacalcet, from postmarketing and clinical trial sources. The exact cause of GI bleeding in these patients is unknown.
Patients with risk factors for upper GI bleeding (such as known gastritis, esophagitis, ulcers or severe vomiting) may be at increased risk for GI bleeding when receiving cinacalcet treatment. Monitor patients for worsening of common GI adverse reactions of nausea and vomiting associated with cinacalcet
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In postmarketing safety surveillance, isolated, idiosyncratic cases of hypotension, worsening heart failure, and/or arrhythmia have been reported in patients with impaired cardiac function, in which a causal relationship to cinacalcet could not be completely excluded and which may be mediated by reductions in serum calcium levels
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Adynamic bone disease may develop if iPTH levels are suppressed below 100 pg/mL. One clinical study evaluated bone histomorphometry in patients treated with cinacalcet for 1 year. Three patients with mild hyperparathyroid bone disease at the beginning of the study developed adynamic bone disease during treatment with cinacalcet. Two of these patients had iPTH levels below 100 pg/mL at multiple time points during the study. In three 6-month, phase 3 studies conducted in patients with CKD on dialysis, 11% of patients treated with cinacalcet had mean iPTH values below 100 pg/mL during the efficacy-assessment phase. If iPTH levels decrease below 150 pg/mL in patients treated with cinacalcet, the dose of cinacalcet and/or vitamin D sterols should be reduced or therapy discontinued.