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Pronunciation: SIN-a-KAL-set HYE-droe-KLOR-ide
- Tablets, oral 30 mg
- Tablets, oral 60 mg
- Tablets, oral 90 mg
Lowers parathyroid hormone (PTH) levels by increasing sensitivity of the calcium-sensing receptor to extracellular calcium.
T max is approximately 2 to 6 h. Steady state is achieved within 7 days. The C max and AUC (0-inf) were increased 82% and 68%, respectively, when cinacalcet was administered with a high-fat meal compared with fasting. The C max and AUC (0-inf) of cinacalcet were increased 65% and 50%, respectively, when cinacalcet was administered with a low-fat meal compared with fasting.
Vd is approximately 1,000 L. Protein binding is 93% to 97%.
Metabolized by CYP3A4, CYP2D6, and CYP1A2.
Terminal half-life is 30 to 40 h. Approximately 80% of a dose is recovered in the urine and 15% in the feces.
Special PopulationsRenal Function Impairment
Pharmacokinetics in patients with mild, moderate, or severe renal impairment and those on hemodialysis or peritoneal dialysis are comparable with healthy volunteers.Hepatic Function Impairment
In patients with moderate or severe hepatic impairment, the AUCs were 2.4 and 4.2 times higher, respectively, than in healthy subjects; the half-life is increased from 49 h in healthy subjects to 65 h and 84 h in patients with moderate and severe hepatic impairment, respectively.Elderly
Pharmacokinetics are similar in patients 65 y and older compared with patients younger than 65 y.Children
The pharmacokinetics have not been studied in patients younger than 18 y.
Indications and Usage
Treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis; hypercalcemia in patients with parathyroid carcinoma; for the treatment of severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy.
Dosage and AdministrationHypercalcemia in Parathyroid Carcinoma and Primary Hyperparathyroidism
PO Start with 30 mg twice daily. Titrate every 2 to 4 wk through sequential doses of 30, 60, and 90 mg twice daily, and 90 mg 3 or 4 times daily as needed to normalize serum calcium levels.Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease on Dialysis
PO Start with 30 mg daily. Titrate dose every 2 to 4 wk through sequential doses of 30, 60, 90, 120, and 180 mg daily based on target intact PTH levels of 150 to 300 pg/mL.
- Can be used alone or in combination with vitamin D and/or phosphate binders.
- Administer with food or shortly after a meal. Swallow tablets whole and do not crush, chew, or divide.
- Serum intact PTH levels should be assessed no earlier than 12 h after dosing.
Store between 59° and 86°F.
Drug InteractionsDrugs metabolized by CYP2D6 (eg, carvedilol, flecainide, metoprolol, thioridazine, most tricyclic antidepressants [eg, amitriptyline, desipramine])
Plasma concentrations of these agents may be elevated, increasing the pharmacologic effects and adverse reactions. Dosage adjustments may be needed, especially in agents with a narrow therapeutic index.Strong inhibitors of CYP3A4 (eg, erythromycin, itraconazole, ketoconazole)
Cinacalcet concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Closely monitor patients and adjust the cinacalcet dose as needed.
Hypertension (7%); arrhythmia, idiosyncratic hypotension, worsening heart failure (postmarketing).
Paresthesia (29%); fatigue, headache (21%); depression (18%); asthenia (17%); dizziness (10%).
Nausea (66%); vomiting (52%); diarrhea (21%); constipation (18%).
Hypersensitivity reactions, including angioedmea and urticaria (postmarketing).
Dehydration (24%); anorexia, hypercalcemia (21%).
Fracture (21%); arthralgia (17%); myalgia (15%); limb pain (12%).
Anemia (17%); upper respiratory infection (12%); noncardiac chest pain (6%); access infection (5%); rash (postmarketing).
Carefully monitor patient for signs and symptoms of hypocalcemia (eg, convulsions, cramping, myalgia, paresthesias, tetany). Measure serum calcium and serum phosphorus within 1 wk and measure intact PTH 1 to 4 wk after initiating or adjusting the dose of cinacalcet. Once a maintenance dose is established, measure serum calcium and serum phosphorus monthly, and intact PTH every 1 to 3 mo; in parathyroid carcinoma patients, once the maintenance dose level has been established, measure serum calcium every 2 mo. Closely monitor intact PTH, serum phosphorus, and serum calcium concentrations throughout treatment in patients with moderate or severe hepatic impairment.
Category C .
Safety and efficacy not established.
Use with caution in patients with moderate to severe hepatic impairment.
Adynamic bone disease
May occur if intact PTH levels are suppressed below 100 pg/mL. Ensure that the dose of cinacalcet and/or vitamin D is reduced if intact PTH levels decrease to less than 150 pg/mL.
During postmarketing experience, idiosyncratic cases of arrhythmia, hypotension, and/or worsening of heart failure have been reported in patients with impaired cardiac function.
May occur; closely monitor. Do not initiate treatment if serum calcium is less than the lower limit of the normal range. If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, use calcium-containing phosphate binders and/or vitamin D sterols to raise serum calcium. Ensure that cinacalcet is temporarily discontinued in patients whose serum calcium falls below 7.5 mg/dL or if symptoms of hypocalcemia persist and the dose of vitamin D cannot be increased. Therapy can be reinstituted using the next lowest dose when serum calcium level reaches 8 mg/dL and/or symptoms of hypocalcemia have resolved.
Seizures may occur. Closely monitor serum calcium levels, particularly in patients with a history of seizures.
- Advise patient to take prescribed dose with food or shortly after a meal. Caution patient to swallow tablets whole and not to chew, divide, or crush.
- Caution patient not to change or stop taking the dose unless advised by health care provider.
- Instruct patient to continue taking other medications (eg, vitamin D and/or phosphate binders) as prescribed by health care provider for controlling calcium levels.
- Instruct patient to immediately inform health care provider if the following signs or symptoms of hypocalcemia develop: abnormal skin sensations, muscle aches, muscle cramping or spasm, seizure activity.
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