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Pronunciation
(sin a KAL cet)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis; treatment of hypercalcemia in patients with parathyroid carcinoma; treatment of severe hypercalcemia in patients with primary hyperparathyroidism who are unable to undergo parathyroidectomy
Pregnancy Risk Factor
C
Pregnancy Considerations
In animal studies, there were no teratogenic effects observed, although decreased pup weights were noted. There are no adequate or well-controlled studies in pregnant women. Use in pregnancy only if potential benefit to mother justifies risk to the fetus. Women who become pregnant during cinacalcet treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program (1-800-772-6436).
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Due to the potential for serious adverse effects in the nursing infant, the manufacturer recommends discontinuing nursing or discontinuing cinacalcet.
Contraindications
Hypocalcemia (serum calcium lower than the lower limit of normal range)
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Adynamic bone disease: May develop if intact parathyroid hormone (iPTH) levels are suppressed (<100 pg/mL); reduce dose or discontinue use of cinacalcet and/or vitamin D if iPTH levels decrease below 150-300 pg/mL (NKF-K/DOQI guidelines).
• Cardiovascular effects: Cases of idiosyncratic hypotension, worsening of heart failure, and/or arrhythmia have been reported in patients with impaired cardiovascular function; may correlate with decreased serum calcium.
• Hypocalcemia: Use is contraindicated in hypocalcemia. Monitor serum calcium and for symptoms of hypocalcemia (eg, cramps, myalgia, paresthesia, seizure, tetany). May require treatment interruption, dose reduction, or initiation (or dose increases) of calcium-based phosphate binder or vitamin D to raise serum calcium depending on calcium levels or symptoms of hypocalcemia.
• Testosterone level reductions: Cinacalcet may cause a decrease in testosterone levels (free and total). Although below normal testosterone levels may occur in patients with end-stage renal disease, the clinical significance has not been determined.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with moderate-to-severe hepatic impairment (Child-Pugh classes B and C); cinacalcet exposure and half-life are increased; monitor serum calcium, serum phosphorus and iPTH closely.
• Renal impairment: In the U.S., the long-term safety and efficacy of cinacalcet has not been evaluated in chronic kidney disease (CKD) patients with hyperparathyroidism not requiring dialysis. Not indicated for CKD patients not receiving dialysis. Although possibly related to lower baseline calcium levels, clinical studies have shown an increased incidence of hypocalcemia (<8.4 mg/dL) in patients not requiring dialysis.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; seizure threshold is lowered by significant serum calcium reductions. Monitor calcium levels closely.
Concurrent drug therapy issues:
• CYP2D6: Cinacalcet is a strong inhibitor of CYP2D6. If on concurrent therapy with a CYP2D6 substrate, dosage adjustment of the CYP2D6 substrate may be necessary.
• CYP3A4: Monitor serum calcium and iPTH concentrations closely in patients on concurrent CYP3A4 inhibitors; dosage adjustment may be required.
Adverse Reactions
>10%:
Central nervous system: Fatigue (12% to 21%), headache (≤21%), depression (10% to 18%)
Endocrine & metabolic: Hypocalcemia (≤66%), dehydration (≤24%), hypercalcemia (12% to 21%)
Gastrointestinal: Nausea (31% to 66%), vomiting (27% to 52%), diarrhea (≤21%), anorexia (6% to 21%), constipation (10% to 18%)
Hematologic: Anemia (6% to 17%)
Neuromuscular & skeletal: Parasthesia (14% to 29%), fracture (12% to 21%), weakness (7% to 17%), arthralgia (6% to 17%), myalgia (≤15%), limb pain (10% to 12%)
Respiratory: Upper respiratory infection (10% to 12%)
1% to 10%:
Cardiovascular: Hypertension (≤7%)
Central nervous system: Dizziness (≤10%), seizure (1%)
Endocrine & metabolic: Testosterone decreased
Neuromuscular & skeletal: Chest pain (noncardiac; ≤6%)
Postmarketing and/or case reports: Adynamic bone disease, angioedema, arrhythmia, heart failure, hypersensitivity reactions, hypotension (idiosyncratic), rash, urticaria
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (strong)
Drug Interactions
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Cinacalcet. Exceptions: Itraconazole. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions are required with concomitant use of a strong CYP2D6 inhibitor except in the treatment of major depressive disorder. Consult labeling for specific recommendations. Risk D: Consider therapy modification
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Propafenone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Tacrolimus: Cinacalcet may decrease the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Cinacalcet may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Tricyclic Antidepressants: Cinacalcet may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food increases bioavailability. Management: Administer with food or shortly after a meal.
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Increases the sensitivity of the calcium-sensing receptor on the parathyroid gland thereby, concomitantly lowering parathyroid hormone (PTH), serum calcium, and serum phosphorus levels, preventing progressive bone disease and adverse events associated with mineral metabolism disorders.
Pharmacodynamics/Kinetics
Distribution: Vd: ~1000 L
Protein binding: ~93% to 97%
Metabolism: Hepatic (extensive) via CYP3A4, 2D6, 1A2; forms inactive metabolites
Half-life elimination: Terminal: 30-40 hours; moderate hepatic impairment: 65 hours; severe hepatic impairment: 84 hours
Time to peak, plasma: ~2-6 hours
Excretion: Urine ~80% (as metabolites); feces ~15%
Dosage
Oral: Adults: Do not titrate dose more frequently than every 2-4 weeks. Dosage adjustment may be required in patients on concurrent CYP3A4 inhibitors.
Secondary hyperparathyroidism: Initial: 30 mg once daily (maximum daily dose: 180 mg); increase dose incrementally (60 mg, 90 mg, 120 mg, 180 mg once daily) as necessary to maintain iPTH level between 150-300 pg/mL.
Parathyroid carcinoma, primary hyperparathyroidism: Initial: 30 mg twice daily (maximum daily dose: 360 mg daily as 90 mg 4 times/day); increase dose incrementally (60 mg twice daily, 90 mg twice daily, 90 mg 3-4 times/day) as necessary to normalize serum calcium levels.
Elderly: No adjustment required; refer to adult dosing
Dosage adjustment for hypocalcemia:
If serum calcium >7.5 mg/dL but <8.4 mg/dL or if hypocalcemia symptoms occur: Use calcium-containing phosphate binders and/or vitamin D to raise calcium levels.
If serum calcium <7.5 mg/dL or if hypocalcemia symptoms persist and the dose of vitamin D cannot be increased: Withhold cinacalcet until serum calcium ≥8 mg/dL and/or symptoms of hypocalcemia resolve. Reinitiate cinacalcet at the next lowest dose.
If iPTH <150-300 pg/mL: Reduce dose or discontinue cinacalcet and/or vitamin D.
Dosage adjustment in renal impairment: No adjustment required.
Dosage adjustment in hepatic impairment: Patients with moderate-to-severe dysfunction (Child-Pugh classes B and C) have an increased exposure to cinacalcet and increased half-life. Dosage adjustments may be necessary based on serum calcium, serum phosphorus and/or iPTH.
Administration: Oral
Administer with food or shortly after a meal. Do not break or divide tablet; should be taken whole.
Monitoring Parameters
Secondary hyperparathyroidism: Serum calcium and phosphorus levels prior to initiation and within a week of initiation or dosage adjustment; iPTH should be measured 1-4 weeks after initiation or dosage adjustment. After the maintenance dose is established, monthly calcium and phosphorus levels and iPTH every 1-3 months are required. Wait at least 12 hours after dose before drawing iPTH levels.
Parathyroid carcinoma and primary hyperparathyroidism: Serum calcium levels prior to initiation and within a week of initiation or dosage adjustment; once maintenance dose is established, obtain serum calcium every 2 months.
Reference Range
CKD K/DOQI guidelines definition of stages; chronic disease is kidney damage or GFR <60 mL/minute/1.73 m2 for ≥3 months:
Stage 2: GFR 60-89 mL/minute/1.73 m2 (kidney damage with mild decrease GFR)
Stage 3: GFR 30-59 mL/minute/1.73 m2 (moderate decrease GFR)
Stage 4: GFR 15-29 mL/minute/1.73 m2 (severe decrease GFR)
Stage 5: GFR <15 mL/minute/1.73 m2 or dialysis (kidney failure)
Target range for iPTH: Adults:
Stage 3 CKD: 35-70 pg/mL
Stage 4 CKD: 70-110 pg/mL
Stage 5 CKD: 150-300 pg/mL
Serum phosphorus: Adults:
Stage 3 and 4 CKD: ≥2.7 to <4.6 mg/dL
Stage 5 CKD: 3.5-5.5 mg/dL
Serum calcium-phosphorus product: Adults: Stage 3-5 CKD: <55 mg2/dL2
Dietary Considerations
Take with food or shortly after a meal. May be taken with vitamin D and/or phosphate binders.
Patient Education
Take with food; do not break, chew, or crush tablet (swallow whole). You may experience dizziness, nausea, vomiting, loss of appetite, or diarrhea. Report any muscle cramping, twitches, tremors, or spasms; chest pain or palpitations; or unresolved gastrointestinal disturbance.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common
Mental Health: Effects on Psychiatric Treatment
Gastrointestinal side effects are common; these effects may be additive with concurrent use of SSRIs, lithium, or valproate. Cinacalcet may increase levels of amitriptyline and nortriptyline; monitor for increased effects and/or serum levels.
Nursing: Physical Assessment/Monitoring
Use caution with history of seizure disorder; assess serum calcium levels closely prior to initiating therapy, after dose change, and regularly during maintenance therapy. Monitor for hypocalcemia (paresthesias, myalgia, cramping, tetany, seizures) at beginning of therapy and regularly thereafter.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral:
Sensipar®: 30 mg, 60 mg, 90 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Sensipar)
30 mg (30): $449.00
60 mg (30): $935.03
90 mg (30): $1304.06
References
Block GA, Martin KJ, de Francisco AL, et al, “Cinacalcet for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis,” N Engl J Med, 2004, 350(15):1516-25.
Eknoyan G, Levin A, and Levin NW, “Bone Metabolism and Disease in Chronic Kidney Disease,” Am J Kidney Dis, 2003, 42(4 Suppl 3):1-201.
Marcocci C, Chanson P, Shoback D, et al, “Cinacalcet Reduces Serum Calcium Concentrations in Patients With Intractable Primary Hyperparathyroidism,” J Clin Endocrinol Metab, 2009, 94(8):2766-72.
Moe SM, Cunningham J, Bommer J, et al, “Long-Term Treatment of Secondary Hyperparathyroidism With the Calcimimetic Cinacalcet HCl,” Nephrol Dial Transplant, 2005, 20(10):2186-93.
National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Guideline 13: Treatment of Bone Disease in Chronic Kidney Disease. Available at http://www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm
Silverberg SJ, Rubin MR, Faiman C, et al, “Cinacalcet Hydrochloride Reduces the Serum Calcium Concentration in Inoperable Parathyroid Carcinoma,” J Clin Endocrinol Metab, 2007, 92(10):3803-8.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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