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Pronunciation
(sin a KAL cet)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
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
Note: In Canada, cinacalcet is approved only for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis
Use: Unlabeled/Investigational
Primary hyperparathyroidism
Pregnancy Risk Factor
C
Pregnancy Considerations
In animal studies, there were no teratogenic effects seen. There are no adequate or well-controlled studies in pregnant women.
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
Hypersensitivity to cinacalcet or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Adynamic bone disease: May develop if 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).
• Hypocalcemia: If hypocalcemia develops or symptoms of hypocalcemia (eg, cramps, myalgia, paresthesia, seizure, tetany) occur during treatment, consider initiating supplemental calcium, calcium-based phosphate binder, or vitamin D or temporarily withholding cinacalcet. Serum calcium levels should be ?8.4 mg/dL prior to initiating treatment. Dosage reductions may be necessary upon reinitiation of cinacalcet treatment.
• 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:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; idiosyncratic hypotension, worsening of heart failure, and/or arrhythmia have been reported in patients with impaired cardiovascular function.
• Hepatic impairment: Use with caution in patients with moderate-to-severe hepatic impairment (Child-Pugh classes B & C); cinacalcet exposure and half-life are increased; monitor 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.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children.
Adverse Reactions
>10%:
Endocrine & metabolic: Hypocalcemia
Gastrointestinal: Nausea (31%), vomiting (27%), diarrhea (21%)
Neuromuscular & skeletal: Myalgia (15%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (10%), seizure (1%)
Endocrine & metabolic: Testosterone decreased
Gastrointestinal: Anorexia (6%)
Neuromuscular & skeletal: Weakness (7%), chest pain (noncardiac; 6%)
Postmarketing and/or case reports: Adynamic bone disease, angioedema, arrhythmia (in patients with cardiac dysfunction), heart failure (worsening; in patients with cardiac dysfunction), hypersensitivity reactions, hypotension (idiosyncratic; in patients with cardiac dysfunction), rash, urticaria
Metabolism/Transport Effects
Substrate of CYP1A2, 2D6, 3A4; Inhibits CYP2D6 (major)
Drug Interactions
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Cinacalcet. Exceptions: Itraconazole. 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
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
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
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
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
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.
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 PTH and serum calcium levels.
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: prolonged 33%; severe hepatic impairment: prolonged 70%
Time to peak, plasma: Nadir in iPTH levels: ~2-6 hours postdose
Excretion: Urine ~80% (as metabolites); feces ~15%
Dosage
Oral: Adults: Do not titrate dose more frequently than every 2-4 weeks.
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: 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.
Administration: Oral
Administer with food or shortly after a meal. Do not break tablet; should be taken whole.
Monitoring Parameters
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 PTH levels.
Parathyroid carcinoma: Serum calcium levels prior to initiation and within a week of initiation or dosage adjustment; once maintenance dose is established, obtain serum calcium level 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
Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed with food; do not break, chew, or crush tablet (swallow whole). Do not take more than prescribed. You may experience dizziness (use caution when driving or engaged in potentially hazards tasks until response to drug is known); nausea, vomiting, or loss of appetite (good mouth care, small frequent meals, sucking lozenges, or chewing gum may help); diarrhea. Report any muscle cramping, twitches, tremors, or spasms; chest pain or palpitations; unresolved gastrointestinal disturbance, or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant or breast-feed.
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 or dose change and regularly during maintenance therapy. Assess other pharmacological or herbal products patient may be taking for potential interactions. Assess results of laboratory tests, therapeutic response (calcium levels), and adverse reactions (eg, hypocalcemia [paresthesias, myalgia, cramping, tetany, convulsions]) frequently at beginning of therapy and regularly thereafter. Teach patient possible side effects, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Sensipar®: 30 mg, 60 mg, 90 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Sensipar)
30 mg (30): $387.94
60 mg (30): $791.28
90 mg (30): $1089.02
References
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.
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: www.kidney.org/professionals/kdoqi/guidelines_bone/index.htm. Accessed March 18, 2004.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2010
Content last modified January 2010
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