Version May 2024
Hyperparathyroidism, primary: Oral: Initial: 30 mg twice daily; may increase dose incrementally (to 60 mg twice daily, 90 mg twice daily, and 90 mg 3 or 4 times daily) every 2 to 4 weeks as necessary to normalize serum calcium levels.
Hyperparathyroidism, secondary (dialysis-dependent chronic kidney disease):
Note: In patients with severely elevated parathyroid hormone (PTH) levels (eg, >800 pg/mL), cinacalcet monotherapy may be inadequate to achieve target PTH levels; combination therapy (eg, with calcitriol or vitamin D analogs and/or phosphate binders) may be required (Ref).
Oral: Initial: 30 mg once daily; may increase dose in 30 mg/day increments every 2 to 4 weeks up to 180 mg once daily as necessary to maintain target PTH levels.
Conversion from etelcalcetide : Discontinue etelcalcetide for at least 4 weeks prior to initiating cinacalcet.
Parathyroid carcinoma, hypercalcemia treatment: Oral: Initial: 30 mg twice daily; may increase dose incrementally (to 60 mg twice daily, 90 mg twice daily, and 90 mg 3 to 4 times daily) every 2 to 4 weeks as necessary to normalize serum calcium levels.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed: No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Not significantly dialyzed: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate to severe impairment (Child-Pugh class B or C): There are no specific dosage adjustments provided in the manufacturer's labeling; exposure and half-life of cinacalcet is increased. Dosage adjustments may be necessary based on serum calcium, phosphorus, and/or parathyroid hormone levels.
Dosage adjustment for low parathyroid hormone levels:
Parathyroid hormone <150 pg/mL: Reduce dose or discontinue cinacalcet and/or vitamin D analog.
Dosage adjustment for hypocalcemia (patients with secondary hyperparathyroidism) :
If serum calcium >7.5 mg/dL but <8.4 mg/dL (>1.87 mmol/L but <2.1 mmol/L) and continuation of cinacalcet is desired: Mild (eg, serum calcium 8 to <8.4 mg/dL [2 to <2.1 mmol/L]) or asymptomatic hypocalcemia due to cinacalcet may not require treatment (Ref). In patients with more significant or symptomatic hypocalcemia, may consider use of calcium-containing phosphate binders, use of vitamin D analogs, and/or adjustment of dialysate calcium content to raise calcium levels while avoiding hypercalcemia.
If serum calcium <7.5 mg/dL (<1.87 mmol/L) or if hypocalcemia symptoms persist despite treatment: Withhold cinacalcet until serum calcium ≥8 mg/dL (≥2 mmol/L) and/or symptoms of hypocalcemia resolve. Reinitiate cinacalcet at the next lowest dose.
Refer to adult dosing.
(For additional information see "Cinacalcet: Pediatric drug information")
Hyperparathyroidism, secondary: Note: Should only be used when standard therapies have proven ineffective. Ensure calcium is in normal range before initiating therapy and monitor closely throughout treatment. Dosing based on patient's dry weight.
Children ≥3 years and Adolescents: Limited data available, optimal dosage not established in pediatric patients: Oral:
Weight-directed dosing: Initial: ≤0.2 mg/kg/dose once daily; may titrate every 4 weeks to reach target range of intact parathyroid hormone (iPTH) of 100 to 300 pg/mL. Maximum daily dose: 180 mg/day or 2.5 mg/kg/dose (whichever is lower) (Ref). Dosing based on a randomized, double-blind study (n=43) with an open-label phase (n=12) with secondary hyperparathyroidism on hemodialysis or peritoneal dialysis. Cinacalcet was started at ≤0.2 mg/kg/day in 22 patients (mean age: 13.3 ± 3.6 years) and titrated every 4 weeks to goal iPTH. For the efficacy endpoint phase, the mean weight adjusted dose was 1.54 mg/kg/day which corresponded to 50.4 mg/day. iPTH was decreased by ≥30% in 54% of patients receiving cinacalcet compared to 19% with placebo. Serum calcium was significantly reduced in patients receiving cinacalcet compared to placebo and severe hypocalcemia (<7.5 mg/dL) occurred in 3 patients, including 1 death where treatment-related cause could not be ruled out (corrected calcium was 5.3 mg/dL). This study was placed on hold following the reported death and ultimately terminated after 14 months. Despite the limited number of patients enrolled due to study termination, efficacy was still demonstrated (Ref). Note: Cinacalcet use in children <3 years and infants as young as 8 months has been described; however, variable dosing strategies were used or only single doses were administered (Ref).
Weight-band (fixed) dosing (Ref):
|
Weight Band |
Initial Dose |
Suggested Adjustment Doses |
|---|---|---|
|
≥10 to <12.5 kg |
1 mg once daily |
1 mg, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg |
|
≥12.5 to <25 kg |
2.5 mg once daily |
2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 30 mg |
|
≥25 to <36 kg |
5 mg once daily |
5 mg, 10 mg, 15 mg, 30 mg, 60 mg |
|
≥36 to <50 kg |
5 mg once daily |
5 mg, 10 mg, 15 mg, 30 mg, 60 mg, 90 mg |
|
≥50 to <75 kg |
10 mg once daily |
10 mg, 15 mg, 30 mg, 60 mg, 90 mg, 120 mg |
|
≥75 kg |
15 mg once daily |
15 mg, 30 mg, 60 mg, 90 mg, 120 mg, 180 mg |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Dosage adjustment for hypocalcemia (Ref): Children ≥3 years and Adolescents:
Corrected serum calcium at or below age-specific lower limit or symptoms of hypocalcemia (regardless of calcium concentration): Temporarily discontinue cinacalcet and administer calcium supplements, calcium-containing phosphate binders, and/or vitamin D to raise calcium.
Corrected serum calcium above age-specific lower limit and resolution of hypocalcemia symptoms: Re-initiate cinacalcet at a lower dose. If treatment is stopped for ≥14 days, restart at initial dose.
Dose adjustment based on iPTH (Ref): Children ≥3 years and Adolescents:
If iPTH is ≥100 to <150 pg/mL: Reduce dose.
If iPTH <100 pg/mL: Discontinue cinacalcet until iPTH is >150 pg/mL; restart at lower dose; if treatment has been stopped for >14 days, restart at initial dose.
There are no pediatric-specific dosage adjustments in the manufacturer's labeling; however, adjustment is unnecessary as cinacalcet is indicated for use in chronic kidney disease.
There are no pediatric-specific dosage adjustments in the manufacturer's labeling; in moderate to severe impairment, dosage adjustments may be necessary based on serum calcium, serum phosphorus, and/or intact parathyroid hormone.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypotension (12%)
Endocrine & metabolic: Hypocalcemia (<8.4 mg/dL: 6% to 75%; <7.5 mg/dL: 29% to 33%), hypoparathyroidism (intact parathyroid hormone <100 pg/mL: ≤11%)
Gastrointestinal: Nausea (29% to 31%), vomiting (26% to 27%), diarrhea (21%), abdominal pain (11%)
Nervous system: Headache (12%)
Neuromuscular & skeletal: Muscle spasm (11% to 18%), myalgia (15%), back pain (12%)
Respiratory: Dyspnea (13%), cough (12%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Endocrine & metabolic: Hyperkalemia (8%)
Gastrointestinal: Upper abdominal pain (8%), dyspepsia (7%), anorexia (6%), decreased appetite (6%), constipation (5%)
Hypersensitivity: Hypersensitivity reaction (9%)
Nervous system: Dizziness (7% to 10%), noncardiac chest pain (6%), seizure (≤3%)
Neuromuscular & skeletal: Asthenia (5% to 7%)
Respiratory: Upper respiratory tract infection (8%)
Frequency not defined: Hematologic & oncologic: Upper gastrointestinal hemorrhage
<1%, postmarketing, and/or case reports: Adynamic bone disease, angioedema, calcium pyrophosphate deposition disease, cardiac arrhythmia, cardiac failure, gastrointestinal hemorrhage, prolonged QT interval on ECG (secondary to hypocalcemia), skin rash, urticaria, ventricular arrhythmia (secondary to hypocalcemia)
Serum calcium less than the lower limit of normal range
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to any component of the formulation
Concerns related to adverse effects:
• Adynamic bone disease: May develop if parathyroid hormone levels are suppressed <100 pg/mL.
• Cardiovascular effects: QT prolongation and ventricular arrhythmia secondary to hypocalcemia may occur. 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. 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.
• GI effects: GI bleeding, mostly upper GI bleeding, have been reported (exact cause unknown); patients with risk factors for upper GI bleeding (eg, gastritis, esophagitis, ulcers, severe vomiting) may be at increased risk.
• Hypocalcemia: Life-threatening and fatal events associated with hypocalcemia have occurred. Use with caution in patients receiving concomitant therapies known to lower serum calcium concentrations. May require treatment interruption, dose reduction, or initiation (or dose increases) of calcium-based phosphate binder and/or vitamin D to raise serum calcium depending on calcium levels or symptoms of hypocalcemia. Do not initiate therapy if the corrected serum calcium is less than the lower limit of normal; corrected serum calcium must be at or above the lower limit of normal prior to initiation, dose increase, or reinitiation.
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.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; seizure threshold is lowered by significant serum calcium reductions.
Other warnings/precautions:
• Appropriate use: Not indicated for chronic kidney disease (CKD) patients not receiving dialysis. In the United States, the long-term safety and efficacy of cinacalcet has not been evaluated in CKD patients with hyperparathyroidism not requiring 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.
Severe hypocalcemia has been reported in pediatric patients receiving cinacalcet; monitor serum calcium closely. During a phase 3 clinical trial in pediatric dialysis patients (n=22; mean age: 13.3 years; age range: 6 to <18 years) with secondary hypoparathyroidism receiving cinacalcet, mild hypocalcemia (<8.4 mg/dL) was reported in 7 patients, moderate hypocalcemia (<8 mg/dL) was reported in 5 patients, and severe hypocalcemia (<7.5 mg/dL) was reported in 3 patients, including 1 fatality. The patient who died had a calcium of 5.3 mg/dL; the patient death was attributed to multifactorial reasons; however, association with cinacalcet treatment could not be ruled out (Warady 2019). Asymptomatic hypocalcemia has also been reported in pediatric patients. Half of the patients enrolled in an open-label, single-dose safety, tolerability, and pharmacokinetic study (n=12) developed asymptomatic hypocalcemia; calcium concentrations ranged from 2 to 2.2 mmol/L within 12 hours post dose (Padhi 2012). In a retrospective case series (n=6), asymptomatic hypocalcemia occurred in 2 patients including 1 patient who was refractory to treatment requiring discontinuation of cinacalcet for 5 months (Platt 2010).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sensipar: 30 mg, 60 mg, 90 mg
Generic: 30 mg, 60 mg, 90 mg
Yes
Tablets (Cinacalcet HCl Oral)
30 mg (per each): $2.83 - $34.60
60 mg (per each): $3.29 - $61.85
90 mg (per each): $3.31 - $92.77
Tablets (Sensipar Oral)
30 mg (per each): $32.27
60 mg (per each): $64.54
90 mg (per each): $96.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sensipar: 30 mg, 60 mg, 90 mg
Generic: 30 mg, 60 mg, 90 mg
Administer with food or shortly after a meal. Do not chew, crush, or divide tablet; administer whole.
Oral: Children ≥3 years and Adolescents: Administer with food or shortly after a meal. Administer tablets whole; do not chew, crush, or divide tablets. An extemporaneous preparation may be made if patients cannot swallow tablets.
Hyperparathyroidism, primary: Treatment of hypercalcemia in adults with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy.
Hyperparathyroidism, secondary: Treatment of secondary hyperparathyroidism in adults with chronic kidney disease on dialysis.
Parathyroid carcinoma, hypercalcemia treatment: Treatment of hypercalcemia in adults with parathyroid carcinoma.
Substrate of CYP1A2 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy
Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy
Amoxapine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy
Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Moderate) 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, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Risk C: Monitor therapy
Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Atomoxetine. Risk C: Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose when treating indications other than major depressive disorder. Risk C: Monitor therapy
Carvedilol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Cinacalcet. Risk C: Monitor therapy
Denosumab: May enhance the hypocalcemic effect of Calcimimetic Agents. Risk C: Monitor therapy
Desipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Desipramine. Risk C: Monitor therapy
Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Risk C: Monitor therapy
Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy
Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy
Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification
Etelcalcetide: Cinacalcet may enhance the hypocalcemic effect of Etelcalcetide. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flecainide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Flecainide. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Haloperidol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Iboga: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iboga. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy
Imipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Imipramine. Risk C: Monitor therapy
Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy
Lofepramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy
Mequitazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Mequitazine. Risk X: Avoid combination
Methadone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoclopramide. Risk C: Monitor therapy
Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy
Oliceridine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy
Olmutinib: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
PARoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Perhexiline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy
Perphenazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy
Pimozide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk C: Monitor therapy
Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Risk C: Monitor therapy
Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Propranolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Protriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy
RisperiDONE: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Sertindole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk C: Monitor therapy
Siponimod: Calcimimetic Agents may increase the serum concentration of Siponimod. Management: Coadministration of siponimod with drugs which are both moderate inhibitors of CYP2C9 and moderate or strong inhibitors of CYP3A4 is not recommended. Risk D: Consider therapy modification
Tacrolimus (Systemic): Cinacalcet may decrease the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification
Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Thioridazine. Risk X: Avoid combination
Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy
TraMADol: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy
Trimipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy
Valbenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. Risk C: Monitor therapy
Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Vortioxetine. Risk C: Monitor therapy
Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Food increases bioavailability. Management: Administer with food or shortly after a meal.
Information related to the use of cinacalcet in pregnant females is limited (Edling 2014; Horjus 2009; Nadarasa 2014; Rey 2016; Vera 2016).
It is not known if cinacalcet is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Monitor for signs/symptoms of hypocalcemia (eg, muscle spasms, myalgia, paresthesia, seizure, tetany). In patients on concurrent strong CYP3A4 inhibitors or with seizure disorders, closely monitor serum calcium and PTH levels. In patients with moderate to severe hepatic impairment, closely monitor serum calcium, PTH, and serum phosphorous levels. In patients at risk for GI bleeding (eg, gastritis, esophagitis, ulcers, severe vomiting), monitor for worsening of nausea and vomiting and for signs/symptoms of GI bleeding and ulceration. In patients at risk for QT prolongation, closely monitor albumin-corrected serum calcium levels and QT interval.
Secondary hyperparathyroidism: Serum calcium and phosphorus levels prior to initiation and within a week of initiation and frequently during dose titration; parathyroid hormone (PTH) 1 to 4 weeks after initiation or dosage adjustment (wait at least 12 hours after dose before drawing PTH levels). Once maintenance dose is established, obtain serum calcium levels monthly.
Primary hyperparathyroidism and parathyroid carcinoma: Serum calcium levels prior to initiation and within 1 week of initiation or dosage adjustment; once maintenance dose is established, obtain serum calcium every 2 months.
Note: Due to the complexity and interdependency of the laboratory parameters used for therapeutic decisions in patients with chronic kidney disease-mineral and bone disorder, serial assessments of serum phosphate, calcium, and parathyroid hormone (PTH) levels should be considered together (KDIGO 2017).
Calcium (total): Normal range: Adults: 8.5 to 10.5 mg/dL (2.12 to 2.62 mmol/L) (IOM 2011). Avoid hypercalcemia for chronic kidney disease (CKD) stages G3a to G5D (KDIGO 2017).
Phosphorus: 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L). Lower elevated phosphorus levels toward the normal range for CKD stages G3a to G5D (KDIGO 2017).
PTH:
CKD stage G3a to G5: Optimal PTH level is unknown; evaluate patients with progressively elevated PTH levels or if levels are consistently above the normal range (assay-dependent) (KDIGO 2017).
Dialysis patients: Maintain PTH levels within 2 to 9 times the ULN for the assay used (KDIGO 2017).
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.
Distribution: Vd: ~1,000 L
Protein binding: ~93% to 97%
Metabolism: Hepatic (extensive) via CYP3A4, 2D6, 1A2; forms inactive metabolites
Half-life elimination: Terminal: 30 to 40 hours; moderate hepatic impairment: 65 hours; severe hepatic impairment: 84 hours
Time to peak, plasma: ~2 to 6 hours; increased with food.
Excretion: Urine ~80% (as metabolites); feces ~15%
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 to 65 hours and 84 hours in patients with moderate and severe hepatic impairment, respectively.
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