Sensipar

Calcimimetics

Administer with food or shortly after a meal.

Administer whole. Do not chew, crush, or divide tablets.

bone fractures / Delayed / 17.0-17.0
heart failure / Delayed / 2.0-2.0
seizures / Delayed / 1.4-1.4
arrhythmia exacerbation / Early / Incidence not known
angioedema / Rapid / Incidence not known
GI bleeding / Delayed / Incidence not known

hypocalcemia / Delayed / 66.0-80.0
hypercalcemia / Delayed / 17.0-17.0
dehydration / Delayed / 15.0-15.0
constipation / Delayed / 13.0-13.0
depression / Delayed / 13.0-13.0
anemia / Delayed / 13.0-13.0
hypotension / Rapid / 7.0-7.0
hypertension / Early / 7.0-7.0
chest pain (unspecified) / Early / 6.0-6.0
osteodystrophy / Delayed / Incidence not known
QT prolongation / Rapid / Incidence not known

nausea / Early / 31.0-63.0
vomiting / Early / 27.0-46.0
diarrhea / Early / 21.0-21.0
paresthesias / Delayed / 20.0-20.0
fatigue / Early / 17.0-17.0
anorexia / Delayed / 6.0-15.0
myalgia / Early / 15.0-15.0
asthenia / Delayed / 7.0-15.0
headache / Early / 13.0-13.0
arthralgia / Delayed / 13.0-13.0
infection / Delayed / 5.0-11.0
dizziness / Early / 10.0-10.0
rash / Early / 2.2-2.2
urticaria / Rapid / Incidence not known

Sensipar

Rx

Oral calcimimetic agent that directly reduces parathyroid hormone
Used for chronic kidney disease with secondary hyperparathyroidism (dialysis patients) and hypercalcemia due to parathyroid carcinoma or primary hyperparathyroidism in patients unable to undergo parathyroidectomy
Contraindicated in patients with hypocalcemia

Initially, 30 mg PO twice daily. Dosage should be titrated every 2 to 4 weeks through sequential doses of 60 mg PO twice daily, 90 mg PO twice daily, and 90 mg PO 3 to 4 times daily as necessary to normalize serum calcium concentrations. Measure serum calcium within 1 week of initiation or dose adjustment. Once maintenance dose has been established, measure serum calcium every 2 months.

Initially, 30 mg PO once daily. Serum calcium and phosphorus should be measured within 1 week. Intact parathyroid hormone (iPTH) serum concentration should be measured 1 to 4 weeks after initiation or dose adjustment. Titrate every 2 to 4 weeks through sequential doses of 60, 90, 120, and 180 mg PO once daily to a target iPTH concentration consistent with the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) recommendation for CKD patients undergoing dialysis (150 to 300 pg/mL). During dose titration, serum calcium concentrations should be monitored frequently; low concentrations of calcium should be treated with supplemental calcium, a calcium-based phosphate binder, or initiating/increasing the dose of vitamin D. Doses of cinacalcet titrated up to 300 mg PO once daily have been safely administered to patients receiving dialysis.

Preliminary data from a study in 54 patients with stage 3 or 4 CKD indicate that cinacalcet is effective in decreasing iPTH concentrations. In this study, patients were initiated on 30 mg PO once daily and titrated every 3 weeks to a maximum dose of 180 mg PO once daily for iPTH concentrations that did not decrease by at least 30% as compared to baseline. After 18 weeks of treatment, 56% of patients receiving cinacalcet compared to 19% of patients receiving placebo experienced a decrease in iPTH concentrations of 30% or more (p = 0.006); furthermore, iPTH concentrations decreased by a mean of 32% compared to baseline in patients taking cinacalcet compared to an increase of 6% in patients taking placebo (p less than 0.001). At study end, 52% of patients were receiving 30 mg PO once daily, and 30% were receiving 60 mg PO once daily. Serum calcium concentrations decreased by an average of 7% and the mean calcium concentration remained within the normal range throughout the study. Approximately 28% of patients were receiving vitamin D analogs at study start, and approximately 43% were receiving phosphate binders. Of note, the manufacturer reports of another study in which the majority of patients (80%) not requiring dialysis experienced at least one serum concentration of calcium less than 8.4 mg/dL.

Initially, 30 mg PO twice daily. Dosage should be titrated every 2 to 4 weeks through sequential doses of 60 mg PO twice daily, 90 mg PO twice daily, and 90 mg PO 3 to 4 times daily as necessary to normalize serum calcium concentrations. Measure serum calcium within 1 week of initiation or dose adjustment. Once maintenance dose has been established, measure serum calcium every 2 months.

Initially, 30 mg PO once daily after discontinuing etelcalcetide for at least 4 weeks prior to initiating cinacalcet. Ensure corrected serum calcium is at or above the lower limit of normal prior to cinacalcet initiation.[28126]

In patients with moderate and severe hepatic impairment, parathyroid hormone and serum calcium concentrations should be closely monitored throughout treatment with cinacalcet. Dosage reduction may be necessary, however, no quantitative guidelines are available. The AUC values for cinacalcet in patients with moderate to severe hepatic disease are 2.4 and 4.2 times greater, respectively, than the values observed for normal patients.

No adjustments are necessary.
 
Intermittent hemodialysis
No adjustments are necessary. Cinacalcet is highly protein bound and is not significantly removed by dialysis.

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with cinacalcet is necessary; consider increasing the dose of dihydrocodeine as needed. If cinacalcet is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A. Cinacalcet is a moderate inhibitor of CYP2D6. Concomitant use of dihydrocodeine with cinacalcet can increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Adagrasib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of adagrasib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Amoxapine: (Major) Lower doses of amoxapine may be required during concurrent use of cinacalcet due to the potential for increased amoxapine exposure. If cinacalcet is discontinued, an increased dose of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate; cinacalcet is a CYP2D6 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of clarithromycin and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of cinacalcet. Patients receiving both a CYP3A inhibitor plus cinacalcet may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; cinacalcet is a moderate CYP2D6 inhibitor.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Atazanavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of atazanavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Atazanavir; Cobicistat: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of atazanavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%. (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Brexpiprazole: (Moderate) Use caution if coadministration of cinacalcet with brexpiprazole is necessary, as the systemic exposure of brexpiprazole may be increased resulting in an increase in brexpiprazole-related adverse reactions. Reduce the dose of brexpiprazole to one-quarter (25%) of the usual dose if brexpiprazole and cinacalcet are coadministered with a moderate to strong inhibitor of CYP3A. If cinacalcet is discontinued, adjust the brexpiprazole dosage to its original level. Brexpiprazole is a CYP3A and CYP2D6 substrate; cinacalcet is a moderate CYP2D6 inhibitor. Concomitant use of moderate CYP2D6 inhibitors with a strong or moderate CYP3A inhibitor increased the exposure of brexpiprazole compared to use of brexpiprazole alone.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with cinacalcet is necessary. If cinacalcet is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ceritinib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ceritinib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Chloramphenicol: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of chloramphenicol and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with cinacalcet is necessary; consider increasing the dose of dihydrocodeine as needed. If cinacalcet is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A. Cinacalcet is a moderate inhibitor of CYP2D6. Concomitant use of dihydrocodeine with cinacalcet can increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Chlorpromazine: (Moderate) Monitor for an increase in chlorpromazine-related adverse reactions, including QT prolongation, anticholinergic effects, orthostasis, and somnolence, if coadministration with cinacalcet is necessary. Concomitant use may increase chlorpromazine exposure. Chlorpromazine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Clarithromycin: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of clarithromycin and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with cinacalcet and monitor for adverse reactions. If cinacalcet is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP2D6 and cinacalcet is a moderate CYP2D6 inhibitor.
Cobicistat: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Codeine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with cinacalcet may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of cinacalcet could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If cinacalcet is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Cinacalcet is a moderate inhibitor of CYP2D6.
Darunavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of darunavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Darunavir; Cobicistat: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%. (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of darunavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%. (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of darunavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Delavirdine: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of delavirdine and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Denosumab: (Moderate) Monitor serum calcium, phosphorus, and magnesium concentrations within 14 days of denosumab injection during concurrent treatment with calcimimetics such as cinacalcet. The risk for hypocalcemia and other disturbances of mineral metabolism may increase during coadministration. Monitor serum calcium concentrations closely in patients with severe renal impairment (CrCl less than 30 mL/minute) or renal failure (and/or on dialysis) receiving calcimimetics. An increased risk of hypocalcemia was seen in clinical trials involving patients with renal dysfunction. Instruct patients to seek medical care if symptoms of hypocalcemia develop.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with cinacalcet due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a major substrate of CYP2D6 and cinacalcet is a moderate CYP2D6 inhibitor. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with cinacalcet due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a major substrate of CYP2D6 and cinacalcet is a moderate CYP2D6 inhibitor. Concurrent use of CYP2D6 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dutasteride; Tamsulosin: (Moderate) Use caution if coadministration of cinacalcet with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Eliglustat: (Major) Reduce the dose of eliglustat to 84 mg once daily in patients who are extensive or intermediate CYP2D6 metabolizers (EMs or IMs) and receiving cinacalcet. Eliglustat is contraindicated in EMs and IMs who are receiving cinacalcet plus a strong or moderate CYP3A inhibitor. Eliglustat is contraindicated in poor metabolizers (PMs) who are receiving cinacalcet plus a strong CYP3A inhibitor and should be avoided, if possible, in patients who are receiving cinacalcet plus a moderate CYP3A inhibitor. Concomitant use may increase eliglustat exposure. Eliglustat is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. A moderate CYP2D6 inhibitor is predicted to increase eliglustat overall exposure by 4.5-fold and 1.6-fold in extensive and intermediate metabolizers, respectively. Moderate CYP2D6s inhibitors alone are not expected to affect eliglustat concentrations in CYP2D6 poor metabolizers (PMs).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of cobicistat and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Etelcalcetide: (Major) Avoid the concomitant use of etelcalcetide and cinacalcet. Discontinue cinacalcet at least 7 days prior to starting etelcalcetide, and initiate etelcalcetide treatment at 5 mg IV 3 times weekly. Ensure corrected serum calcium is at or above lower limit of normal prior to etelcalcetide initiation. Concurrent use of etelcalcetide with another oral calcium-sensing receptor agonist may result in severe, life-threatening, hypocalcemia.
Flecainide: (Moderate) Monitor for an increase in flecainide-related adverse reactions, including QT prolongation, if coadministration with cinacalcet is necessary. Flecainide is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. Plasma concentrations of flecainide may increase, especially in extensive CYP2D6 metabolizers.
Fluoxetine: (Moderate) Monitor for increased fluoxetine-related adverse effects if coadministered with cinacalcet. Concomitant use may increase fluoxetine exposure. Fluoxetine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with cinacalcet is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and cinacalcet is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during cinacalcet treatment due to the risk of increased cinacalcet exposure and adverse reactions. Cinacalcet is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with cinacalcet may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of cinacalcet could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If cinacalcet is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6; cinacalcet is a moderate inhibitor of CYP2D6.
Idelalisib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of idelalisib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Indinavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of indinavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Itraconazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of itraconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ketoconazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ketoconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of clarithromycin and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Letermovir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of letermovir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and letermovir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Levoketoconazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ketoconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Lofexidine: (Moderate) Monitor for orthostatic hypotension and bradycardia during concurrent use of lofexidine and cinacalcet. Coadministration may increase lofexidine exposure. Lofexidine is a CYP2D6 substrate; cinacalcet is a CYP2D6 inhibitor. Coadministration with a strong CYP2D6 inhibitor increased the lofexidine AUC by 28%.
Lonafarnib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of lonafarnib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Lopinavir; Ritonavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ritonavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Maprotiline: (Moderate) Monitor for an increase in maprotiline-related adverse reactions if coadministration with cinacalcet is necessary; a dose reduction of maprotiline may be necessary. Concurrent use may increase exposure of maprotiline. Maprotiline is a CYP2D6 substrate and cinacalcet is a CYP2D6 inhibitor.
Meclizine: (Moderate) Monitor for meclizine-related adverse effects, such as drowsiness and anticholinergic effects, when coadministered with cinacalcet. Concomitant use may increase the exposure to meclizine. Meclizine is a CYP2D6 substrate and cinacalcet is a CYP2D6 inhibitor.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of cinacalcet is necessary. If cinacalcet is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; cinacalcet is a moderate CYP2D6 inhibitor. Concomitant use with cinacalcet can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Metoprolol: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with cinacalcet. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and cinacalcet is a CYP2D6 inhibitor.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for metoprolol-related adverse reactions, including bradycardia and hypotension, during coadministration with cinacalcet. Concomitant use may increase metoprolol serum concentrations which would decrease the cardioselectivity of metoprolol. Metoprolol is a CYP2D6 substrate and cinacalcet is a CYP2D6 inhibitor.
Mexiletine: (Moderate) Monitor for increased toxicity of mexiletine if coadministered with cinacalcet. Coadministration may increase serum concentrations of mexiletine. Mexiletine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Mifepristone: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of mifepristone and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with cinacalcet; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with cinacalcet; adjust the nebivolol dose according to blood pressure response. Concomitant use may increase the exposure of nebivolol. Nebivolol is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Nefazodone: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of nefazodone and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Nelfinavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of nelfinavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ritonavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Olanzapine; Fluoxetine: (Moderate) Monitor for increased fluoxetine-related adverse effects if coadministered with cinacalcet. Concomitant use may increase fluoxetine exposure. Fluoxetine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and cinacalcet is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and cinacalcet may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If cinacalcet is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with cinacalcet is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and cinacalcet is a strong CYP2D6 inhibitor.
Pimozide: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with cinacalcet. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; cinacalcet is a moderate CYP2D6 inhibitor.
Posaconazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of posaconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with cinacalcet; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and cinacalcet with a CYP3A inhibitor. Propafenone is a CYP3A and CYP2D6 substrate; cinacalcet is a moderate CYP2D6 inhibitor.
Propranolol: (Moderate) Monitor for increased propranolol adverse reactions, including bradycardia and hypotension, during coadministration of cinacalcet as concurrent use may increase propranolol exposure. Propranolol is a CYP2D6 substrate and cinacalcet is moderate CYP2D6 inhibitor.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased propranolol adverse reactions, including bradycardia and hypotension, during coadministration of cinacalcet as concurrent use may increase propranolol exposure. Propranolol is a CYP2D6 substrate and cinacalcet is moderate CYP2D6 inhibitor.
Ribociclib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ribociclib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ribociclib; Letrozole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ribociclib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ritonavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ritonavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Saquinavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of saquinavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Tamsulosin: (Moderate) Use caution if coadministration of cinacalcet with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increased treatment-related adverse reactions including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Thioridazine: (Contraindicated) Coadministration of thioridazine and cinacalcet is contraindicated due to the potential for increased thioridazine exposure. Increased plasma concentrations of thioridazine are expected to increase the prolongation of the QTc interval associated with thioridazine and may increase the risk of serious, potentially fatal, cardiac arrhythmias, such as torsade de pointes type arrhythmias. Thioridazine is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor.
Tipranavir: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of tipranavir and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with cinacalcet is necessary. If cinacalcet is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol, signs of opioid withdrawal, seizures, or serotonin syndrome if coadministration with cinacalcet is necessary. If cinacalcet is discontinued, consider a dose reduction of tramadol and frequently monitor for signs of respiratory depression and sedation. Tramadol is a CYP2D6 substrate and cinacalcet is a moderate CYP2D6 inhibitor. Concomitant use of tramadol with CYP2D6 inhibitors can increase the plasma concentration of tramadol and decrease the plasma concentration of the active metabolite M1. Since M1 is a more potent mu-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who have developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Tricyclic antidepressants: (Moderate) Monitor for an increase in tricyclic antidepressant (TCA)-related adverse reactions if coadministration with cinacalcet is necessary; a dose reduction of TCA may be necessary. Concurrent use may increase the exposure of TCAs which are CYP2D6 substrates; cinacalcet is a CYP2D6 inhibitor.
Tucatinib: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of tucatinib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of clarithromycin and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Voriconazole: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of voriconazole and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.

Cinacalcet/Cinacalcet Hydrochloride/Sensipar Oral Tab: 30mg, 60mg, 90mg

300 mg/day PO for dialysis patients with secondary hyperparathyroidism; 360 mg/day PO for hypercalcemia associated with parathyroid carcinoma or primary hyperparathyroidism.

300 mg/day PO for dialysis patients with secondary hyperparathyroidism; 360 mg/day PO for hypercalcemia associated with parathyroid carcinoma or primary hyperparathyroidism.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

The course of chronic kidney disease leads to the development of altered calcium (hypocalcemia) and phosphorus (hyperphosphatemia) metabolism, increased parathyroid hormone (PTH) levels and eventually to subsequent bone disease and vascular and soft tissue calcifications. Hyperphosphatemia results from decreased renal elimination of phosphorus. Increased phosphorus levels directly suppress calcitriol production. Calcium levels decrease as a result of suppressed calcitriol production from the hyperphosphatemia and reduced calcium absorption from the GI tract. Through a feedback mechanism, hypocalcemia, hyperphosphatemia and decreased calcitriol production stimulate the release of parathyroid hormone and proliferation of parathyroid cells leading to secondary hyperparathyroidism. Bone resorption and formation are influenced by many hormonal and non-hormonal factors; hormonal factors affecting bone structure include altered PTH concentrations. When parathyroid hormone levels are too high, osteoclasts are stimulated and result in high bone turnover, leading to decreased cortical bone and bone strength and increased risk of fracture.
 
The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH secretion. Cinacalcet, mimicking calcium, increases the sensitivity of this calcium-sensing receptor, and PTH secretion is reduced. The reduction in PTH is associated with a concomitant decrease in serum calcium levels. The feedback loop is hindered and eventually slows the progression of bone disease and the systemic consequences of deranged mineral metabolism.

Cinacalcet is administered orally. It is approximately 93 to 97% bound to plasma protein(s). The volume of distribution is approximately 1,000 L, indicating extensive distribution. The plasma concentrations of major circulating metabolites, including hydrocinnamic and glucuronidated dihydrodiols, markedly exceed parent drug concentrations. The hydrocinnamic metabolite was shown to be inactive while the glucuronide conjugates have minimal or no calcimimetic activity. The primary route of elimination of the metabolites was renal excretion. Approximately 80% of the oral dose was recovered in the urine and 15% in the feces.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2D6, CYP3A4, CYP1A2
Cinacalcet is a strong inhibitor of CYP2D6. It is metabolized by multiple enzymes, primarily CYP3A4, CYP2D6, and CYP1A2.

After oral administration of cinacalcet, Cmax is achieved in approximately 2 to 6 hours. Administration with a high-fat meal increased Cmax and AUC by 82% and 68%, respectively, and increased 65% and 50% when given with a low-fat meal compared to a fasting state. The terminal half-life is 30 to 40 hours and steady-state drug concentrations are achieved within 7 days. The Cmax and AUC increase proportionally over the dose range of 30 to 180 mg PO once daily. However, the pharmacokinetic profile does not change over time with this dose range.

Data on the use of cinacalcet in human pregnancy are limited to case reports and insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies of rats exposed to cinacalcet at 2 to 3 times the systemic concentrations (based on AUC) at the maximum recommended human dose (MRHD) of 180 mg/day during organogenesis through weaning, peripartum and early postnatal pup loss and reduced pup body weight gain were observed in the presence of maternal hypocalcemia. When rats and rabbits were given oral doses resulting in exposures less than with a human oral dose of 180 mg/day based on AUC comparisons, no adverse fetal effects were observed. Reductions in maternal food consumption and body weight gain were noted. Cinacalcet has been shown to cross the placental barrier in rabbits.

There are no data on the presence of cinacalcet in human milk, the effects on the breast-fed infant, or the effects on milk production. Cinacalcet is excreted into the milk of rats. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cinacalcet and any potential adverse effects on the breast-fed infant from cinacalcet or the underlying maternal condition.