Paricalcitol is administered orally once daily or 3 times weekly; the drug may be given without regard to meals.117 When paricalcitol is administered 3 times weekly, the drug should be administered no more frequently than every other day.117
Paricalcitol also is administered by direct IV injection at any time during dialysis; the drug should be administered IV no more frequently than every other day.110
Paricalcitol dosage must be individualized carefully according to serum or plasma intact parathyroid hormone (iPTH) concentrations and serum calcium and phosphorus concentrations.110,111,113,117 In patients receiving oral paricalcitol, serum calcium, serum phosphorus, and serum or plasma iPTH concentrations should be monitored at least every 2 weeks for 3 months after initiation of therapy or after subsequent dosage changes, then monthly for 3 months (once the dosage is stabilized), and every 3 months thereafter.117 The manufacturer recommends that iPTH concentrations be determined every 3 months in patients receiving parenteral paricalcitol; more frequent monitoring may be necessary during dosage adjustments.110 In addition, the manufacturer recommends that serum calcium and phosphorus concentrations be monitored frequently (e.g., twice weekly) during the initial dosage adjustments and after subsequent dosage changes and at least monthly once the dosage is stabilized in patients receiving parenteral paricalcitol.110
If use of a potent inhibitor of the cytochrome P-450 (CYP) 3A isoenzyme (e.g., atazanavir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, the fixed combination of lopinavir and ritonavir [lopinavir/ritonavir], nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) is initiated or discontinued in a patient receiving paricalcitol, serum calcium and iPTH concentrations should be monitored closely;110,117 paricalcitol dosage adjustment may be necessary.117
Dosage adjustment is not required in patients with mild to moderate hepatic impairment.110,117
Nephrology experts state that the optimal iPTH concentration for patients with stage 3a (estimated glomerular filtration rate [eGFR] 45-59 mL/minute per 1.73 m2) to stage 5 (eGFR less than 15 mL/minute per 1.73 m2) chronic kidney disease (CKD) who are not undergoing dialysis is unknown, but modest increases in iPTH concentration may represent an appropriate adaptive response to declining renal function.128,129 For patients with stage 5 CKD undergoing dialysis, some experts suggest that iPTH concentrations may be maintained within a range of approximately 2-9 times the assay's upper limit of normal (ULN) (which may correspond to a range of approximately 130-600 pg/mL for commercially available assays130 ).128 Although some clinicians suggest that this range is too broad, available assays for PTH exhibit substantial variability; the previously recommended range of 150-300 pg/mL for patients with stage 5 CKD requiring dialysis was based on an assay that is no longer commercially available.126,130,131 Oversuppression of PTH may increase the risk of adynamic bone disease and should be avoided.126,131 (See Uses: Mineral and Bone Disorder Secondary to Chronic Renal Disease, in the Vitamin D Analogs General Statement 88:16.) Nephrology experts currently recommend that the individual values for serum calcium and phosphorus (evaluated together) be used instead of the mathematical construct of calcium times phosphorus product to guide clinical practice.126,128
Hyperparathyroidism Secondary to Chronic Renal Disease
The manufacturer states that the initial oral dosage of paricalcitol for the prevention and treatment of secondary hyperparathyroidism in adults with stage 3 or 4 CKD and a baseline serum iPTH concentration of 500 pg/mL or less is 1 mcg daily or 2 mcg 3 times weekly, while the initial dosage of paricalcitol for this indication in adults with stage 3 or 4 CKD and a baseline serum iPTH concentration exceeding 500 pg/mL is 2 mcg daily or 4 mcg 3 times weekly.117 Dosage of paricalcitol should be adjusted according to the patient's serum or plasma iPTH concentrations.117 If response is inadequate (i.e., iPTH concentration increases, remains unchanged, or is not reduced by at least 30%), the manufacturer states that dosage of paricalcitol may be increased by 1 mcg daily (e.g., from 1 mcg daily to 2 mcg daily) or 2 mcg 3 times weekly (e.g., from 2 mcg 3 times weekly to 4 mcg 3 times weekly) at 2- to 4-week intervals.117 The manufacturer states that dosage of paricalcitol should be maintained in patients whose iPTH concentrations have decreased by 30-60% from baseline values.117 Dosage of paricalcitol should be reduced as iPTH concentrations decline in response to therapy; if iPTH concentrations decrease by more than 60% or if iPTH concentrations decline to less than 60 pg/mL, the manufacturer states that the dosage of paricalcitol should be reduced by 1 mcg daily or 2 mcg 3 times weekly at 2- to 4-week intervals.117 Patients receiving the lowest dosage with the daily regimen (i.e., 1 mcg daily) who require a dosage reduction may receive 1 mcg 3 times weekly; if further dosage reduction is needed, paricalcitol therapy should be withheld as needed and reinitiated at a lower dosage by altering the dosing interval.117
The manufacturer states that the initial oral dose of paricalcitol (in mcg) for the prevention and treatment of secondary hyperparathyroidism in adults with stage 5 CKD undergoing hemodialysis or peritoneal dialysis may be calculated by dividing the baseline iPTH concentration (in pg/mL) by 80; the calculated dose should be administered 3 times weekly.117 To minimize the risk of hypercalcemia, therapy should be initiated only in those with an adjusted baseline serum calcium concentration of 9.5 mg/dL or less.117 Dosage of paricalcitol should be individualized according to the patient's serum or plasma iPTH concentrations, serum calcium concentrations, and serum phosphorus concentrations.117 The manufacturer states that the new dose of paricalcitol (in mcg) may be calculated by dividing the most recent iPTH concentration (in pg/mL) by 80.117 If serum calcium concentrations are elevated, the dose should be decreased by 2-4 mcg.117 As the iPTH concentration approaches the target range, small individualized dosage adjustments may be necessary to achieve a stable iPTH concentration.117 In situations where iPTH, calcium, or phosphorus is monitored less frequently than once weekly, the manufacturer states that a more modest initial and dose-titration ratio (e.g., iPTH concentration divided by 100) may be appropriate.117
The initial oral dosage of paricalcitol for the prevention and treatment of secondary hyperparathyroidism in pediatric patients 10-16 years of age with stage 3 or 4 CKD is 1 mcg 3 times weekly.117 Dosage of paricalcitol should be individualized according to the patient's serum or plasma iPTH concentrations, serum calcium concentrations, and serum phosphorus concentrations to maintain the iPTH concentration within the target range.117 Dosage may be increased in increments of 1 mcg 3 times weekly (i.e., from 1 mcg 3 times weekly to 2 mcg 3 times weekly) at intervals of 4 weeks.117 At any time during therapy, the administered dose may be decreased by 1 mcg.117 If dosage reduction is needed in a patient receiving the lowest dosage (1 mcg 3 times weekly), paricalcitol therapy should be withheld as needed and resumed when appropriate.117
The manufacturer states that the initial oral dose of paricalcitol (in mcg) for the prevention and treatment of secondary hyperparathyroidism in pediatric patients 10-16 years of age with stage 5 CKD undergoing hemodialysis or peritoneal dialysis may be calculated by dividing the baseline iPTH concentration (in pg/mL) by 120; the calculated dose should be rounded down to the nearest whole number and administered 3 times weekly.117 Dosage of paricalcitol should be individualized according to the patient's serum or plasma iPTH concentrations, serum calcium concentrations, and serum phosphorus concentrations to maintain the iPTH concentration within the target range.117 Dosage may be increased in increments of 1 mcg 3 times weekly (i.e., from 1 mcg 3 times weekly to 2 mcg 3 times weekly) at intervals of 4 weeks.117 At any time during therapy, the administered dose may be decreased by 2 mcg.117 If dosage reduction is needed in a patient receiving 1 or 2 mcg 3 times weekly, paricalcitol therapy may be withheld as needed and resumed when appropriate.117
If hypercalcemia is observed, the dosage of paricalcitol should be reduced or therapy withheld until the concentration has normalized.117
The initial dosage of IV paricalcitol for the prevention and treatment of secondary hyperparathyroidism in patients with stage 5 CKD is 0.04-0.1 mcg/kg (2.8-7 mcg) at dialysis (no more frequently than every other day).110 The manufacturer states that dosage of paricalcitol should be adjusted according the patient's iPTH concentrations with the goal of reducing iPTH concentrations to no more than 1.5-3 times the upper limit of normal.110 If response is inadequate (i.e., iPTH concentration increases, remains the same, or is not reduced by at least 30%), the manufacturer states that dosage of paricalcitol may be increased by 2-4 mcg per dose at 2- to 4-week intervals.110 The manufacturer states that dosage of paricalcitol should be maintained in patients whose iPTH concentrations have decreased by more than 30 to less than 60% of baseline values or in those with iPTH concentrations 1.5-3 times the upper limit of normal.110 Dosage of paricalcitol should be reduced as iPTH concentrations decline in response to therapy; if iPTH concentrations decrease by more than 60%, the dosage of paricalcitol should be reduced.110 If serum calcium concentrations are elevated, or the serum calcium (in mg/dL) times serum phosphorus (in mg/dL) product (Ca × P) exceeds 75, dosage of paricalcitol should be reduced immediately or therapy withheld.110 Once these parameters have normalized, therapy can be reinitiated at a lower dosage.110 In patients receiving a calcium-containing phosphate binder, the dosage of the phosphate binder should be reduced or withheld; alternatively, the patient can be switched to a non-calcium-containing phosphate binder.110
In the clinical studies used to establish safety and efficacy of paricalcitol, adults received an initial dosage of 0.04 mcg/kg given 3 times weekly; dose was then increased by 0.04 mcg/kg every 2 weeks until the iPTH concentrations were reduced by 30% or declined to less than 100 pg/mL, the fifth dose escalation reached 0.24 mcg/kg, the serum calcium times serum phosphorous product (Ca × P) was more than 75 within any 2-week period, or serum calcium concentrations were greater than 11.5 mg/dL at any time.110,111,113,116 In these studies, dose of paricalcitol was reduced by 0.04 mcg/kg if iPTH concentrations decreased to less than 100 pg/mL, serum calcium concentrations were greater than 11.5 mg/dL, or serum calcium times serum phosphorus product (Ca × P) exceeded 75.111,113 Dose of paricalcitol was maintained when PTH concentrations decreased by 30% or more (but remained above 100 pg/mL), serum calcium concentrations were less than 11.5 mg/dL, and the serum calcium times serum phosphorus product was acceptable (75 or less).113
In a clinical study that evaluated the safety and efficacy of paricalcitol in children 5-19 years of age with end-stage renal disease (ESRD) on hemodialysis, pediatric patients with baseline iPTH concentrations less than 500 pg/mL received an initial dosage of 0.04 mcg/kg administered 3 times weekly while those with baseline iPTH concentrations of at least 500 pg/mL received an initial dosage of 0.08 mcg/kg administered 3 times weekly.110 The initial dose was then adjusted in increments of 0.04 mcg/kg based on serum concentrations of iPTH, calcium, and calcium times serum phosphorous product (Ca × P).110 The mean dose in this study was 4.6 mcg (range: 0.8-9.6 mcg).110