Calcitriol is administered orally, usually in a single daily dose, or by IV injection, usually 3 times weekly.
During therapy with calcitriol, dosage depends on the nature and severity of the patient's hypocalcemia and must be individualized to maintain serum calcium concentrations of 9-10 mg/dL. The manufacturers recommend that serum calcium concentrations be measured at least twice weekly during initial dosage adjustments and after subsequent dosage changes; however, some clinicians recommend that serum calcium concentrations be measured at least weekly for the first 12 weeks of therapy and monthly after stabilization of dosage.
Nephrology experts state that the optimal intact parathyroid hormone (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
For the management of hypocalcemia and resultant metabolic bone disease in patients with chronic renal failure undergoing dialysis, the usual initial adult oral dosage of calcitriol is 0.25 mcg daily. Some patients with normal or slightly reduced serum calcium concentrations require only 0.25 mcg every other day. If adequate clinical and biochemical responses are not obtained with the initial dosage, the dosage may be increased by 0.25 mcg daily at 4- to 8-week intervals. If hypercalcemia occurs, calcitriol should be withheld immediately, a low-calcium diet instituted, calcium supplements withdrawn, and serum calcium concentrations determined daily; when normocalcemia ensues (generally in 2-7 days), the drug can be reinstituted at a dosage that is 0.25 mcg daily less than that which induced hypercalcemia.101 Most patients undergoing hemodialysis require oral calcitriol dosages of 0.5-1 mcg daily.
In children undergoing hemodialysis†, oral calcitriol dosages of 0.25-2 mcg daily have been used to increase serum calcium and decrease PTH concentrations.
For the management of hypocalcemia in patients with chronic renal failure undergoing hemodialysis, the manufacturer states that the initial adult IV dosage of calcitriol is 1 mcg (0.02 mcg/kg) to 2 mcg given 3 times weekly (approximately every other day), depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism.100 Initial dosages have ranged from 0.5-4 mcg 3 times weekly.100 The drug may be administered IV by rapid injection through the catheter at the end of a session of hemodialysis. If adequate clinical and biochemical responses are not obtained with the initial dosage, the dose given 3 times weekly may be increased by 0.5-1 mcg at 2- to 4-week intervals.100 The manufacturer states that calcitriol dosage should be increased if response is inadequate (i.e., the PTH concentration remains unchanged, is increasing, or is not reduced by at least 30%).100 The manufacturer states that dosage of calcitriol should be maintained in patients whose PTH concentration has decreased more than 30% but less than 60% or in whom the PTH concentration is 1.5-3 times the upper limit of normal.100 Dosage should be reduced if the PTH concentration decreases by more than 60%.100 If hypercalcemia occurs during dosage titration or if the serum calcium times serum phosphorus product (Ca × P) exceeds 70 mg2/dL2, calcitriol should be withheld immediately; when normocalcemia ensues, the drug can be reinstituted at a lower dosage.100 Dosage reduction may be required as PTH concentrations decrease in response to therapy.100 Most patients require IV calcitriol dosages of 0.5-3 mcg (0.01-0.05 mcg/kg) 3 times weekly.
For the management of secondary hyperparathyroidism and resultant metabolic bone disease in adults and pediatric patients 3 years of age and older with moderate to severe CKD (creatinine clearance of 15-55 mL/minute, corrected for surface area in children) not yet on dialysis, the usual initial oral dosage of calcitriol is 0.25 mcg once daily. If necessary, the dosage may be increased to 0.5 mcg once daily. If hypercalcemia occurs at a dosage of 0.5 mcg daily, the dosage should be reduced to 0.25 mcg daily; if hypercalcemia occurs at a dosage of 0.25 mcg daily, the drug should be withheld.101 Calcium supplements also should be reduced or discontinued.101 When normocalcemia ensues, calcitriol may be reinstituted at a dosage of 0.25 mcg daily if the previous dosage was 0.5 mcg daily, or at a dosage of 0.25 mcg every other day if the previous dosage was 0.25 mcg daily.101 If hypercalcemia is persistent at the reduced dosage and serum PTH concentrations are normal, calcitriol should be discontinued and the patient should be monitored after 3 months.101
For predialysis pediatric patients younger than 3 years of age, the usual initial oral dosage of calcitriol is 0.01-0.015 mcg/kg once daily.
Hypoparathyroidism and Pseudohypoparathyroidism
For the management of hypoparathyroidism and pseudohypoparathyroidism in adults and children 1 year of age and older, the usual initial oral dosage of calcitriol is 0.25 mcg daily. If adequate clinical and biochemical responses are not obtained with the initial dosage, the dosage may be increased at 2- to 4-week intervals. If hypercalcemia occurs, calcitriol should be withheld immediately, a low-calcium diet instituted, calcium supplements withdrawn, and serum calcium concentrations determined daily; when normocalcemia ensues (generally in 2-7 days), the drug can be reinstituted at a dosage that is 0.25 mcg daily less than that which induced hypercalcemia.101 Most adults and children 6 years of age and older require oral calcitriol dosages of 0.5-2 mcg daily. Most children 1-5 years of age with hypoparathyroidism require oral calcitriol dosages of 0.25-0.75 mcg daily; because of the limited number of children younger than 6 years of age who have received calcitriol for the management of pseudohypoparathyroidism, specific dosage recommendations for these children do not currently exist. A pediatric oral dosage of 0.04-0.08 mcg/kg daily has also been used.
In children and a few adults with vitamin D-dependent rickets†, an oral calcitriol dosage of 1 mcg daily has been used to control serum calcium and treat rickets or osteomalacia. In 2 adults with unusual resistance to calcitriol therapy, 12-17 mcg daily was needed to maintain normocalcemia.
In a few patients with familial hypophosphatemia† (vitamin D-resistant rickets), 2.1 mcg of oral calcitriol daily increased serum calcium concentrations. Oral phosphate salts may be administered concomitantly.
To manage hypocalcemia in premature infants†, 1 mcg of oral calcitriol daily has been used during the first 5 days of life. To control hypocalcemic tetany in premature infants†, some clinicians have used an IV calcitriol dosage of 0.05 mcg/kg daily for 5-12 days.