Calcitriol - Calcitriol solution

Calcitriol Oral Solution is indicated in the management of secondary hyperparathyroidism and resultant metabolic bone disease in patients with moderate to severe chronic renal failure (Ccr 15 to 55 mL/min) not yet on dialysis. In children, the creatinine clearance value must be corrected for a surface area of 1.73 square meters. A serum iPTH level of ≥ 100 pg/mL is strongly suggestive of secondary hyperparathyroidism.

Calcitriol Oral Solution is indicated in the management of hypocalcemia and the resultant metabolic bone disease in patients undergoing chronic renal dialysis. In these patients, Calcitriol Oral Solution administration enhances calcium absorption, reduces serum alkaline phosphatase levels, and may reduce elevated parathyroid hormone levels and the histological manifestations of osteitis fibrosa cystica and defective mineralization.

Calcitriol Oral Solution is also indicated in the management of hypocalcemia and its clinical manifestations in patients with postsurgical hypoparathyroidism, idiopathic hypoparathyroidism, and pseudohypoparathyroidism.

The optimal daily dose of Calcitriol Oral Solution must be carefully determined for each patient. Calcitriol Oral Solution can be administered as an oral solution (1 mcg/mL). Calcitriol Oral Solution therapy should always be started at the lowest possible dose and should not be increased without careful monitoring of serum calcium.

The effectiveness of Calcitriol Oral Solution therapy is predicated on the assumption that each patient is receiving an adequate but not excessive daily intake of calcium. Patients are advised to have a dietary intake of calcium at a minimum of 600 mg daily. The U.S. RDA for calcium in adults is 800 mg to 1200 mg. To ensure that each patient receives an adequate daily intake of calcium, the physician should either prescribe a calcium supplement or instruct the patient in proper dietary measures.

Because of improved calcium absorption from the gastrointestinal tract, some patients on Calcitriol Oral Solution may be maintained on a lower calcium intake. Patients who tend to develop hypercalcemia may require only low doses of calcium or no supplementation at all.

During the titration period of treatment with Calcitriol Oral Solution, serum calcium levels should be checked at least twice weekly. When the optimal dosage of Calcitriol Oral Solution has been determined, serum calcium levels should be checked every month (or as given below for individual indications). Samples for serum calcium estimation should be taken without a tourniquet.

The recommended initial dose of Calcitriol Oral Solution is 0.25 mcg/day. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease state is not observed, dosage may be increased by 0.25 mcg/day at 4- to 8-week intervals. During this titration period, serum calcium levels should be obtained at least twice weekly, and if hypercalcemia is noted, the drug should be immediately discontinued until normocalcemia ensues (see 

Patients with normal or only slightly reduced serum calcium levels may respond to Calcitriol Oral Solution doses of 0.25 mcg every other day. Most patients undergoing hemodialysis respond to doses between 0.5 and 1 mcg/day.

Calcitriol Oral Solution may normalize plasma-ionized calcium in some uremic patients, yet fail to suppress parathyroid hyperfunction. In these individuals with autonomous parathyroid hyper-function, Calcitriol Oral Solution may be useful to maintain normocalcemia, but has not been shown to be adequate treatment for hyperparathyroidism.

The recommended initial dosage of Calcitriol Oral Solution is 0.25 mcg/day given in the morning. If a satisfactory response in the biochemical parameters and clinical manifestations of the disease is not observed, the dose may be increased at 2- to 4-week intervals. During the dosage titration period, serum calcium levels should be obtained at least twice weekly and, if hypercalcemia is noted, Calcitriol Oral Solution should be immediately discontinued until normocalcemia ensues (see 

Most adult patients and pediatric patients age 6 years and older have responded to dosages in the range of 0.5 mcg to 2 mcg daily. Pediatric patients in the 1- to 5-year age group with hypoparathyroidism have usually been given 0.25 mcg to 0.75 mcg daily. The number of treated patients with pseudohypoparathyroidism less than 6 years of age is too small to make dosage recommendations.

Malabsorption is occasionally noted in patients with hypoparathyroidism; hence, larger doses of Calcitriol Oral Solution may be needed.

The recommended initial dosage of Calcitriol Oral Solution is 0.25 mcg/day in adults and pediatric patients 3 years of age and older. This dosage may be increased if necessary to 0.5 mcg/day.

For pediatric patients less than 3 years of age, the recommended initial dosage of Calcitriol Oral Solution is 10 to 15 ng/kg/day.

Since Calcitriol Oral Solution is believed to be the active hormone which exerts vitamin D activity in the body, adverse effects are, in general, similar to those encountered with excessive vitamin D intake, ie, hypercalcemia syndrome or calcium intoxication (depending on the severity and duration of hypercalcemia) (see 

The early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia include:

In clinical studies on hypoparathyroidism and pseudohypoparathyroidism, hypercalcemia was noted on at least one occasion in about 1 in 3 patients and hypercalciuria in about 1 in 7 patients. Elevated serum creatinine levels were observed in about 1 in 6 patients (approximately one half of whom had normal levels at baseline).

In concurrent hypercalcemia and hyperphosphatemia, soft-tissue calcification may occur; this can be seen radiographically (see 

In patients with normal renal function, chronic hypercalcemia may be associated with an increase in serum creatinine (see 

Hypersensitivity reactions (pruritus, rash, urticaria, and very rarely severe erythematous skin disorders) may occur in susceptible individuals. One case of erythema multiforme and one case of allergic reaction (swelling of lips and hives all over the body) were confirmed by rechallenge.

Calcitriol Oral Solution is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body. Calcitriol oral solution contains 1 mcg/mL of calcitriol. Calcitriol Oral Solution contains butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as antioxidants. Calcitriol oral solution contains caprylic triglycerides. The oral solution contains no additional adjuvants or coloring principles.

Calcitriol is a white, crystalline compound which occurs naturally in humans. It has a calculated molecular weight of 416.65 and is soluble in organic solvents but relatively insoluble in water. Chemically, calcitriol is 9,10-seco(5Z,7E)-5,7,10(19)-cholestatriene-1α, 3β, 25-triol and has the following structural formula:

Man's natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D₃ (cholecalciferol). Vitamin D₃ must be metabolically activated in the liver and the kidney before it is fully active as a regulator of calcium and phosphorus metabolism at target tissues. The initial transformation of vitamin D₃ is catalyzed by a vitamin D₃-25-hydroxylase enzyme (25-OHase) present in the liver, and the product of this reaction is 25-hydroxyvitamin D₃ [25-(OH)D₃]. Hydroxylation of 25-(OH)D₃ occurs in the mitochondria of kidney tissue, activated by the renal 25-hydroxyvitamin D₃-1 alpha-hydroxylase (alpha-OHase), to produce 1,25-(OH)₂D₃ (calcitriol), the active form of vitamin D₃. Endogenous synthesis and catabolism of calcitriol, as well as physiological control mechanisms affecting these processes, play a critical role regulating the serum level of calcitriol. Physiological daily production is normally 0.5 to 1.0 mcg and is somewhat higher during periods of increased bone synthesis (eg, growth or pregnancy).