Calcitriol (Calcitriol) Injection is synthetically manufactured Calcitriol (Calcitriol) and is available as a sterile, isotonic, clear, colorless to yellow, aqueous solution for intravenous injection. Calcitriol (Calcitriol) Injection is available in 1 mL ampules. Each 1 mL contains Calcitriol (Calcitriol) 1 mcg; polysorbate 20, 4 mg; edetate disodium dehydrate 1.1 mg; sodium phosphate dibasic 7.6 mg; sodium phosphate monobasic 1.8 mg; sodium chloride 1.5 mg; sodium ascorbate 10 mg. pH 6.6 (5.9 - 7.0).

Calcitriol (Calcitriol) is a crystalline compound which occurs naturally in humans. It is soluble in organic solvents but relatively insoluble in water. Calcitriol (Calcitriol) is chemically designated (5Z,7E)-9, 10-secocholesta-5,7,10(19)-triene-1-(alpha),3 (beta),25-triol and has the following structural formula:

Molecular Formula: CHO

The other names frequently used for Calcitriol (Calcitriol) are 1(alpha),25-dihydroxycholecalciferol, 1(alpha),25-dihydroxyvitamin D, 1,25-DHCC, 1,25(OH)D and 1,25-diOHC.

Calcitriol (Calcitriol) is the active form of Vitamin D (cholecalciferol). The natural or endogenous supply of vitamin D in man mainly depends on ultraviolet light for conversion of 7-dehydrocholesterol to vitamin D in the skin. Vitamin D must be metabolically activated in the liver and the kidney before it is fully active on its target tissues. The initial transformation is catalyzed by a vitamin D-25-hydroxylase enzyme present in the liver, and the product of this reaction is 25-(OH)D (calcifediol). The latter undergoes hydroxylation in the mitochondria of kidney tissue, and this reaction is activated by the renal 25-hydroxyvitamin D-1-(alpha)-hydroxylase to produce 1,25-(OH)D (Calcitriol (Calcitriol) ), the active form of vitamin D.

The known sites of action of Calcitriol (Calcitriol) are intestine, bone, kidney and parathyroid gland. Calcitriol (Calcitriol) is the most active known form of vitamin D in stimulating intestinal calcium transport. In acutely uremic rats, Calcitriol (Calcitriol) has been shown to stimulate intestinal calcium absorption. In bone, Calcitriol (Calcitriol) , in conjunction with parathyroid hormone, stimulates resorption of calcium; and in the kidney, Calcitriol (Calcitriol) increases the tubular reabsorption of calcium. and studies have shown that Calcitriol (Calcitriol) directly suppresses secretion and synthesis of PTH. A vitamin D-resistant state may exist in uremic patients because of the failure of the kidney to adequately convert precursors to the active compound, Calcitriol (Calcitriol) .

Calcitriol (Calcitriol) when administered by bolus injection is rapidly available in the blood stream. Vitamin D metabolites are known to be transported in blood, bound to specific plasma proteins. The pharmacologic activity of an administered dose of Calcitriol (Calcitriol) is about 3 to 5 days. Two metabolic pathways for Calcitriol (Calcitriol) have been identified, conversion to 1,24,25-(OH)D and to calcitroic acid.

Calcitriol (Calcitriol) Injection is indicated in the management of hypocalcemia in patients undergoing chronic renal dialysis. It has been shown to significantly reduce elevated parathyroid hormone levels. Reduction of PTH has been shown to result in an improvement in renal osteodystrophy.

Calcitriol (Calcitriol) Injection should not be given to patients with hypercalcemia or evidence of vitamin D toxicity.

Since Calcitriol (Calcitriol) is the most potent metabolite of vitamin D available, vitamin D and its derivatives should be withheld during treatment.

A non-aluminum phosphate-binding compound should be used to control serum phosphorus levels in patients undergoing dialysis.

Overdosage of any form of vitamin D is dangerous (see also ). Progressive hypercalcemia due to overdosage of vitamin D and its metabolites may be so severe as to require emergency attention. Chronic hypercalcemia can lead to generalized vascular calcification, nephrocalcinosis and other soft-tissue calcification. The serum calcium times phosphate (Ca x P) product should not be allowed to exceed 70. Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition.

Excessive dosage of Calcitriol (Calcitriol) Injection induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium and phosphorus should be determined at least twice weekly. Should hypercalcemia develop, the drug should be discontinued immediately.

Calcitriol (Calcitriol) Injection should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.

Serum calcium, phosphorus, magnesium and alkaline phosphatase and 24-hour urinary calcium and phosphorus should be determined periodically. During the initial phase of the medication, serum calcium and phosphorus should be determined more frequently (twice weekly).

Adynamic bone disease may develop if PTH levels are suppressed to abnormal levels. If biopsy is not being done for other (diagnostic) reasons, PTH levels may be used to indicate the rate of bone turnover. If PTH levels fall below recommended target range (1.5 to 3 times the upper limit of normal), in patients treated with Calcitriol (Calcitriol) Injection, the Calcitriol (Calcitriol) Injection dose should be reduced or therapy discontinued. Discontinuation of Calcitriol (Calcitriol) Injection therapy may result in rebound effect, therefore, appropriate titration downward to a maintenance dose is recommended.

Adverse effects of Calcitriol (Calcitriol) Injection are, in general, similar to those encountered with excessive vitamin D intake. The early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia include:

Weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste.

Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis. Occasional mild pain on injection has been observed.

Administration of Calcitriol (Calcitriol) Injection to patients in excess of their requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. High intake of calcium and phosphate concomitant with Calcitriol (Calcitriol) Injection may lead to similar abnormalities.

The optimal dose of Calcitriol (Calcitriol) Injection must be carefully determined for each patient.

The effectiveness of Calcitriol (Calcitriol) Injection therapy is predicated on the assumption that each patient is receiving an adequate and appropriate daily intake of calcium. The RDA for calcium in adults is 800 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.

The recommended initial dose of Calcitriol (Calcitriol) Injection, depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism, is 1 mcg (0.02 mcg/kg) to 2 mcg administered three times weekly, approximately every other day. Doses as small as 0.5 mcg and as large as 4 mcg three times weekly have been used as an initial dose. If a satisfactory response is not observed, the dose may be increased by 0.5 to 1 mcg at two to four week intervals. During this titration period, serum calcium and phosphorus levels should be obtained at least twice weekly. If hypercalcemia or a serum calcium times phosphate product greater than 70 is noted, the drug should be immediately discontinued until these parameters are appropriate. Then, the Calcitriol (Calcitriol) Injection dose should be reinitiated at a lower dose. Doses may need to be reduced as the PTH levels decrease in response to the therapy. Thus, incremental dosing must be individualized and commensurate with PTH, serum calcium and phosphorus levels. The following is a suggested approach in dose titration:

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard unused portion.

Calcitriol (Calcitriol) Injection is supplied as follows:

1 mL Single Dose VialsFor IV Injection Only