Calciwin

Calcitriol Injection IV

1mcg/ml

Features:

Calciwin (calcitriol) is the active form of vitamin D₃ (cholecalciferol). The natural or endogenous supply of vitamin D in man mainly depends on ultraviolet light for conversion of 7-dehydrocholesterol to vitamin D₃ in the skin. Vitamin D₃ must be metabolically activated in the liver and the kidney before it is fully active on its target tissues.

Benefits:

The known sites of action of Calciwin (calcitriol) are intestine, bone, kidney and parathyroid gland. Calciwin (calcitriol) is the most active known form of vitamin D₃ in stimulating intestinal calcium transport. Calciwin (calcitriol) has been shown to stimulate intestinal calcium absorption. In bone, calcitriol, in conjunction with parathyroid hormone, stimulates resorption of calcium; and in the kidney, calcitriol increases the tubular reabsorption of calcium. Calciwin (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.

Indications & Usage:

Calciwin (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.

Contraindications:

Calciwin (calcitriol injection) should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Calciwin (calcitriol injection) is contraindicated in patients with previous hypersensitivity to calcitriol or any of its excipients.

Warnings:

Since calcitriol is the most potent metabolite of vitamin D available, prescription-based doses of vitamin D and its derivatives should be withheld or used with caution during treatment to avoid the risk of hypercalcemia.

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 OVERDOSAGE). 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 mg²/dL². Radiographic evaluation of suspect anatomical regions may be useful in the early detection of this condition.

Precautions:

General

Excessive dosage of Calciwin (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.

Calciwin should be given cautiously to patients on digitalis, because hypercalcemia in such patients may precipitate cardiac arrhythmias.

Drug Interactions:

Concomitant use of magnesium-containing preparations should be used with caution or avoided since such use may lead to the development of hypermagnesemia.

Corticosteroids with glucocorticoid activity may counteract the bone and mineral metabolism effects of vitamin D analogues.
Cytochrome P450 enzyme-inducing anticonvulsants such as carbamazepine, phenobarbital and phenytoin may reduce the effects of vitamin D because they increase vitamin D catabolism.

Adverse Reactions:

Adverse effects of Calciwin (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:

Early

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

Late

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, nephrocalcinosis, sensory disturbance, dehydration, apathy, and, rarely, overt psychosis. Occasional mild pain on injection has been observed.

Over Dose:

Administration of Calciwin (calcitriol injection) to patients in excess of their requirements can cause hypercalcemia, hypercalciuria and hyperphosphatemia. High intake of calcium and phosphate concomitant with Calcijex may lead to similar abnormalities (see WARNINGS, PRECAUTIONS and ADVERSE REACTIONS).

Dosage & Administrations:

Calciwin is for intravenous injection only.

The optimal dose of Calciwin (calcitriol injection) must be carefully determined for each patient.

The effectiveness of Calciwin 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 Calciwin, depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism, is 1 mcg (0.02 mcg/kg) to 2 mcg administered intravenously 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 Calciwin 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.