Drug Interactions
Cholestyramine
Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins; as such it may impair intestinal absorption of calcitriol (see WARNINGS and PRECAUTIONS: General).
Phenytoin/Phenobarbital
The coadministration of phenytoin or phenobarbital will not affect plasma concentrations of calcitriol, but may reduce endogenous plasma levels of 25(OH)D3 by accelerating metabolism. Since blood level of calcitriol will be reduced, higher doses of calcitriol may be necessary if these drugs are administered simultaneously.
Thiazides
Thiazides are known to induce hypercalcemia by the reduction of calcium excretion in urine. Some reports have shown that the concomitant administration of thiazides with calcitriol causes hypercalcemia. Therefore, precaution should be taken when coadministration is necessary.
Digitalis
Calcitriol dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcemia in such patients may precipitate cardiac arrhythmias (see PRECAUTIONS: General).
Ketoconazole
Ketoconazole may inhibit both synthetic and catabolic enzymes of calcitriol. Reductions in serum endogenous calcitriol concentrations have been observed following the administration of 300 mg/day to 1200 mg/day ketoconazole for a week to healthy men. However, in vivo drug interaction studies of ketoconazole with calcitriol have not been investigated.
Corticosteroids
A relationship of functional antagonism exists between vitamin D analogues, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption.
Phosphate-Binding Agents
Since calcitriol also has an effect on phosphate transport in the intestine, kidneys and bones, the dosage of phosphate-binding agents must be adjusted in accordance with the serum phosphate concentration.
Vitamin D
Since calcitriol is the most potent active metabolite of vitamin D3, pharmacological doses of vitamin D and its derivatives should be withheld during treatment with calcitriol to avoid possible additive effects and hypercalcemia (see WARNINGS).
Calcium Supplements: Uncontrolled intake of additional calcium-containing preparations should be avoided (see PRECAUTIONS: General).
Magnesium
Magnesium-containing preparations (eg, antacids) may cause hypermagnesemia and should therefore not be taken during therapy with calcitriol by patients on chronic renal dialysis.
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term studies in animals have not been conducted to evaluate the carcinogenic potential of calcitriol. Calcitriol is not mutagenic in vitro in the Ames Test, nor is it genotoxic in vivo in the Mouse Micronucleus Test. No significant effects of calcitriol on fertility and/or general reproductive performances were observed in a Segment I study in rats at doses of up to 0.3 mcg/kg (approximately 3 times the maximum recommended dose based on body surface area).
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