Tables 3 and 4 include clinically significant drug interactions with doxercalciferol. Table 3: Clinically Significant Drug Interactions with Doxercalciferol Capsules Drugs that May Increase the Risk of Hypercalcemia Clinical Impact Concomitant administration of high doses of calcium-containing preparations or other vitamin D compounds may increase the risk of hypercalcemia. Thiazide diuretics are known to induce hypercalcemia by reducing excretion of calcium in the urine.
Examples Calcium-containing products, other vitamin D compounds or thiazide diuretics Intervention Monitor serum calcium concentrations more frequently and adjust doxercalciferol dose as needed [see Warnings and Precautions ( 5.1 )]. Digitalis Compounds Clinical Impact Doxercalciferol can cause hypercalcemia which can potentiate the risk of digitalis toxicity. Intervention Monitor patients for signs and symptoms of digitalis toxicity and increase frequency of serum calcium monitoring when initiating or adjusting the dose of doxercalciferol in patients receiving digitalis compounds [see Warnings and Precautions ( 5.2 )].
Cytochrome P450 Inhibitors Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Cytochrome P450 inhibitors may inhibit the 25-hydroxylation of doxercalciferol and thus reduce the formation of active doxercalciferol moiety [see Clinical Pharmacology ( 12.3 )]. Examples Ketoconazole and erythromycin Intervention If a patient initiates or discontinues therapy with a cytochrome P450 inhibitor, dose adjustment of doxercalciferol may be necessary.
Monitor intact PTH and serum calcium concentrations closely. Enzyme Inducers Clinical Impact Doxercalciferol is activated by CYP 27 in the liver. Enzyme inducers may affect the 25-hydroxylation of doxercalciferol [see Clinical Pharmacology ( 12.3 )]. Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary.
Monitor intact PTH and serum calcium concentrations closely. Magnesium-containing Products Clinical Impact Concomitant administration of doxercalciferol and high doses of magnesium-containing products may increase the risk of hypermagnesemia. Examples Magnesium-containing products such as antacids Intervention Avoid use of magnesium-containing products and doxercalciferol in patients on chronic renal dialysis. Table 4: Clinically Significant Drug Interactions with Doxercalciferol Capsules Cholestyramine Clinical Impact Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins.
Therefore, it may impair intestinal absorption of doxercalciferol capsules. Intervention Administer doxercalciferol capsules at least 1 hour before or 4 to 6 hours after taking cholestyramine. Mineral Oil or other Substances that May Affect Absorption of Fat Clinical Impact The use of mineral oil or other substances that may affect absorption of fat may influence the absorption and availability of doxercalciferol. Intervention Administer doxercalciferol capsules at least 1 hour before or 4 to 6 hours after taking mineral oil or other substances that may affect absorption of fat.
Cytochrome P450 inhibitors: Formation of the active doxercalciferol moiety may be hindered and may necessitate dosage adjustment. Monitor intact PTH and serum calcium concentrations closely. ( 7 ) Enzyme inducers: Formation of the active doxercalciferol moiety may be affected and may necessitate dosage adjustment. Monitor intact PTH and serum calcium concentrations closely. ( 7 ) Magnesium-containing products: Combined use may cause hypermagnesemia.
Monitor serum magnesium concentrations more frequently and adjust dose as needed. ( 7 ) Cholestyramine: May impair absorption of doxercalciferol capsules. Administer doxercalciferol capsules at least 1 hour before or 4 to 6 hours after taking cholestyramine. ( 7 ) Mineral oil or other substances that may affect absorption of fat: May impair absorption of doxercalciferol capsules. Administer doxercalciferol capsules at least 1 hour before or 4 to 6 hours after taking substances that may affect absorption.
