DRUG INTERACTIONS Drug Interactions
Specific drug interaction studies have not been conducted. Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins; therefore, it may impair intestinal absorption of doxercalciferol. Magnesium-containing antacids and Hectorol® should not be used concomitantly because such use may lead to the development of hypermagnesemia (see WARNINGS). The use of mineral oil or other substances that may affect absorption of fat may influence the absorption and availability of Hectorol®. Although not examined specifically, enzyme inducers (such as glutethimide and phenobarbital) may affect the 25-hydroxylation of Hectorol® and may necessitate dosage adjustments. Cytochrome P450 inhibitors (such as ketoconazole and erythromycin) may inhibit the 25-hydroxylation of Hectorol®. Hence, formation of the active Hectorol® moiety may be hindered.
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OVERDOSAGE
Administration of Hectorol® to patients in excess doses can cause hypercalcemia, hypercalciuria, hyperphosphatemia, and oversuppression of PTH secretion leading in certain cases to adynamic bone disease. High intake of calcium and phosphate concomitant with Hectorol® may lead to similar abnormalities. High levels of calcium in the dialysate bath may contribute to hypercalcemia.
Treatment of Hypercalcemia and Overdosage
General treatment of hypercalcemia (greater than 1 mg/dL above the upper limit of the normal range in dialysis patients;>10.7 mg/dL in pre-dialysis patients) consists of immediate suspension of Hectorol® therapy, institution of a low calcium diet, and withdrawal of calcium supplements. Serum calcium levels should be determined at least weekly until normocalcemia ensues. Hypercalcemia usually resolves in 2 to 7 days. When serum calcium levels have returned to within normal limits, Hectorol® therapy may be reinstituted at a dose that is lower (at least 2.5 mcg in dialysis patients and 0.5 mcg in pre-dialysis patients) than prior therapy. In dialysis patients, serum calcium levels should be obtained weekly after all dosage changes and during subsequent dosage titration. Persistent or markedly elevated serum calcium levels may be corrected by dialysis against a reduced calcium or calcium-free dialysate.
Treatment of Accidental Overdosage of Doxercalciferol
The treatment of acute accidental overdosage of Hectorol® should consist of general supportive measures. If drug ingestion is discovered within a relatively short time (10 minutes), induction of emesis or gastric lavage may be of benefit in preventing further absorption. If drug ingestion is discovered later than 10 minutes post-ingestion, the administration of mineral oil may promote its fecal elimination. Serial serum electrolyte determinations (especially calcium), rate of urinary calcium excretion, and assessment of electrocardiographic abnormalities due to hypercalcemia should be obtained. Such monitoring is critical in patients receiving digitalis. Discontinuation of supplemental calcium and institution of a low calcium diet are also indicated in accidental overdosage. If persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives that may be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis. Also, one may consider dialysis against a calcium-free dialysate.
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