Rocaltrol (Calcitriol) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Cholestyramine

Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins; as such it may impair intestinal absorption of Rocaltrol (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 Rocaltrol 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 Rocaltrol 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 Rocaltrol 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 Rocaltrol 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 D_3, pharmacological doses of vitamin D and its derivatives should be withheld during treatment with Rocaltrol 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 Rocaltrol by patients on chronic renal dialysis.

OVERDOSAGE

Administration of Rocaltrol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. Since calcitriol is a derivative of vitamin D, the signs and symptoms of overdose are the same as for an overdose of vitamin D (see ADVERSE REACTIONS). High intake of calcium and phosphate concomitant with Rocaltrol may lead to similar abnormalities. The serum calcium times phosphate (Ca × P) product should not be allowed to exceed 70 mg²/dL². High levels of calcium in the dialysate bath may contribute to the hypercalcemia (see WARNINGS).

Treatment of Hypercalcemia and Overdosage in Dialysis Patients and Hypoparathyroidism Patients

General treatment of hypercalcemia (greater than 1 mg/dL above the upper limit of the normal range) consists of immediate discontinuation of Rocaltrol therapy, institution of a low-calcium diet and withdrawal of calcium supplements. Serum calcium levels should be determined daily until normocalcemia ensues. Hypercalcemia frequently resolves in 2 to 7 days. When serum calcium levels have returned to within normal limits, Rocaltrol therapy may be reinstituted at a dose of 0.25 mcg/day less than prior therapy. Serum calcium levels should be obtained at least twice weekly after all dosage changes and subsequent dosage titration. In dialysis patients, persistent or markedly elevated serum calcium levels may be corrected by dialysis against a calcium-free dialysate.

Treatment of Hypercalcemia and Overdosage in Predialysis Patients

If hypercalcemia ensues (greater than 1 mg/dL above the upper limit of the normal range), adjust dosage to achieve normocalcemia by reducing Rocaltrol therapy from 0.5 mcg to 0.25 mcg daily. If the patient is receiving a therapy of 0.25 mcg daily, discontinue Rocaltrol until patient becomes normocalcemic. Calcium supplements should also be reduced or discontinued. Serum calcium levels should be determined 1 week after withdrawal of calcium supplements. If serum calcium levels have returned to normal, Rocaltrol therapy may be reinstituted at a dosage of 0.25 mcg/day if previous therapy was at a dosage of 0.5 mcg/day. If Rocaltrol therapy was previously administered at a dosage of 0.25 mcg/day, Rocaltrol therapy may be reinstituted at a dosage of 0.25 mcg every other day. If hypercalcemia is persistent at the reduced dosage, serum PTH should be measured. If serum PTH is normal, discontinue Rocaltrol therapy and monitor patient in 3 months' time.

Treatment of Hyperphosphatemia in Predialysis Patients

If serum phosphorus levels exceed 5.0 mg/dL to 5.5 mg/dL, a calcium-containing phosphate-binding agent (ie, calcium carbonate or calcium acetate) should be taken with meals. Serum phosphorus levels should be determined as described earlier (see PRECAUTIONS: Laboratory Tests). Aluminum-containing gels should be used with caution as phosphate-binding agents because of the risk of slow aluminum accumulation.

Treatment of Accidental Overdosage of Rocaltrol

The treatment of acute accidental overdosage of Rocaltrol should consist of general supportive measures. If drug ingestion is discovered within a relatively short time, induction of emesis or gastric lavage may be of benefit in preventing further absorption. If the drug has passed through the stomach, 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 a low-calcium diet are also indicated in accidental overdosage. Due to the relatively short duration of the pharmacological action of calcitriol, further measures are probably unnecessary. Should, however, persistent and markedly elevated serum calcium levels occur, there are a variety of therapeutic alternatives which may be considered, depending on the patient's underlying condition. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce an appropriate forced diuresis. The use of peritoneal dialysis against a calcium-free dialysate has also been reported.

CONTRAINDICATIONS

Rocaltrol should not be given to patients with hypercalcemia or evidence of vitamin D toxicity. Use of Rocaltrol in patients with known hypersensitivity to Rocaltrol (or drugs of the same class) or any of the inactive ingredients is contraindicated.