Drug Interaction Report

MONITOR: Elevations in serum calcium levels have been observed in patients treated with topical vitamin D analogs. Concomitant use with systemic vitamin D products, calcium supplements, or other agents that can increase serum calcium concentrations such as thiazide diuretics, estrogens, anabolic steroids, and parathyroid hormone or parathyroid hormone analogs may increase the risk of clinically significant hypercalcemia.

MANAGEMENT: Calcium and vitamin D status should be monitored closely when topical vitamin D analogs are used in combination with systemic vitamin D products or other agents that can increase serum calcium levels.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.