Drug Interactions between DDAVP and Vitamin D3

MONITOR: Additive effects and possible toxicity (e.g., hypercalcemia, hypercalciuria, and/or hyperphosphatemia) may occur when patients using vitamin D and/or vitamin D analogs ingest a diet high in vitamin D, calcium, and/or phosphorus. The biologically active forms of vitamin D stimulate intestinal absorption of calcium and phosphorus. This may be helpful in patients with hypocalcemia and/or hypophosphatemia. However, sudden increases in calcium or phosphorus consumption due to dietary changes could precipitate hypercalcemia and/or hyperphosphatemia. Patients with certain disease states, such as impaired renal function, may be more susceptible to toxic side effects like ectopic calcification. On the other hand, if dietary calcium is inadequate for the body's needs, the active form of vitamin D will stimulate osteoclasts to pull calcium from the bones. This may be detrimental in a patient with reduced bone density.

MANAGEMENT: Given the narrow therapeutic index of vitamin D and vitamin D analogs, the amounts of calcium, phosphorus, and vitamin D present in the patient's diet may need to be taken into consideration. Specific dietary guidance should be discussed with the patient and regular lab work should be monitored as indicated. Calcium, phosphorus, and vitamin D levels should be kept within the desired ranges, which may differ depending on the patient's condition. Patients should also be counseled on the signs and symptoms of hypervitaminosis D, hypercalcemia, and/or hyperphosphatemia.

Food may decrease the rate and extent of absorption of desmopressin following oral administration. In 16 healthy, nonsmoking volunteers, administration of a single 400 mcg oral dose of desmopressin concomitantly with a standardized meal (27% fat) resulted in a 52% decrease in the peak plasma concentration (Cmax) of desmopressin and a 43% decrease in systemic exposure (AUC) compared to administration in the fasting state. The Cmax and AUC were still reduced by 46% and 41%, respectively, when desmopressin was administered 1.5 hours after eating. Both feeding regimens prolonged the time to reach peak plasma concentration (Tmax) from 1 hour to 1.5 hours. However, the pharmacodynamic effects of desmopressin were not affected as assessed by urine volume and osmolality for at least 4 hours postdose. The degree of antidiuresis was similar in the absence of food and when the drug was taken with or 1.5 hours after eating. These findings would suggest a fairly minor clinical impact of the interaction in most patients, especially since oral desmopressin is intended for administration at bedtime. Nevertheless, the possibility of food effects should be considered before increasing the dose whenever a diminution of effect is noted. A significant interaction is not expected to occur with the sublingual formulation, since absorption occurs primarily in the oral mucosa, pharynx, and esophagus.