Drug Interactions between pramlintide 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.

ADJUST DOSING INTERVAL: Pramlintide slows gastric emptying and may delay the absorption of concomitantly administered oral medications. In a pharmacokinetic study of 24 patients with type 2 diabetes, coadministration with pramlintide (120 mcg) decreased the peak plasma concentration (Cmax) of acetaminophen (1000 mg) by 29% and increased its time to peak plasma concentration (Tmax) based on the time of acetaminophen administration relative to pramlintide injection. Pramlintide significantly increased acetaminophen Tmax (range 48 to 72 minutes) when acetaminophen was administered simultaneously with or up to 2 hours following pramlintide injection, but it had negligible effect when acetaminophen was administered 1 to 2 hours before pramlintide injection.

MANAGEMENT: When rapid onset of a concomitantly administered oral medication is critical to its effectiveness, the medication should be administered at least 1 hour before or 2 hours after pramlintide injection.