Drug Interactions between baloxavir marboxil and Chewable Calcium with Vitamin D

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

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.

GENERALLY AVOID: Coadministration with foods or medications that contain polyvalent cations such as dairy products, calcium-fortified beverages, certain laxatives, antacids, or oral supplements may decrease the plasma concentrations and therapeutic efficacy of baloxavir. The proposed mechanism is chelation of baloxavir by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. A significant decrease in baloxavir exposure was observed in monkeys when the prodrug, baloxavir marboxil, was coadministered with calcium, aluminum, magnesium, or iron. However, clinical data in humans are lacking.

When baloxavir marboxil was administered with food, baloxavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 48% and 36%, respectively, relative to administration under fasting. These changes are not considered clinically significant.

MANAGEMENT: Baloxavir marboxil may be taken with or without food. However, coadministration with dairy products, calcium-fortified beverages, or polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc) should be avoided.