Drug Interactions between Lokelma and Tarpeyo

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

ADJUST DOSING INTERVAL: Because sodium zirconium cyclosilicate can transiently increase gastric pH, it may affect the absorption of coadministered medications that exhibit pH-dependent solubility. Altered efficacy or safety of these medications may occur when they are administered too close to the dosing of sodium zirconium cyclosilicate. According to the product labeling, 39 drugs were tested to determine potential interactions with sodium zirconium cyclosilicate. Drugs that did not show an in vitro interaction with sodium zirconium cyclosilicate were allopurinol, apixaban, aspirin, captopril, cyclosporine, digoxin, ethyl estradiol, lisinopril, magnesium, metformin, phenytoin, prednisone, propranolol, quinapril, spironolactone, and ticagrelor. Of the 23 drugs that showed an in vitro interaction, nine were subsequently tested in healthy volunteers. Losartan, glipizide, and levothyroxine did not demonstrate an in vivo interaction with sodium zirconium cyclosilicate. However, an increase in systemic exposure was observed for weak acids such as furosemide and atorvastatin when coadministered with sodium zirconium cyclosilicate, while a decrease in systemic exposure was observed for weak bases such as dabigatran.

MANAGEMENT: In general, concomitant oral medications should be administered at least 2 hours before or 2 hours after sodium zirconium cyclosilicate. Separation of dosing times is not needed if it has been determined that the concomitant medication does not exhibit pH-dependent solubility.