Drug Interaction Report

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.

ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

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.