Drug Interactions between ritonavir and sodium zirconium cyclosilicate

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

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.