Drug Interactions between patiromer and Quinidex Extentabs

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

ADJUST DOSING INTERVAL: Patiromer can bind to some orally administered drugs, which may decrease their gastrointestinal absorption and reduce their effectiveness. According to the manufacturer, out of 28 drugs that were tested in in vitro binding studies, 14 did not show an interaction with patiromer (acetylsalicylic acid, allopurinol, amoxicillin, apixaban, atorvastatin, cephalexin, digoxin, glipizide, lisinopril, phenytoin, riboflavin, rivaroxaban, spironolactone, and valsartan). Twelve of the 14 drugs that did show an in vitro interaction were subsequently tested in in vivo studies with healthy volunteers, which revealed no changes in systemic exposure when coadministered with patiromer (amlodipine, cinacalcet, clopidogrel, furosemide, lithium, metoprolol, trimethoprim, verapamil, and warfarin). Patiromer was found to decrease systemic exposure of coadministered ciprofloxacin, levothyroxine, and metformin. However, no significant interaction occurred when patiromer and these drugs were dosed 3 hours apart.

MANAGEMENT: Patiromer should be administered with food at least 3 hours before or 3 hours after other oral medications. Alternatives to patiromer or the other medications should be considered if adequate dosing separation is not possible. Otherwise, clinical response and/or blood levels should be monitored where possible.