Drug Interaction Report

MONITOR: Cation exchange resins may increase the risk of precipitating hypokalemia and cardiotoxic effects when administered to a patient also receiving cardiac glycosides. The mechanism is the pharmacologic action of exchange resins (increased potassium excretion).

MANAGEMENT: Serum potassium levels should be closely monitored if these agents must be coadministered.

GENERALLY AVOID: Potassium in foods can bind to the cation exchange resin and interfere with potassium removal in the treatment of hyperkalemia.

MANAGEMENT: Cation exchange resins should not be mixed with orange juice or other foods with a high potassium content.

ADJUST DOSING INTERVAL: Cation exchange resins may bind to other medications that are administered orally. Reduced systemic absorption and therapeutic efficacy may occur. Manufacturers have reported that polystyrene sulfonate exchange resins can decrease the absorption of lithium and levothyroxine. A more recent study found that sodium polystyrene sulfonate binds to many commonly prescribed oral medications. Another potassium-lowering drug, patiromer, has also been found to bind about half of the medications tested, some of which are commonly used in patients who require potassium-lowering drugs.

MANAGEMENT: To minimize the risk of interaction, patients should be advised to separate the dosing of the cation exchange resin from other orally administered medications by at least 3 hours. The dosing interval should be increased to 6 hours for patients with gastroparesis or other conditions resulting in delayed emptying of food from the stomach into the small intestine. Health care professionals should monitor blood levels and/or clinical response to the other medications when appropriate.

ADJUST DOSING INTERVAL: Simultaneous administration of cation-donating preparations may reduce the potassium exchange capability of cation-exchange resins due to binding of the cation to the resin.

MANAGEMENT: Patients should consider separating the times of administration of the cation-exchange resin and any cation-donating preparation (e.g., mineral supplements; antacids; products containing antacids such as didanosine buffered tablets or pediatric oral solution) by several hours if possible.

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.