Drug Interactions between dofetilide and sodium polystyrene sulfonate

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.

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.