Drug Interactions between aspirin / caffeine / dihydrocodeine 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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

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.

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.