Drug Interaction Report

GENERALLY AVOID: The coadministration with H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH may reduce the oral bioavailability of cefpodoxime proxetil and cefuroxime axetil. The proposed mechanism is a pH-dependent reduction in drug dissolution and absorption. In ten healthy volunteers, famotidine 40 mg administered one hour before the ingestion of cefpodoxime proxetil 200 mg led to an approximately 40% reduction in the cefpodoxime peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) compared to when the drug was given alone. Similar results were reported with ranitidine in another study, where cefpodoxime Cmax and AUC decreased by approximately 30%. Likewise, pretreatment with ranitidine plus sodium bicarbonate decreased the Cmax and AUC of cefuroxime by over 40% in six healthy volunteers. The clinical significance of these effects is unknown, but potentially reduced antibiotic efficacy should be considered.

MANAGEMENT: Until further data are available, patients treated with cefpodoxime proxetil or cefuroxime axetil may want to avoid using H2-receptor antagonists, proton pump inhibitors, or other agents that can increase gastric pH. An alternative antibiotic may be considered if these medications cannot be discontinued.

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GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

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GENERALLY AVOID: Coadministration with large amounts of certain fruit juices, including grapefruit, orange and apple, may decrease the oral bioavailability of fexofenadine. The proposed mechanism is inhibition of drug efflux via intestinal organic anion transporting polypeptides (e.g., P-glycoprotein), of which fexofenadine is a substrate. In a five-way crossover study with 10 healthy volunteers, 1/4-strength grapefruit juice, grapefruit juice, orange juice and apple juice (300 mL with drug administration and 150 mL every 1/2 hour for up to 3 hours, total volume 1.2 L) reduced the mean area under the plasma concentration-time curve (AUC) of a 120 mg dose of fexofenadine by 23%, 67%, 72% and 77%, respectively, compared to water. Mean peak plasma concentration (Cmax) was similarly affected. The clinical significance of these changes is unknown. However, results from studies using histamine-induced skin wheals and flares found that the size of wheal and flare was significantly larger when fexofenadine was administered with either grapefruit or orange juices compared to water.

MANAGEMENT: To maximize plasma levels and therapeutic effects, fexofenadine should be taken with water. In addition, patients should refrain from consuming large amounts of grapefruit, orange, or apple juice.

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