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.

ADJUST DOSING INTERVAL: Coadministration with antacids or agents with acid-neutralizing effects 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, 10 mL of magnesium hydroxide-aluminum hydroxide (600 mg-900 mg) administered at 2 hours and at 15 minutes before the ingestion of cefpodoxime proxetil 200 mg led to an approximately 40% reduction in cefpodoxime peak plasma concentration (Cmax) and systemic exposure (AUC) compared to when the antibiotic was administered alone. Similar results were reported with sodium bicarbonate and aluminum hydroxide in another study. 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 should avoid taking antacids or oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) for at least two hours before and after administration of the antibiotic.

ADJUST DOSING INTERVAL: Coadministration with antacids or agents with acid-neutralizing effects 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, 10 mL of magnesium hydroxide-aluminum hydroxide (600 mg-900 mg) administered at 2 hours and at 15 minutes before the ingestion of cefpodoxime proxetil 200 mg led to an approximately 40% reduction in cefpodoxime peak plasma concentration (Cmax) and systemic exposure (AUC) compared to when the antibiotic was administered alone. Similar results were reported with sodium bicarbonate and aluminum hydroxide in another study. 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 should avoid taking antacids or oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) for at least two hours before and after administration of the antibiotic.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

Antacids and some aluminum, calcium, and magnesium salts may decrease the plasma concentrations of H2-receptor antagonists during oral coadministration. The mechanism of interaction is unknown, but may involve reduced oral absorption due to increased gastric pH. Study data vary, with no changes to nearly 60% reductions in systemic exposures (AUCs) reported for cimetidine, famotidine, and ranitidine. The clinical significance has not been established. As a precaution, patients may consider taking H2-receptor antagonists one to two hours before antacids.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of cefpodoxime proxetil tablets. Following a 200 mg dose taken with food, the extent of absorption (mean AUC) was 21% to 33% higher and the mean peak plasma concentration (Cmax) 19% higher than under fasting conditions. Time to peak concentration (Tmax) was not significantly different between fed and fasted states. On the contrary, when a 200 mg dose of the suspension was taken with food, the mean AUC and Cmax were not significantly different than those under fasting conditions, although the rate of absorption was slower with food (48% increase in Tmax ).

MANAGEMENT: To ensure maximal oral absorption, cefpodoxime proxetil tablets should be administered with or immediately after a meal.

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.