What are the potential drug interactions with cefpodoxime (Cefpodoxime proxetil)?

From the Guidelines

Cefpodoxime can interact with several medications and substances, requiring careful consideration when prescribed, and it is essential to prioritize caution to minimize potential adverse effects on morbidity, mortality, and quality of life. When considering the use of cefpodoxime, it is crucial to be aware of potential interactions with other medications.

• Antacids containing aluminum or magnesium and H2 blockers may reduce cefpodoxime absorption, so separate administration by at least 2 hours is recommended 1.
• Probenecid increases cefpodoxime blood levels by reducing renal excretion, which can be used therapeutically but requires monitoring 1.
• Cefpodoxime may reduce the effectiveness of oral contraceptives, so additional contraceptive methods are recommended during treatment.
• When combined with nephrotoxic drugs like aminoglycosides or loop diuretics, there's an increased risk of kidney damage 1.
• Alcohol consumption should be avoided during treatment as it may cause disulfiram-like reactions with flushing, headache, and nausea.
• Cefpodoxime can also alter INR values in patients on warfarin, requiring more frequent monitoring. These interactions occur because cefpodoxime, as a cephalosporin antibiotic, affects drug metabolism pathways and competes for protein binding and elimination routes with other medications. It is also important to consider the patient's medical history, including recent antibiotic use, to minimize the risk of treatment failure or resistant pathogens 1. The most recent and highest quality study 1 provides guidance on the use of cefpodoxime in the treatment of acute bacterial rhinosinusitis, emphasizing the importance of careful consideration of potential interactions and individual patient factors to optimize treatment outcomes and minimize adverse effects.

From the FDA Drug Label

Drug Interactions Antacids Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or H2 blockers reduces peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%, respectively. The rate of absorption is not altered by these concomitant medications. Oral anti-cholinergics (e.g., propantheline) delay peak plasma levels (47% increase in Tmax), but do not affect the extent of absorption (AUC). Probenecid As with other beta-lactam antibiotics, renal excretion of cefpodoxime was inhibited by probenecid and resulted in an approximately 31% increase in AUC and 20% increase in peak cefpodoxime plasma levels Nephrotoxic drugs Although nephrotoxicity has not been noted when cefpodoxime proxetil was given alone, close monitoring of renal function is advised when cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.

Key Interactions:

• Antacids: reduce peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%
• Oral anti-cholinergics: delay peak plasma levels by 47% increase in Tmax
• Probenecid: increase AUC by 31% and peak cefpodoxime plasma levels by 20%
• Nephrotoxic drugs: close monitoring of renal function is advised when administered concomitantly with cefpodoxime proxetil 2

From the Research

Drug Interaction with Cefpodoxime

• Cefpodoxime is a semi-synthetic, third-generation cephalosporin with a broad spectrum of antibacterial activity, effective against both Gram-negative and Gram-positive bacteria 3, 4.
• The drug is available as a prodrug, cefpodoxime proxetil, which is absorbed readily from the gut and reaches adequate levels in most body fluids 3.
• Cefpodoxime proxetil can interact with other drugs, such as antacids and H2 receptor antagonists, which can affect its absorption and pharmacokinetics 5, 6.

Interaction with Antacids and H2 Receptor Antagonists

• The dissolution of cefpodoxime proxetil is pH-dependent, and the presence of antacids like aluminum magnesium hydroxide can reduce its absorption 5.
• H2 receptor antagonists, such as famotidine, can also decrease the absorption of cefpodoxime proxetil 5, 6.
• In vitro studies have shown that cefpodoxime proxetil can form complexes with H2 receptor antagonists, such as ranitidine, famotidine, and cimetidine, which can affect its availability 6.

Pharmacokinetics and Drug-Drug Interactions

• The pharmacokinetics of cefpodoxime can be affected by various factors, including renal function and drug-drug interactions 7.
• The drug exposure of cefpodoxime can be reduced in patients undergoing hemodialysis, and its renal clearance can be lower in pediatric patients compared to adults 7.
• Cefpodoxime can interact with other drugs, and its plasma concentrations can be affected by the presence of other medications 7.