What is the preferred route of administration for Cefepime (intravenous (IV) or intramuscular (IM)) in an adult patient with potential impaired renal function?

Cefepime Administration Route: IV is Strongly Preferred

For adult patients with potential impaired renal function, cefepime should be administered intravenously (IV), as this is the FDA-approved and guideline-recommended route that allows for precise dosing adjustments based on creatinine clearance. 1

Primary Recommendation

• IV administration is the standard route for cefepime in hospitalized patients, particularly those with renal impairment who require careful dose titration 1
• The FDA label specifies detailed IV dosing regimens with adjustments for various levels of renal function (CrCL >60,30-60,11-29, <11 mL/min, hemodialysis, and CAPD), but provides no IM dosing guidance 1
• All major clinical practice guidelines for serious infections (HAP/VAP, febrile neutropenia, pneumonia) exclusively recommend IV cefepime administration 2

Renal Impairment Considerations

In patients with impaired renal function, IV administration is essential because:

• Cefepime requires precise dose adjustments based on creatinine clearance, with dosing intervals extending from every 8 hours to every 48 hours depending on renal function 1
• Over 80% of cefepime is renally excreted unchanged, making accumulation a significant risk in renal impairment 3
• Cefepime can cause concentration-related neurotoxicity, especially in critically ill patients with renal failure, requiring careful monitoring and dose adjustment 4
• The elimination half-life increases from 2-2.5 hours in normal renal function to significantly longer periods in renal impairment 3

When IM Might Be Considered (Limited Scenarios)

• IM cefepime is mentioned only as an emergency alternative when vascular access is limited or unavailable 5
• The Surviving Sepsis Campaign guidelines suggest IM administration only if timely establishment of vascular access is not possible 5
• However, no specific IM dosing recommendations exist in the FDA label for cefepime, unlike other antibiotics such as ceftriaxone which has established IM dosing 2, 1

Clinical Dosing Algorithm for Renal Impairment

For patients with CrCL >60 mL/min:

• Standard dosing: 1-2g IV every 8-12 hours depending on infection severity 1

For patients with CrCL 30-60 mL/min:

• Reduce to: 500mg-2g IV every 24 hours (depending on indication) 1

For patients with CrCL 11-29 mL/min:

• Further reduce to: 250mg-2g IV every 24 hours 1

For patients with CrCL <11 mL/min:

• Minimal dosing: 250mg-1g IV every 24 hours 1

For hemodialysis patients:

• 1g on day 1, then 500mg every 24 hours (or 1g every 24 hours for febrile neutropenia), administered after dialysis 1
• Approximately 68% of cefepime is removed during a 3-hour dialysis session 1

Important Caveats

• Neurotoxicity risk increases with accumulation: In critically ill patients with renal failure, maintaining appropriate dosing intervals is critical to prevent concentration-related neurotoxicity 4
• Linear pharmacokinetics: Cefepime exhibits linear pharmacokinetic behavior with no drug accumulation when dosed appropriately for renal function 3, 6
• Protein binding is low (16-19%): This allows wide tissue distribution but also means more free drug is available for renal excretion and potential accumulation 3
• IM absorption is unpredictable: Bioavailability after IM administration in pediatric studies ranged widely from 61-124%, making it unreliable for precise dosing 7

Guideline-Supported IV Dosing Regimens

For hospital-acquired pneumonia:

• 2g IV every 8 hours (standard recommendation) 2

For febrile neutropenia:

• 2g IV every 8 hours for 7 days or until neutropenia resolves 2

For severe infections with Pseudomonas risk:

• 2g IV every 8 hours as part of combination therapy 2