What is the recommended dose of Cefixime (a cephalosporin antibiotic) for an elderly patient with potential Impaired renal function?

Cefixime Dosing in Elderly Patients

For elderly patients with normal renal function (creatinine clearance ≥60 mL/min), use the standard adult dose of 400 mg daily; however, if creatinine clearance is 21-59 mL/min, reduce to 260 mg daily (13 mL of 200 mg/5 mL suspension), and if creatinine clearance is ≤20 mL/min, reduce to 200 mg daily (10 mL of 100 mg/5 mL suspension or 4.4 mL of 200 mg/5 mL suspension). 1

Standard Dosing for Elderly Patients

• The FDA-approved adult dose of cefixime is 400 mg daily, which can be administered as a single daily dose without regard to food 1
• No dose adjustment is required based on age alone in elderly patients with preserved renal function 1, 2
• Pharmacokinetic studies demonstrate that elderly patients achieve comparable peak serum concentrations (5.68 mg/L) to younger subjects (4.74 mg/L) after repeated dosing 2

Critical Consideration: Renal Function Assessment

The key determinant for dosing in elderly patients is creatinine clearance, not chronological age, as elderly patients frequently have age-related decline in renal function even with normal serum creatinine 1, 3

Why This Matters:

• Cefixime elimination half-life increases from 3.73 hours in normal subjects to 12-14 hours in patients with creatinine clearance <20 mL/min 3
• Serum area under the curve (AUC) values are significantly higher in elderly patients (49.5 mg·h/L) compared to young subjects (34.9 mg·h/L), primarily due to reduced renal clearance 2
• Drug accumulation occurs with repeated dosing if renal impairment is not recognized 4, 5

Dose Adjustments for Renal Impairment

The FDA provides specific dosing recommendations based on creatinine clearance 1:

Creatinine Clearance ≥60 mL/min:

• Use standard dose: 400 mg daily 1
• No adjustment necessary 1

Creatinine Clearance 21-59 mL/min:

• Reduce to 260 mg daily (13 mL of 200 mg/5 mL suspension) 1
• This represents approximately 65% of the standard dose 1

Creatinine Clearance ≤20 mL/min:

• Reduce to 200 mg daily 1
• Can be administered as 10 mL of 100 mg/5 mL suspension or 4.4 mL of 200 mg/5 mL suspension 1
• This represents 50% of the standard dose 1

Hemodialysis or Peritoneal Dialysis:

• Use the same dose as creatinine clearance ≤20 mL/min (200 mg daily) 1
• Neither hemodialysis nor peritoneal dialysis removes significant amounts of cefixime from the body 1, 6, 5
• No supplemental doses are necessary after dialysis 5

Pharmacokinetic Rationale

The dose reductions are based on well-established pharmacokinetic alterations in renal impairment 3, 5:

• Renal clearance decreases proportionally with creatinine clearance, with a significant linear correlation (P<0.05) between cefixime clearance and creatinine clearance 3, 2
• In severe renal insufficiency (creatinine clearance <20 mL/min), elimination half-life is prolonged to 11-14 hours compared to 3.7 hours in normal subjects 4, 3
• Peak serum concentrations are slightly increased and occur later (8 hours vs. 2.8 hours) in patients with severe renal impairment 4
• Despite reduced renal clearance, urinary concentrations remain above the MIC for most urinary tract pathogens for up to 24 hours, even in severe renal insufficiency 5

Clinical Efficacy Considerations

• Cefixime maintains therapeutic efficacy at reduced doses in renal impairment because the drug accumulates to compensate for decreased clearance 3, 5
• The 50% bioavailability of oral cefixime is not affected by food, allowing flexible administration 6
• Protein binding (70%) remains constant across different degrees of renal function 6

Important Caveats

Avoid Common Pitfalls:

• Do not assume normal renal function based solely on serum creatinine in elderly patients, as age-related muscle mass loss can mask renal impairment 2
• Calculate creatinine clearance using the Cockcroft-Gault equation or measure it directly to guide dosing 1
• The preferred suspension concentration for patients with renal dysfunction is 200 mg/5 mL to minimize volume and improve accuracy 1

Monitoring:

• Elderly patients with any degree of renal insufficiency should be monitored for adverse effects, particularly gastrointestinal symptoms (diarrhea occurs in 16% of patients) 1
• Reconstituted suspension remains stable for 14 days at room temperature or refrigerated 1

Special Populations:

• In elderly patients with cirrhosis, no dosage adjustment is needed despite a twofold increase in elimination half-life (approximately 6.5 hours), as hepatic clearance compensates 6