How should ofloxacin 400 mg twice daily be dose‑adjusted according to creatinine clearance and dialysis modality?

Ofloxacin 400 mg BID Renal Dose Adjustment

For ofloxacin 400 mg twice daily, reduce to 400 mg once every 24 hours when creatinine clearance falls below 50 mL/min, and extend to 400 mg every 48 hours when creatinine clearance is below 20 mL/min. 1

Dosing Algorithm by Creatinine Clearance

CrCl ≥ 50 mL/min

• Standard dosing: 400 mg every 12 hours (no adjustment needed) 1, 2
• Ofloxacin elimination half-life remains 5-7 hours in normal renal function 2

CrCl 20-50 mL/min

• Reduce to: 400 mg every 24 hours 1
• The extended dosing interval of 24 hours prevents drug accumulation while maintaining therapeutic concentrations 1
• Elimination half-life begins to increase proportionally with declining creatinine clearance 1

CrCl < 20 mL/min (Severe Renal Impairment)

• Reduce to: 400 mg every 48 hours 1
• In severe chronic renal failure (CrCl < 20 mL/min), ofloxacin half-life extends dramatically to 23.1 hours (versus 2.9 hours in healthy subjects) 3
• Renal clearance drops from 261 mL/min in healthy subjects to only 8 mL/min in severe CRF 3
• Only 14% of the dose is excreted renally in 24 hours (compared to 92% in healthy subjects) 3

Hemodialysis-Specific Recommendations

Dosing Strategy

• Loading dose: 200 mg orally 4
• Maintenance dose: 100 mg orally once daily, administered at the end of each hemodialysis session 4
• This regimen achieves trough concentrations of 1.6 mg/L and peak concentrations of 3.1 mg/L, which are therapeutically favorable 4

Dialysis Removal Characteristics

• Hemodialysis removes only 21.5% of ofloxacin body burden during a typical session 4
• Dialyzer clearance averages 59.2 mL/min, but this varies by membrane type 4, 5
• Polysulfone membranes remove more drug (49.6% reduction per session) compared to cellulose acetate membranes (45.5% reduction) 5
• Half-life during hemodialysis shortens to 9.9 hours but extends to 38.5 hours between dialysis sessions 4
• Supplemental post-dialysis doses are NOT necessary when using the recommended 100 mg daily regimen 1, 4

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• No supplemental dosing required 1
• CAPD removes only 6-15% of ofloxacin body burden, which is clinically insignificant 1
• Use the same dosing as severe renal impairment (CrCl < 20 mL/min): 400 mg every 48 hours 1

Critical Pharmacokinetic Considerations

Parameters Unchanged by Renal Impairment

• Volume of distribution remains stable regardless of renal function 1, 3
• Peak concentration (Cmax) and time to peak (Tmax) are not significantly altered 1
• Non-renal clearance remains constant across all levels of renal function 1, 3

Parameters Requiring Monitoring

• Elimination half-life correlates linearly with creatinine clearance decline 2
• Over 70% of absorbed ofloxacin is normally excreted unchanged in urine 2
• Minimal metabolism occurs (< 5% as desmethyl ofloxacin and N-oxide metabolites) 2

Common Pitfalls to Avoid

• Do not use standard twice-daily dosing when CrCl < 50 mL/min: This leads to significant drug accumulation (approximately 50% increase in maximal concentration) and potential toxicity 2
• Do not give supplemental doses after hemodialysis when using the recommended 100 mg daily maintenance regimen, as this causes unnecessary accumulation 1, 4
• Consider dialyzer membrane type: Polysulfone membranes remove more ofloxacin than cellulose acetate, though the clinical significance is modest 5
• Reassess renal function during treatment: Acute changes in kidney function require immediate dosing adjustment given the drug's heavy renal dependence 1, 3