What is the dosing adjustment for Tamiflu (oseltamivir) in patients with impaired renal function?

Renal Dose Adjustment for Tamiflu (Oseltamivir)

For patients with creatinine clearance 10-30 mL/min, reduce oseltamivir to 75 mg once daily for treatment (instead of twice daily) and to either 30 mg once daily OR 75 mg every other day for prophylaxis. 1, 2, 3

Critical Threshold for Dose Adjustment

• The key creatinine clearance threshold is 30 mL/min - dose adjustment is required when CrCl falls below this level, not at higher values. 1, 2, 3
• Patients with CrCl ≥30 mL/min receive standard dosing without adjustment. 1, 3

Standard Dosing (CrCl ≥30 mL/min)

• Treatment: 75 mg orally twice daily for 5 days 1, 3
• Prophylaxis: 75 mg orally once daily for 10 days after exposure 1, 3

Moderate Renal Impairment (CrCl 10-30 mL/min)

• Treatment: 75 mg once daily for 5 days (reduce frequency from twice daily to once daily) 1, 2, 3
• Prophylaxis: Two acceptable options exist:
  • 30 mg once daily for 10 days after exposure, OR 1, 2, 3
  • 75 mg every other day for 10 days (total of 5 doses) 1, 2, 3

Severe Renal Impairment (CrCl <10 mL/min or Hemodialysis)

• Treatment: 30 mg per hemodialysis cycle 3, 4
• Prophylaxis: 30 mg every alternate hemodialysis cycle 3, 4
• The FDA label confirms that exposure in ESRD patients on hemodialysis receiving 30 mg per HD cycle achieves comparable drug levels to patients with normal renal function on standard dosing. 4

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• Treatment: 30 mg as a single dose achieves similar Day 5 concentrations (147 ng/mL) as standard twice-daily dosing in patients with normal renal function (predicted 160 ng/mL). 4
• Prophylaxis: 30 mg once weekly produces comparable trough levels (63 ng/mL) to standard once-daily prophylaxis in normal renal function (40 ng/mL). 4

Pediatric Renal Dosing Adjustments

• For children with CrCl 10-30 mL/min, reduce the weight-based dose frequency from twice daily to once daily for treatment. 2
• For pediatric prophylaxis with CrCl 10-30 mL/min, give half the standard once-daily dose once daily, or give the full once-daily dose every other day for 10 days (5 total doses). 2

Pharmacokinetic Rationale

• Oseltamivir carboxylate (the active metabolite) is eliminated >99% by renal excretion, with renal clearance (18.8 L/h) exceeding glomerular filtration rate (7.5 L/h), indicating tubular secretion via organic anion transporters. 4, 5
• Exposure to oseltamivir carboxylate is inversely proportional to declining renal function - the FDA label demonstrates that patients with severe renal impairment (CrCl 10-30 mL/min) receiving 30 mg once daily achieve AUC values (12,008 ng·h/mL) comparable to those with normal function on standard dosing (11,224 ng·h/mL). 4

Administration Considerations

• Oseltamivir can be taken without regard to meals, but administration with food may reduce gastrointestinal side effects (nausea, vomiting occur in ~10% of patients). 1, 2, 3
• Available formulations include 30 mg, 45 mg, and 75 mg capsules, plus oral suspension (6 mg/mL when reconstituted). 1, 2

Common Pitfalls to Avoid

• Do not confuse GFR with creatinine clearance - the 30 mL/min threshold specifically refers to creatinine clearance. 2, 3
• Do not delay the first dose - current guidelines that recommend immediate dose reduction may result in subtherapeutic concentrations during the critical first 24 hours of infection, particularly in patients with mild-moderate renal impairment or large body mass. 6
• Calculate creatinine clearance using ideal (lean) body weight at extremes of body mass to avoid under- or overestimating renal function. 7