What is the dose of oseltamivir (Tamiflu) for a patient with impaired renal function?

Oseltamivir Dosing in Renal Impairment

For patients with creatinine clearance 10-30 mL/min, reduce oseltamivir to 75 mg once daily for treatment (instead of twice daily) and 75 mg every other day for prophylaxis; for patients with CrCl <10 mL/min on hemodialysis, administer 30 mg after each dialysis session for treatment and 30 mg after every other dialysis session for prophylaxis. 1, 2

Critical Threshold for Dose Adjustment

• The key threshold requiring dose reduction is CrCl <30 mL/min, not higher values. 1
• No dose adjustment is required based on age alone, even in elderly patients—renal function is the sole determining factor. 3, 1
• Oseltamivir carboxylate (the active metabolite) is eliminated >99% by renal excretion, with clearance inversely proportional to declining renal function. 4, 5

Standard Dosing (CrCl ≥30 mL/min)

• Treatment: 75 mg orally twice daily for 5 days 1, 2
• Prophylaxis: 75 mg orally once daily for 10 days post-exposure or up to 6 weeks during community outbreak 1, 2

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

• Treatment: 75 mg once daily for 5 days (50% dose reduction from standard twice-daily regimen) 3, 1, 2
• Prophylaxis: 75 mg every other day for 10 days (5 total doses) OR 30 mg once daily for 10 days 3, 1, 2
• These regimens produce oseltamivir carboxylate exposures similar to or above those achieved with standard dosing in patients with normal renal function. 6

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

• Treatment: 30 mg administered after each hemodialysis session 1, 7
• Prophylaxis: 30 mg after every other hemodialysis session 1, 7
• Oseltamivir carboxylate clearance during hemodialysis (7.43 L/min) is approximately 40-fold faster than between dialysis sessions (0.19 L/min). 7
• If influenza is diagnosed between dialysis sessions, administer a single 30 mg dose immediately without waiting for the next session—this raises concentrations quickly without safety concerns. 7

Severe Renal Impairment NOT on Dialysis

• No specific dosing recommendations are available for patients with CrCl <10 mL/min who are not undergoing dialysis. 3, 4
• Consider alternative therapy with zanamivir (inhaled), which requires no dose adjustment regardless of renal function. 1

Continuous Ambulatory Peritoneal Dialysis (CAPD)

• 30 mg once weekly produces oseltamivir carboxylate concentrations comparable to standard prophylaxis dosing in patients with normal renal function. 4
• Peak concentrations are approximately 3-fold higher than in patients with normal renal function receiving 75 mg twice daily, but remain within safe limits. 4

Alternative: Zanamivir for Any Degree of Renal Impairment

• Zanamivir (10 mg inhaled twice daily for treatment, once daily for prophylaxis) requires no dose adjustment in any degree of renal impairment, including end-stage renal disease. 3, 1
• Only 4-17% of inhaled zanamivir is systemically absorbed; the remainder is deposited in the oropharynx and excreted in feces. 3
• This makes zanamivir a suitable alternative when oseltamivir dosing is uncertain or contraindicated. 1

Critical Timing Considerations

• Treatment must be initiated within 48 hours of symptom onset for maximum effectiveness, regardless of renal function. 2, 8
• The importance of achieving therapeutic concentrations early in infection is paramount—delayed attainment due to underdosing may reduce or negate efficacy. 9

Common Pitfalls to Avoid

• Do not reduce the initial loading dose in renal impairment—some evidence suggests the first dose should remain 75 mg to achieve therapeutic concentrations rapidly, with subsequent doses reduced according to renal function. 9
• Do not use CrCl thresholds other than 30 mL/min—dose reduction at higher CrCl values (e.g., 60 mL/min) is not supported by guidelines and may result in subtherapeutic exposure. 1
• Administer with food to reduce gastrointestinal side effects (nausea/vomiting occur in 10-15% of patients). 2, 8

Pharmacokinetic Rationale

• Oseltamivir carboxylate exposure increases proportionally as renal function declines—in patients with CrCl 10-30 mL/min, AUC is approximately 2-fold higher than in those with normal function when standard doses are used. 4, 6
• The recommended dose reductions maintain steady-state trough concentrations (C_min) above the median values achieved in patients with normal renal function receiving standard dosing. 4, 6
• Hemodialysis removes oseltamivir carboxylate efficiently, necessitating post-dialysis dosing to maintain therapeutic levels. 7