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

Tamiflu (Oseltamivir) Renal Dose Adjustment

For patients with creatinine clearance (CrCl) 10-30 mL/min, reduce the treatment dose to 75 mg once daily for 5 days and the prophylaxis dose to 75 mg every other day; for patients with CrCl <10 mL/min or on hemodialysis, use 30 mg per hemodialysis cycle for treatment and 30 mg every alternate hemodialysis cycle for prophylaxis. 1, 2

Critical Threshold for Dose Adjustment

• The key threshold for oseltamivir dose reduction is CrCl <30 mL/min, not 46 mL/min or other values. 1, 3
• No dose adjustment is required based on age alone, even in patients >65 years. 3

Standard Dosing (CrCl ≥30 mL/min)

• Treatment regimen: 75 mg orally twice daily for 5 days. 1, 4
• Prophylaxis regimen: 75 mg orally once daily for at least 10 days following exposure or up to 6 weeks during community outbreak. 1, 4
• These doses apply to all patients with CrCl ≥30 mL/min regardless of whether renal function is normal or mildly impaired. 3

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

• Treatment dose: 75 mg once daily for 5 days (reduced from twice daily). 1, 3, 5
  • Alternative treatment option: 30 mg twice daily, though 75 mg once daily is preferred as it provides more consistent exposure. 1, 5
• Prophylaxis dose: 75 mg every other day OR 30 mg once daily. 1, 3
  • The 75 mg every other day regimen provides 5 total doses over 10 days. 1

Severe Renal Impairment (CrCl <10 mL/min)

For Patients on Hemodialysis

• Treatment dose: 30 mg administered after each hemodialysis session. 1, 2, 6
  • If influenza is diagnosed between hemodialysis sessions, give a single 30 mg dose immediately (within 12 hours before next HD session) to achieve therapeutic levels quickly, then continue with 30 mg after each subsequent HD session. 6
• Prophylaxis dose: 30 mg after every alternate hemodialysis session. 1, 2, 6
• Hemodialysis significantly increases oseltamivir carboxylate clearance (7.43 L/min during HD vs 0.19 L/min between sessions), necessitating post-dialysis dosing. 6

For Patients NOT on Dialysis

• Oseltamivir is not recommended for end-stage renal disease patients not undergoing dialysis due to lack of dosing data and risk of drug accumulation. 4
• For continuous ambulatory peritoneal dialysis (CAPD) patients, 30 mg once weekly has been studied and produces comparable trough concentrations to standard prophylaxis dosing. 4

Pharmacokinetic Rationale

• Oseltamivir carboxylate (the active metabolite) is eliminated >99% by renal excretion via glomerular filtration and tubular secretion through the organic anion transporter pathway. 4, 7
• Exposure to oseltamivir carboxylate increases inversely with declining renal function—patients with CrCl 10-30 mL/min have approximately 10-fold higher exposure than those with normal renal function when given standard doses. 4, 5
• The half-life of oseltamivir carboxylate extends from 6-10 hours in normal renal function to significantly longer in renal impairment, increasing accumulation risk. 4, 7

Clinical Considerations and Pitfalls

• Administer with food to reduce gastrointestinal side effects (nausea and vomiting), though food does not significantly affect absorption. 1, 8, 4
• Do not confuse GFR with creatinine clearance—the 30 mL/min threshold refers to creatinine clearance, which should be calculated using the Cockcroft-Gault equation for dosing purposes. 1
• Initiate treatment within 48 hours of symptom onset for maximum benefit in immunocompetent patients, though immunocompromised patients may benefit from treatment initiated beyond this window. 2, 4
• Monitor for adverse effects in any patient with renal impairment, as even mild renal dysfunction can increase drug exposure. 3
• Recent evidence suggests current dosing recommendations may be suboptimal for patients with mild-to-moderate renal impairment and those with large body mass, as reduced doses delay achievement of therapeutic concentrations in the critical first 24 hours of infection. 9
  • Consider using a standard 75 mg first dose even in renal impairment to achieve rapid therapeutic levels, then reduce subsequent doses proportionally. 9
  • Therapeutic drug monitoring can optimize dosing when available. 9

Alternative: Zanamivir for Renal Impairment

• Zanamivir (inhaled) requires no dose adjustment in any degree of renal impairment, including end-stage renal disease, making it the simplest option for patients with severe renal dysfunction. 2, 3
• Only 4-17% of inhaled zanamivir is systemically absorbed, with minimal renal elimination burden. 2, 3
• Zanamivir dosing: 10 mg (two inhalations) twice daily for treatment or once daily for prophylaxis, regardless of renal function. 2