How should oseltamivir (Tamiflu) be dosed in adults with impaired renal function (creatinine clearance 10–30 mL/min or <10 mL/min) for treatment and prophylaxis?

Oseltamivir Dosing in Renal Impairment

For adults with creatinine clearance 10–30 mL/min, reduce oseltamivir to 30 mg once daily for treatment (5 days) and 30 mg every other day for prophylaxis; for CrCl <10 mL/min or hemodialysis patients, use 30 mg after each dialysis cycle for treatment and after every alternate cycle for prophylaxis. 1

Dosing Algorithm by Renal Function

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

Treatment regimen:

• 30 mg orally once daily for 5 days 1, 2
• This represents a 75% reduction from the standard 75 mg twice-daily dose 3
• The FDA label explicitly recommends this regimen to prevent drug accumulation 1

Prophylaxis regimen:

• 30 mg orally every other day for the recommended prophylaxis duration (typically 10 days) 1, 3
• Alternative: 30 mg once daily may be used, though every-other-day dosing is preferred per FDA guidance 1

Severe Renal Impairment (CrCl <10 mL/min)

For patients on hemodialysis:

• Treatment: 30 mg immediately, then 30 mg after each hemodialysis session (not to exceed 5 days total) 1, 4
• Prophylaxis: 30 mg immediately, then 30 mg after every alternate hemodialysis cycle for the recommended duration 1, 4

For patients on continuous ambulatory peritoneal dialysis (CAPD):

• Treatment: Single 30 mg dose immediately 1
• Prophylaxis: 30 mg immediately, then 30 mg once weekly for the recommended duration 1

Critical caveat: Oseltamivir is not recommended for patients with end-stage renal disease who are not undergoing dialysis 1

Pharmacokinetic Rationale

• Oseltamivir carboxylate (the active metabolite) is eliminated >99% by renal excretion via tubular secretion 5
• In patients with CrCl 10–30 mL/min, drug exposure increases 2–3 fold compared to normal renal function without dose adjustment 4, 5
• Metabolite clearance decreases linearly with declining creatinine clearance 5, 3
• The threshold for mandatory dose reduction is CrCl <30 mL/min, not age or other factors 4, 3

Common Pitfalls to Avoid

Do not use 75 mg once daily for CrCl 10–30 mL/min:

• Older guidelines (2004–2010) recommended 75 mg once daily for this population 3
• Current FDA labeling (2024) specifies 30 mg once daily based on updated pharmacokinetic modeling 1, 2
• The 2015 pharmacokinetic study that informed the revised FDA label demonstrated that 30 mg regimens provide OC exposures similar to or above those achieved with 75 mg twice daily in patients with normal renal function 2

Do not delay the first dose:

• A 2021 review highlighted that current dose-reduction strategies focus on steady-state concentrations but overlook the critical importance of achieving therapeutic levels early in infection 6
• For patients with mild-to-moderate impairment (CrCl 30–60 mL/min), consider giving the first dose at 75 mg, then reducing subsequent doses to 30 mg twice daily to ensure rapid therapeutic concentrations 6

Do not adjust dose based on age alone:

• Elderly patients (>65 years) do not require dose reduction unless renal function is impaired 3, 4
• However, calculate creatinine clearance in all elderly patients, as renal function declines with age 7

Alternative: Zanamivir for Renal Impairment

Zanamivir (inhaled) requires no dose adjustment for any degree of renal impairment, including end-stage renal disease 4, 8

Dosing:

• Treatment: 10 mg (two 5-mg inhalations) twice daily for 5 days 8
• Prophylaxis: 10 mg once daily for 10 days 8

Rationale:

• Only 4–17% of inhaled zanamivir is absorbed systemically; the remainder is deposited in the oropharynx and excreted in feces 8
• Minimal renal clearance eliminates the need for dose adjustment 3, 8

Contraindication:

• Do not use zanamivir in patients with asthma or COPD due to risk of life-threatening bronchospasm 8

Monitoring Recommendations

• Assess renal function (calculate creatinine clearance, not just serum creatinine) before initiating oseltamivir 4, 7
• Monitor for toxicity in all patients with any degree of renal insufficiency, including neuropsychiatric symptoms (confusion, abnormal behavior) and severe gastrointestinal distress 7, 3
• Consider therapeutic drug monitoring in critically ill patients or those with fluctuating renal function to optimize dosing 6

Summary Table

Renal Function	Treatment Dose	Frequency	Duration	Prophylaxis Dose	Frequency
CrCl 10–30 mL/min	30 mg	Once daily	5 days	30 mg	Every other day
CrCl <10 mL/min (HD)	30 mg	After each HD	5 days	30 mg	After alternate HD
CrCl <10 mL/min (CAPD)	30 mg	Single dose	—	30 mg	Once weekly

All recommendations based on current FDA labeling (2024) 1 and CDC/ACIP guidelines 3, 4