What is the appropriate oseltamivir dosing for a patient with an estimated glomerular filtration rate of 27 mL/min (severe renal impairment), for treatment and prophylaxis?

Oseltamivir Dosing for eGFR 27 mL/min

For a patient with an eGFR of 27 mL/min (severe renal impairment, CrCl 10–30 mL/min), reduce oseltamivir to 75 mg once daily for treatment (5 days) and 75 mg every other day for prophylaxis (10 days total, 5 doses). 1, 2, 3

Dosing Algorithm for Severe Renal Impairment (CrCl 10–30 mL/min)

Treatment Regimen

• Dose: 75 mg orally once daily (not twice daily) for 5 days 1, 2, 3, 4
• Timing: Initiate within 48 hours of symptom onset for maximum benefit 5
• Administration: Take with food to reduce nausea and vomiting, which occur in ~10–15% of patients 5

Prophylaxis Regimen

• Dose: 75 mg orally every other day for 10 days (total of 5 doses) 1, 2, 3
• Alternative: 30 mg once daily for 10 days is also acceptable 3, 5
• Timing: Begin within 48 hours of exposure to an infected individual 5

Rationale and Evidence Strength

The dose reduction threshold is CrCl <30 mL/min, not age or other factors. 1, 2, 3 Your patient's eGFR of 27 mL/min falls squarely into the "severe renal impairment" category requiring mandatory dose adjustment. 2, 3

Why the reduction is necessary:

• Oseltamivir carboxylate (the active metabolite) is eliminated >99% by renal excretion via glomerular filtration and tubular secretion. 4, 6, 7
• Serum concentrations of oseltamivir carboxylate increase inversely with declining renal function. 1, 4
• Without dose reduction, patients with CrCl 10–30 mL/min achieve 2–3 times higher drug exposure than those with normal renal function, risking toxicity. 4, 8

The evidence is uniform across all major guidelines:

• The Advisory Committee on Immunization Practices (ACIP) consistently recommends 75 mg once daily for treatment and 75 mg every other day for prophylaxis in patients with CrCl 10–30 mL/min. 1
• The FDA label endorses identical dosing based on population pharmacokinetic modeling showing that these regimens produce oseltamivir carboxylate exposures comparable to standard dosing in patients with normal renal function. 4, 8
• Recent pharmacokinetic studies confirm that 30 mg twice daily (an alternative treatment regimen) and 30 mg once daily (an alternative prophylaxis regimen) also achieve therapeutic concentrations without excessive accumulation. 2, 3, 8

Critical Pitfalls to Avoid

Do NOT use standard dosing (75 mg twice daily)

• Standard dosing in severe renal impairment produces median trough concentrations of 577 ng/mL versus 145 ng/mL in normal renal function—a nearly 4-fold increase that raises toxicity risk. 4

Do NOT wait for dialysis dosing

• Your patient has CrCl 27 mL/min, not end-stage renal disease requiring hemodialysis. 1
• Hemodialysis dosing (30 mg per dialysis cycle) applies only to CrCl <10 mL/min or patients on chronic dialysis. 2, 3, 9

Do NOT adjust dose based on age alone

• No dose reduction is recommended based on age, even in patients >65 years, as long as renal function is preserved. 1, 5
• The key determinant is renal function, not chronological age. 5

Do NOT round or estimate creatinine clearance casually

• Use the Cockcroft-Gault equation or measured CrCl to determine the exact renal function category. 2, 3
• eGFR and CrCl are not interchangeable; CrCl is the standard for oseltamivir dosing adjustments. 2, 3

Alternative: Zanamivir for Renal Impairment

If oseltamivir dosing is uncertain or the patient has additional risk factors, consider zanamivir (inhaled). 1, 2

• No dose adjustment required for any degree of renal impairment, including severe impairment or end-stage renal disease. 1, 2
• Dosing: 10 mg (two inhalations) twice daily for treatment or once daily for prophylaxis, regardless of renal function. 2
• Rationale: Zanamivir is administered by oral inhalation, resulting in minimal systemic absorption and negligible renal clearance. 1
• Caveat: Zanamivir requires proper inhaler technique and is contraindicated in patients with underlying airway disease (asthma, COPD) due to risk of bronchospasm. 2

Monitoring and Safety Considerations

Gastrointestinal tolerability

• Nausea and vomiting are the most common adverse effects (~10–15% incidence). 5
• Administration with food significantly reduces GI symptoms without affecting drug absorption. 5, 4
• Only ~1% of patients discontinue oseltamivir due to GI side effects. 5

Renal function monitoring

• Patients with any degree of renal insufficiency should be monitored for adverse effects. 1
• If toxicity develops (e.g., neuropsychiatric symptoms, severe GI distress), further dose reduction or discontinuation may be necessary. 1

Therapeutic drug monitoring (TDM)

• TDM is not routinely recommended but may be valuable in patients with unpredictable pharmacokinetics (e.g., fluctuating renal function, obesity, critical illness). 10, 7
• Target trough concentrations of oseltamivir carboxylate are ~160–220 ng/mL for treatment and ~40–70 ng/mL for prophylaxis. 4, 9

Summary of Dosing for eGFR 27 mL/min

Indication	Dose	Frequency	Duration
Treatment	75 mg PO	Once daily	5 days
Prophylaxis	75 mg PO	Every other day	10 days (5 doses)
Alternative prophylaxis	30 mg PO	Once daily	10 days

1, 2, 3, 4