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

From the Guidelines

Tamiflu (Oseltamivir) dosing adjustment for patients with impaired renal function is as follows:

• For treatment of patients with creatinine clearance 10–30 mL/min: 75 mg, once daily, for 5 d.
• For chemoprophylaxis of patients with creatinine clearance 10–30 mL/min: 30 mg, once daily, for 10 d after exposure or 75 mg, once every other day, for 10 d after exposure (5 doses) 1.

Key Points

• The dose should be adjusted on the basis of creatinine clearance in patients with renal insufficiency.
• Oseltamivir is available as Tamiflu in 30-, 45-, and 75-mg capsules and as a powder for oral suspension that is reconstituted to provide a final concentration of 6 mg/mL.
• If the commercially manufactured oral suspension is not available, a suspension can be compounded by retail pharmacies (final concentration also 6 mg/mL) on the basis of instructions contained in the package label.
• The CDC recommends adjusting the dose of oseltamivir in patients with renal insufficiency, and the FDA has approved oseltamivir for children as young as 2 weeks of age 1.

Dosage Administration

• Oseltamivir is administered orally without regard to meals, although administration with meals may improve gastrointestinal tolerability.
• For the 6-mg/mL suspension, a 30-mg dose is given with 5 mL of oral suspension, a 45-mg dose is given with 7.5 mL of oral suspension, a 60-mg dose is given with 10 mL of oral suspension, and a 75-mg dose is given with 12.5 mL of oral suspension.

Important Considerations

• Clinical judgment is an important factor in treatment decisions for patients who present with influenza-like illness.
• Antiviral treatment should be started as soon as possible after illness onset and should not be delayed while waiting for a definitive influenza test result, because early therapy provides the best outcomes.
• Influenza diagnostic tests vary by method, availability, processing time, sensitivity, and cost, which should be considered in making the treatment decisions.

From the FDA Drug Label

Adjust the oseltamivir phosphate for oral suspension dosage in patients with moderate or severe renal impairment [see Dosage and Administration (2.4)]. Oseltamivir phosphate for oral suspension is not recommended for patients with end-stage renal disease not undergoing dialysis [see Dosage and Administration (2.4)and Use in Specific Populations (8.6)]. Table 7 Simulated Median Treatment Exposure Metrics of Oseltamivir Carboxylate in Patients with Normal Renal Function, with Renal Impairment and ESRD Patients on Hemodialysis Renal Function/ImpairmentNormal Creatinine Clearance 90-140 mL/min (n=57) Mild Creatinine Clearance 60-90 mL/min (n=45) Moderate Creatinine Clearance 30-60 mL/min (n=13) Severe Creatinine Clearance 10-30 mL/min (n=11) ESRD Creatinine Clearance <10 mL/min on Hemodialysis (n=24)

• AUC normalized to 48 hours Recommended Treatment Regimens PK exposure parameter75 mg twice daily75 mg twice daily30 mg twice daily30 mg once daily30 mg every HD cycle

The dosing adjustment for Tamiflu (Oseltamivir) in patients with impaired renal function is as follows:

• Mild renal impairment (CrCl 60-90 mL/min): No adjustment needed, 75 mg twice daily.
• Moderate renal impairment (CrCl 30-60 mL/min): 30 mg twice daily.
• Severe renal impairment (CrCl 10-30 mL/min): 30 mg once daily.
• ESRD (CrCl < 10 mL/min) on hemodialysis: 30 mg every HD cycle. Note: These adjustments are based on the simulated median treatment exposure metrics of oseltamivir carboxylate in patients with normal renal function, with renal impairment, and ESRD patients on hemodialysis 2.

From the Research

Dosing Adjustments for Tamiflu (Oseltamivir) in Patients with Impaired Renal Function

• The dosing adjustment for Tamiflu (Oseltamivir) in patients with impaired renal function is based on the degree of renal impairment 3, 4, 5.
• For patients with normal renal function or mild renal impairment, the recommended dose is 75 mg twice daily 3, 5.
• For patients with moderate renal impairment, the recommended dose is 30 mg twice daily 3, 5.
• For patients with severe renal impairment, the recommended dose is 30 mg once daily 3, 5.
• In patients with end-stage renal disease (ESRD) undergoing haemodialysis or continuous ambulatory peritoneal dialysis, a dose of 30 mg once weekly or after alternate haemodialysis sessions is recommended 4.
• Current dosing recommendations may not provide adequate therapeutic concentrations in patients with mild to moderate renal impairment and/or large body mass, and therapeutic drug monitoring may be necessary to optimize dosing 6.

Pharmacokinetics of Oseltamivir in Patients with Renal Impairment

• Oseltamivir is renally cleared, and its pharmacokinetics are affected by renal impairment 3, 7, 5.
• The clearance of oseltamivir carboxylate, the active metabolite of oseltamivir, is reduced in patients with renal impairment, resulting in increased exposure 3, 7, 5.
• The volume of distribution of oseltamivir carboxylate does not increase with increasing body weight, and the rate of elimination is modestly correlated with creatinine clearance 7.