Treatment of “Classic” Human Influenza 177

Special Situations

Children

Oseltamivir: children 1 to 12 years of age clear the active metabolite oseltamivir carboxylate at a faster rate than older children and adults, resulting in lower exposure. Increasing the dose to 2 mg/kg twice daily results in drug exposures comparable to the standard 1 mg/kg twice daily dose used in adults (Oo 2001). Infants as young as 1 year old can metabolise and excrete oseltamivir efficiently (Oo 2003), but in younger children, use of oseltamivir is contraindicated (FDA 2005).

Zanamivir: In the EU, zanamivir is approved for use in children aged 12 years or older (US: 7 years).

Amantadine, rimantadine: Given the relatively low efficacy and the high risk of developing gastrointestinal and CNS adverse effects, the authors do not recommend administration of amantadine or rimantadine to children.

Impaired Renal Function

Oseltamivir: the terminal plasma elimination half-life is 1.8 h in healthy adults. In patients with renal impairment, metabolite clearance decreases linearly with creatinine clearance, and averages 23 h after oral administration in individuals with a creatinine clearance < 30 ml/min (Doucette 2001). A dosage reduction to 75 mg once daily is recommended for patients with a creatinine clearance < 30 ml/min (1.8 l/h) (He 1999); in prophylaxis, a dosage of 75 mg every other day is recommended. No treatment or prophylaxis dosing recommendations are available for patients on renal dialysis treatment.

Zanamivir: the manufacturer declares that there is no need for dose adjustment during a 5-day course of treatment for patients with either mild-to-moderate or severe impairment in renal function (Relenza).

Rimantadine: renal insufficiency results in increased plasma concentrations of rimantadine metabolites. Haemodialysis does not remove rimantadine. A reduction to 100 mg/day is recommended in patients with a creatinine clearance < 10 ml/min. Supplemental doses on dialysis days are not required (Capparelli 1988). In patients with less severe renal insufficiency, and in older persons, rimantidine should be monitored for adverse effects.

Amantadine: a dose reduction is recommended for individuals > 60 years and with a creatinine clearance < 40 ml/min. Guidelines for amantadine dosage on the basis of creatinine clearance are located in the package insert. Patients should be observed carefully for adverse reactions. In these cases, consider further dose reduction or discontinuation of the drug. Amantadine is not removed by haemodialysis.

Impaired Liver Function

Oseltamivir: the metabolism of oseltamivir is not compromised in patients with moderate hepatic impairment, and dose adjustment is not required in these patients (Snell 2005).

Zanamivir: has not been studied in persons with hepatic dysfunction.

Rimantadine: for persons with severe hepatic dysfunction, a dose reduction of rimantadine is recommended.