Oseltamivir

Oseltamivir is an oral prodrug of a neuraminidase inhibitor active against influenza A and B. It shortens illness by about a day when given within 48 hours of onset and is used mainly for people at risk of complications and for hospitalised patients, even when started later. It is also used for post-exposure prophylaxis. Nausea and vomiting are common, and neuropsychiatric events are uncommon but reported, particularly in children.

Class. Neuraminidase inhibitor antiviral.

Mechanism. The active carboxylate blocks viral neuraminidase, preventing release of virions from infected cells. The H275Y mutation causes resistance in influenza A(H1N1).

Pharmacokinetics. Oral bioavailability about 75% as the active metabolite, rapid hepatic esterase conversion, half life 6 to 10 hours, renal excretion by filtration and tubular secretion.

Influenza treatment (adults and children 13 years and over). 75 mg orally twice daily for 5 days; start within 48 hours if possible, but also treat severe or hospitalised illness started later. In critical illness or immunosuppression, courses of 5 to 10 days; higher doses have no proven benefit.

Post-exposure prophylaxis. 75 mg once daily for 7 to 10 days after contact; up to 6 weeks (and for the duration of an outbreak) in specific settings, started within 48 hours of exposure.

Children treatment doses (twice daily for 5 days). - 15 kg or less: 30 mg. Over 15 to 23 kg: 45 mg. Over 23 to 40 kg: 60 mg. Over 40 kg: 75 mg. - Infants under 1 year: 3 mg/kg for each dose; premature infants are dosed by postmenstrual age.

Dose adjustment for kidney function (adults).

• Treatment: CrCl 31 to 60 mL/min 30 mg twice daily; 11 to 30: 30 mg once daily; 10 or less: single 30 mg dose or 30 mg after dialysis, by specialist advice.
• Prophylaxis: CrCl 31 to 60: 30 mg once daily; 11 to 30: 30 mg every other day.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 150 mg daily.

Main alternatives. Inhaled zanamivir, baloxavir marboxil, or intravenous peramivir where available.

Contraindications. Hypersensitivity to oseltamivir.

Serious adverse effects. Anaphylaxis, severe skin reactions (Stevens-Johnson syndrome), and neuropsychiatric events (delirium, self-injury) in children and adolescents.

Common adverse effects. Nausea, vomiting (reduced by taking with food), abdominal pain and headache.

Interactions. Live attenuated intranasal influenza vaccine should not be given within 2 weeks after or 48 hours before oseltamivir; probenecid raises levels. Few other interactions.

Common prescribing errors. Waiting for a test result before treating high-risk patients, wrong paediatric weight band, and not reducing the dose in kidney failure.

Special groups.

• Pregnancy: treat promptly; benefit outweighs risk, and the drug is used in any trimester.
• Breastfeeding: compatible; low milk levels.
• Children: weight-based; monitor for behavioural change.
• Older adults: usual dose; adjust for kidney function.
• Kidney impairment: treatment 30 mg twice daily at CrCl 31 to 60 mL/min and 30 mg once daily at CrCl 11 to 30.
• Liver impairment: no adjustment.

Formulations. Capsules 30 mg, 45 mg and 75 mg; powder for oral suspension 6 mg/mL.

Administration. With food to reduce nausea. For those unable to swallow, open the capsule into sweet liquid.

Baseline. Creatinine for dosing; confirm influenza by test where available, but do not delay treatment in high-risk or severe cases.

Monitoring. Clinical response at 48 hours; neuropsychiatric symptoms in children; creatinine in critical illness.

Stopping thresholds. Stop for anaphylaxis, severe skin reaction or marked neuropsychiatric symptoms.

Referral and escalation. Admission for respiratory distress, hypoxia, pneumonia or deterioration; specialist review for immunocompromised patients and suspected resistance.