oseltamivir

Brand: Tamiflu

Prototype Drug
Drug Class: antiviral
Drug Family: antiviral
Subclass: neuraminidase inhibitor
Organ Systems: infectious-disease

Mechanism of Action

Prodrug converted by hepatic esterases to oseltamivir carboxylate, which competitively inhibits influenza A and B neuraminidase; neuraminidase is required for viral budding and release from infected cells, limiting viral spread.

influenza neuraminidase

Indications

  • influenza A and B treatment (within 48 hours of symptom onset)
  • influenza prophylaxis (post-exposure and seasonal)
  • treatment of serious influenza in hospitalized patients (regardless of symptom duration)
  • H5N1 avian influenza (treatment and prophylaxis)

Contraindications

  • known hypersensitivity to oseltamivir

Adverse Effects

Common

  • nausea
  • vomiting (take with food to minimize)
  • headache
  • diarrhea

Serious

  • neuropsychiatric events (confusion, hallucinations, self-injury — reported mainly in pediatric patients in Japan; causality uncertain)
  • bronchospasm (rare)
  • serious skin reactions

Pharmacokinetics (ADME)

Absorption ~75% oral bioavailability as oseltamivir carboxylate; food does not affect bioavailability
Distribution Oseltamivir carboxylate: protein binding 3%; widely distributed
Metabolism Prodrug hydrolyzed by hepatic esterases (primarily CES1) to active carboxylate
Excretion Renal; dose adjustment for CrCl <30 mL/min
Half-life 6–10 hours (carboxylate)
Onset 1–2 hours
Peak 3–4 hours
Duration 12 hours (q12h dosing x5 days for treatment)
Protein Binding 3%
Vd ~23 L

Drug Interactions

Drug / Agent Mechanism Severity
probenecid reduces renal tubular secretion of oseltamivir carboxylate; doubles levels minor
influenza live attenuated vaccine (LAIV) oseltamivir may reduce LAIV efficacy — separate by 48 hours before and 2 weeks after LAIV moderate

Nursing Considerations

  1. Administer within 48 hours of symptom onset for maximum benefit; treatment beyond 48 hours may still be beneficial in severe illness, hospitalized patients, or immunocompromised hosts
  2. Take with food to reduce GI side effects; suspension can be prepared from capsules if needed for patients who cannot swallow capsules
  3. Renal dose adjustment: for CrCl 10–30 mL/min, reduce to 75 mg once daily (treatment) or 30 mg once daily (prophylaxis); for CrCl <10 or ESRD on dialysis, specific dosing protocols apply
  4. For post-exposure prophylaxis: 75 mg once daily x10 days; for seasonal prophylaxis: 75 mg once daily for up to 6 weeks during outbreak period

Clinical Pearls

  • Oseltamivir reduces duration of influenza by approximately 1 day and reduces risk of complications (pneumonia, hospitalization) — benefits are most pronounced in high-risk patients (elderly, immunocompromised, pregnant) even when started late
  • Oseltamivir resistance in influenza A (H275Y mutation in neuraminidase) has been documented in seasonal H1N1 strains and in immunocompromised patients on prolonged therapy — peramivir IV or inhaled zanamivir may be alternatives

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required