Introduction
Oseltamivir phosphate is an antiviral medication belonging to the neuraminidase inhibitor class. Marketed under the brand name Tamiflu®, it is primarily indicated for the treatment and prophylaxis of influenza A and B virus infections. Since its FDA approval in 1999, oseltamivir has become a cornerstone in the management of seasonal influenza outbreaks and pandemic preparedness.
Mechanism of Action
Oseltamivir is a prodrug that undergoes hepatic hydrolysis to its active metabolite, oseltamivir carboxylate. This active form selectively inhibits influenza neuraminidase enzymes, which are essential for viral replication. Neuraminidase facilitates the release of newly formed virions from infected host cells and prevents viral aggregation. By inhibiting this enzyme, oseltamivir effectively prevents viral spread within the respiratory tract, reducing both the duration and severity of influenza symptoms.
Indications
- Treatment of uncomplicated acute influenza illness in patients ≥2 weeks old who have been symptomatic for ≤48 hours
- Post-exposure prophylaxis of influenza in patients ≥1 year old
- Seasonal prophylaxis of influenza in patients ≥1 year old
Dosage and Administration
Treatment dosing:- Adults and adolescents (≥13 years): 75 mg twice daily for 5 days
- Children (1-12 years): Weight-based dosing:
- ≤15 kg: 30 mg twice daily - >15-23 kg: 45 mg twice daily - >23-40 kg: 60 mg twice daily - >40 kg: 75 mg twice daily
- Infants (2 weeks to <1 year): 3 mg/kg twice daily
- Adults and adolescents (≥13 years): 75 mg once daily for at least 10 days after exposure
- Children (1-12 years): Weight-based once daily dosing following same weight categories as treatment
- CrCl 30-60 mL/min: Reduce treatment dose to 30 mg twice daily; prophylaxis to 30 mg once daily
- CrCl 10-30 mL/min: Reduce treatment dose to 30 mg once daily; prophylaxis to 30 mg every other day
- ESRD on hemodialysis: 30 mg after each dialysis session
Pharmacokinetics
Absorption: Oseltamivir phosphate is readily absorbed from the GI tract and extensively converted to oseltamivir carboxylate by hepatic esterases. Bioavailability of the active metabolite is approximately 80%. Food does not significantly affect absorption. Distribution: The active metabolite distributes throughout the body, including respiratory secretions. Protein binding is minimal (3%). Metabolism: Hepatic esterases convert the prodrug to the active carboxylate metabolite. Elimination: Primarily renal excretion of the active metabolite (≥99%). Half-life is 6-10 hours for the active metabolite.Contraindications
- Known hypersensitivity to oseltamivir or any component of the formulation
- Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (due to excipients)
Warnings and Precautions
- Neuropsychiatric events: There have been postmarketing reports of delirium and abnormal behavior leading to injury; monitor patients closely
- Bacterial infections: Oseltamivir is not effective against bacterial infections; superinfections may occur
- Renal impairment: Dose adjustment required in patients with CrCl <60 mL/min
- Pregnancy: Use only if potential benefit justifies potential risk (Pregnancy Category C)
- Breastfeeding: Oseltamivir carboxylate is excreted in breast milk; use with caution
Drug Interactions
- Live attenuated influenza vaccine: Oseltamivir may reduce vaccine efficacy; separate administration by at least 48 hours
- Probeneci d: May decrease clearance of oseltamivir carboxylate, increasing systemic exposure
- No clinically significant interactions with CYP450 enzymes
Adverse Effects
Common (≥1%):- Nausea (10%)
- Vomiting (8%)
- Headache (2%)
- Diarrhea (5%)
- Abdominal pain (2%)
- Anaphylaxis and serious skin reactions (Stevens-Johnson syndrome)
- Hepatotoxicity
- Neuropsychiatric events (seizures, confusion, abnormal behavior)
- Hemorrhagic colitis
Monitoring Parameters
- Clinical symptoms of influenza
- Hydration status (especially in children with vomiting)
- Renal function in patients with pre-existing renal impairment
- Neuropsychiatric symptoms (particularly in children and adolescents)
- Signs of secondary bacterial infections
Patient Education
- Begin treatment within 48 hours of symptom onset for maximum benefit
- Complete the full 5-day course even if symptoms improve
- Take with food to reduce gastrointestinal upset
- Report any unusual behavior, confusion, or psychiatric symptoms immediately
- Oseltamivir is not a substitute for annual influenza vaccination
- Store at room temperature (15-30°C/59-86°F)
References
1. FDA Prescribing Information: Tamiflu (oseltamivir phosphate) capsules and oral suspension. 2021 2. Infectious Diseases Society of America. Clinical Practice Guidelines by the IDSA: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clinical Infectious Diseases. 2019;68(6):895-902 3. Whitley RJ, Hayden FG, Reisinger KS, et al. Oral oseltamivir treatment of influenza in children. Pediatric Infectious Disease Journal. 2001;20(2):127-133 4. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in adults and children. Cochrane Database of Systematic Reviews. 2014;(4):CD008965 5. Kimberlin DW, Brady MT, Jackson MA, Long SS. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. American Academy of Pediatrics; 2018