Oseltamivir

Oseltamivir is appropriate for the treatment of acute, uncomplicated influenza A or B illness in adults and pediatric patients, including neonates greater than 2 weeks of age[1]. Neonates less than 2 weeks of age may also receive oseltamivir for treatment of influenza, but safety and efficacy in this population have not been established[2]. Multiple national advisory bodies have endorsed the use of oseltamivir as soon as possible (ideally less than 48 hours after symptom onset) for patients hospitalized with influenza or with significant comorbidities making them at high risk for complications[3]. There is some evidence in hospitalized patients that oseltamivir can have efficacy up to 4 to 5 days after symptoms onset and hence, recommendations endorse ordering oseltamivir for hospitalized patients with severe or progressive influenza illness or those patients at high risk of developing complications, regardless of the time of symptom onset[4]. Individuals at high risk for complications include young children (less than two years of age), those in nursing homes, those 65 years of age or older, obese, pregnant, patients with pulmonary, liver, renal, or cardiovascular disease, malignancy, neurodevelopmental disorders, metabolic disorders, epilepsy, muscular dystrophy, and immunosuppression. Empiric treatment with oseltamivir can shorten the duration of illness and is thus recommended for healthy individuals with symptoms suggestive of influenza, even before confirmation testing if treatment can commence within 48 hours of symptoms. Oseltamivir is also useful for influenza prophylaxis within 48 hours of contact with an infected individual in adults and children greater than 1 year of age.

Recommendations endorsing oseltamivir as the drug of choice for treatment and prophylaxis of illness caused by avian influenza strains, including the highly pathogenic avian influenza A (H5N1), come from the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO). 

Oseltamivir is an antiviral neuraminidase inhibitor, with potent and selective competitive inhibition of the influenza virus neuraminidase, an enzyme necessary for viral replication. Oseltamivir phosphate is an inactive prodrug that exerts pharmacologic activity when hydrolyzed in vivo to the active form, oseltamivir carboxylate. This activated form interferes with the release of progeny influenza virus from infected host cells and thus halts the spread of infection to new host cells. Oseltamivir reduces the duration of shedding and the viral titer and can shorten the length of symptoms by 0.5 to 3 days.[5]

Dosing of oseltamivir phosphate is via the oral route, and it is not necessary to time administration with meals. It is available in capsule form of three different dosages (30, 45, and 75 mg) and as an oral powder for reconstitution to suspension for pediatric patients. Therapy should initiate as early as possible, and maximum benefit is derived when initiated within 48 hours of onset of illness. However, in severe illness or patients at risk of complications, treatment must be initiated even beyond the 48-hour window.

Seasonal Influenza A and B treatment (five-day oral course):

• Adults: 75 mg BID
• Infants 0 to 8 months: 3 mg/kg/dose BID
• Infants 9 to 11 months: 3.5 mg/kg/dose BID
• Children 1 to 12 yrs old:
  • Less than 15 kg: 30 mg BID
  • Greater than 15 kg to less than 23 kg: 45 mg BID
  • Greater than 23 kg to less than 40 kg: 60 mg BID
  • Over 40 kg: 75 mg PO BID

Patients with severe infections admitted to an intensive care unit or who are immunosuppressed may require oseltamivir treatment for a prolonged indeterminate duration (more than 5 days).

Treatment dosing adjustments for creatinine clearance:

• CrCl 30 to 60 ml/min: 30 mg BID
• CrCl less than 30 ml/min: 30 mg daily
• Hemodialysis patients: 30 mg after dialysis x 5 days (assumes 3 HD sessions)

Seasonal Influenza A and B Prophylaxis (seven to 10-day oral course)[6]:

• Adults: 75 mg daily
• Infants 0 to 8 months: 3 mg/kg/dose daily (not indicated for under 3 months unless clinically critical)
• Infants 9-11 months: 3 mg/kg/dose daily
• Children 1-12 yrs old:
  • Less than 15 kg: 30 mg daily
  • Greater than 15 kg to less than 23 kg: 45mg daily
  • Greater than 23 kg to less than 40 kg: 60mg daily
  • Over 40 kg: 75 mg daily

While recommendations for oseltamivir include the treatment of avian influenza infections, the optimum dosage and duration of treatment are unknown for these infections.[7]

Oseltamivir is generally well tolerated.[8] Most common side effects are nausea (up to 10%), vomiting (2% to 15%), abdominal pain, diarrhea, headache, insomnia, and vertigo. Other side effects occurring less than 1% of the time include conjunctivitis, epistaxis, allergy, arrhythmia, GI bleeding, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, confusion, hepatitis, seizures, and neuropsychiatric events.[5][9] Vomiting is the most frequently reported side effect in children (16% of children aged 1 to 12 years).

Known allergies or hypersensitivities to oseltamivir or any component of the drug is a contraindication. It is pregnancy class C. Commercially available oral suspension of oseltamivir contains sorbitol and hence, should be used cautiously in patients with hereditary fructose intolerance. Oseltamivir should not be used in patients with influenza illnesses that are due to strains confirmed as resistant to oseltamivir. It should not be used for diseases that are caused by organisms other than influenza viruses.