NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
Moushumi Sur ; Michael J. Lopez ; Preeti Patel ; Mari B. Baker .
Last Update: February 28, 2024 .
Oseltamivir is an antiviral medication used to manage acute, uncomplicated influenza A or B in adult and pediatric patients, including neonates older than 2 weeks. For neonates younger than 2 weeks, using oseltamivir to treat influenza is considered, although the safety and efficacy in this population remain unestablished. National advisory bodies advocate the initiation of oseltamivir within 48 hours of symptom onset, particularly for individuals hospitalized with influenza or possessing significant comorbidities placing them at heightened risk for complications. This activity explores oseltamivir's indications, mechanism of action, administration protocols, significant adverse effects, contraindications, monitoring strategies, and potential toxicity. The goal is to equip healthcare providers with the necessary knowledge to guide patient therapy effectively, ultimately optimizing outcomes in the combat against influenza and related viral infections.
Identify the indications for using oseltamivir. Evaluate the mechanism of action of oseltamivir. Assess the adverse drug reactions of oseltamivir.Implement effective collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from oseltamivir treatment.
Oseltamivir is appropriate for treating acute, uncomplicated influenza A or B illness in adults and pediatric patients, including neonates older than 2 weeks.[1] Neonates younger than 2 weeks may also receive oseltamivir for the treatment of influenza, but safety and efficacy in this population have not been established.[2]
FDA-Approved Indications
Oseltamivir has received approval from the FDA for treating and preventing both influenza A and B infections. They are indicated for managing acute, uncomplicated cases in individuals 2 weeks and older, provided symptoms have emerged within 48 hours. Additionally, oseltamivir is considered suitable for prophylactic use in patients 1 year and older.
The American Academy of Pediatrics guidelines recommend using oseltamivir to treat influenza in preterm infants, but it is not recommended for chemoprophylaxis in preterm infants. Consultation with a pediatric infectious disease physician is recommended in preterm infants younger than 28 weeks.[3] Empiric treatment with oseltamivir can shorten the duration of illness and is recommended for healthy individuals with symptoms suggestive of influenza, even before confirmation testing if treatment is initiated within 48 hours of symptoms. Multiple national advisory bodies have endorsed using oseltamivir as soon as possible (ideally less than 48 hours after symptom onset) for patients hospitalized with influenza or significant comorbidities, placing them at high risk for complications.[4]
There is evidence that oseltamivir can have efficacy in hospitalized patients up to 4 to 5 days after symptoms onset. Hence, recommendations endorse ordering oseltamivir for hospitalized patients with severe or progressive influenza or those at high risk of developing complications, regardless of symptom onset.[5] Individuals at increased risk for complications include children younger than 2, nursing home residents, adults who are obese or older than 65, pregnant women, and patients with pulmonary, liver, renal, or cardiovascular disease, malignancy, neurodevelopmental disorders, metabolic disorders, epilepsy, muscular dystrophy, and immunosuppression.
Off-Label Uses
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 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.[6]
Mechanism of Resistance: The mechanism of resistance of influenza viruses involves antigenic drift and shift in their surface glycoproteins. Antigenic drift is the process in which minor modifications occur in key viral epitopes through point mutations; antigenic shift results in a complete exchange of hemagglutinin (HA) or neuraminidase (NA) genes. Antigenic shift emerges mainly in influenza A viruses due to their vast animal reservoirs. Antigenic shift is a process frequently associated with the outbreak of pandemics.[7]
Pharmacokinetics
Absorption: Oseltamivir is an orally administrated prodrug. The oral bioavailability of oseltamivir is approximately 80%. Oral intake does not seem to impact the pharmacokinetics of oseltamivir significantly.
Distribution: The volume of distribution is approximately 23 to 26 liters. Oseltamivir is moderately bound to plasma proteins (42%), while oseltamivir carboxylate has poor plasma protein binding.
Metabolism: Hepatic carboxylesterases extensively hydrolyze oseltamivir to the active drug oseltamivir carboxylate (OC). The active metabolite, oseltamivir, is a major circulating component (95%) in plasma, and the prodrug oseltamivir accounts for only 5% of the circulating component.
Elimination: Osaletmevir carboxylate is eliminated (>99%) through renal excretion by glomerular filtration and active tubular secretion. The half-life of oseltamivir carboxylate is 6 to 10 hours, while the half-life of oseltamivir is approximately 3 hours.[8]
Available Dosage Forms
Oseltamivir phosphate is administered orally, with or without meals, and is available in capsule form of 3 different dosages (30, 45, and 75 mg) and an oral powder for reconstitution to suspension for pediatric patients. Therapy should be initiated as early as possible, and maximum benefit is derived when started within 48 hours of the onset of illness. However, treatment must be initiated before the 48-hour window for severe illness or patients at risk of complications.
Adult Dosing
Seasonal Influenza A and B Treatment (5-day oral course) [5]
