What are the alternatives to Oseltamivir (Tamiflu) for the treatment and prevention of influenza?

Alternatives to Oseltamivir (Tamiflu) for Influenza Treatment and Prevention

For influenza treatment and prevention, the main alternatives to oseltamivir (Tamiflu) include inhaled zanamivir (Relenza), intravenous peramivir (Rapivab), and oral baloxavir marboxil (Xofluza), all of which have activity against both influenza A and B viruses. 1

First-Line Alternative: Zanamivir (Relenza)

• Inhaled zanamivir is considered an equally acceptable alternative to oseltamivir for patients who do not have chronic respiratory disease 1
• Administered via inhalation at a dose of 10 mg (two 5-mg inhalations) twice daily for 5 days for treatment, or once daily for 10 days for chemoprophylaxis 1
• Approved for treatment in patients ≥7 years and for chemoprophylaxis in patients ≥5 years 1
• Like oseltamivir, zanamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day when administered within 2 days of symptom onset 1, 2
• More difficult to administer than oral medications, which may limit its use, especially in children who may not be able to correctly use the inhaler 1

Second-Line Alternative: Peramivir (Rapivab)

• Intravenous peramivir is approved for treatment of acute uncomplicated influenza in non-hospitalized children 2 years and older who have been symptomatic for no more than 2 days 1
• Administered as a single intravenous infusion: 600 mg for adults and adolescents 13-17 years, and 12 mg/kg (up to 600 mg maximum) for children 2-12 years 1
• Useful option for patients who cannot absorb oral medications or tolerate inhaled zanamivir 1
• The efficacy of peramivir in patients with serious influenza requiring hospitalization has not been established 1
• Not recommended for chemoprophylaxis 1

Third-Line Alternative: Baloxavir Marboxil (Xofluza)

• Oral baloxavir is a selective inhibitor of influenza cap-dependent endonuclease, with a different mechanism of action than neuraminidase inhibitors 1
• Administered as a single oral dose based on weight: 40 mg for patients 40-80 kg and 80 mg for patients ≥80 kg 1
• Approved for treatment of uncomplicated influenza in people ≥12 years who have been symptomatic for no more than 48 hours 1
• Advantage of single-dose administration compared to 5-day regimens of other antivirals 1

Important Considerations When Selecting Alternatives

• All neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) and baloxavir have activity against both influenza A and B viruses, unlike older drugs such as amantadine and rimantadine 1, 3, 4
• Treatment should be initiated as early as possible, ideally within 48 hours of symptom onset, to maximize effectiveness 5, 6
• The American Academy of Pediatrics considers oral oseltamivir the antiviral drug of choice for hospitalized children with influenza, with zanamivir as an alternative only for non-hospitalized patients without respiratory disease 1, 5
• For children who cannot take oral medications or use inhalers properly, IV peramivir may be the only viable alternative 1

Efficacy Comparison

• All neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) have similar efficacy in reducing the duration of influenza symptoms by approximately 1-1.5 days when administered within 48 hours of symptom onset 3, 7, 4
• Zanamivir has shown efficacy rates of 84% in preventing febrile, laboratory-confirmed influenza illness when used for prophylaxis, comparable to oseltamivir's 82% 1
• Both zanamivir and oseltamivir have been shown to prevent influenza illness among household contacts when administered after exposure 1, 7

Contraindications and Special Populations

• Zanamivir should not be used in patients with underlying respiratory conditions such as asthma or COPD due to risk of bronchospasm 1
• For pregnant women, oseltamivir remains the preferred agent, though data on alternatives are limited 5
• For infants under 1 year, options are very limited - oseltamivir is the only approved agent, with no approved alternatives 1, 5
• For immunocompromised patients, early treatment with oseltamivir is preferred, but alternatives may be considered if resistance is suspected 5

Antiviral Resistance Considerations

• Continuous monitoring of resistance patterns is conducted by the CDC 1
• In recent seasons, the majority of influenza strains have been susceptible to oseltamivir, zanamivir, and peramivir 1
• High levels of resistance to older drugs (amantadine and rimantadine) persist, so these should not be used unless resistance patterns change significantly 1

Side Effect Profiles

• Zanamivir: Generally well-tolerated; main concern is bronchospasm in patients with underlying respiratory disease 2, 4
• Peramivir: Administered intravenously, which may limit outpatient use; diarrhea is the most common side effect 1
• Baloxavir: Well-tolerated with headache and nausea as the most common side effects 1
• Compared to oseltamivir's common side effect of nausea and vomiting (5% of patients), the alternatives may be better tolerated by some patients 5, 7

When selecting an alternative to oseltamivir, consider the patient's age, ability to use an inhaler, severity of illness, setting (outpatient vs. hospitalized), and presence of underlying respiratory disease to guide the most appropriate choice.