The Medical Letter on Drugs and Therapeutics
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ISSUE
1457
Antiviral Drugs for Seasonal Influenza 2014-2015
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 Select a term to see related articles  acetylsalicylic acid   Amantadine   Aspirin   Flumadine   FluMist   influenza   Neuraminidase inhibitors   Oseltamivir   Peramivir   Relenza   Rimantadine   Tamiflu   Zanamivir 
Revised 1/7/15: Since publication of the Antiviral Drugs for Seasonal Influenza article, peramivir has been approved. We have updated the table to reflect this.

Antiviral drugs can be used for treatment of influenza and as an adjunct to influenza vaccination1 for prophylaxis. Frequently updated information on influenza activity and antiviral resistance is available from the CDC at www.cdc.gov/flu.

NEURAMINIDASE INHIBITORS — Oseltamivir (Tamiflu), which is taken orally, and zanamivir (Relenza), which is inhaled, can be used for chemoprophylaxis and treatment of influenza. When used for prophylaxis after exposure to susceptible strains of seasonal influenza A or B viruses, they have generally been about 70-90% effective.2

In patients with mild illness caused by a susceptible strain of influenza, starting treatment with a neuraminidase inhibitor within 48 hours after the onset of illness can decrease the duration of fever and symptoms and may also reduce the risk of complications such as pneumonia.3 In hospitalized and critically ill patients, observational studies indicate that these drugs can decrease the risk of death when started soon after symptom onset; the results of some studies suggest that treatment within 4-5 days after symptoms appear may still have some benefit.4-6 The usual duration of treatment with a neuraminidase inhibitor is 5 days, but a prolonged treatment course (e.g., 10 days) is often used for critically ill or immunocompromised patients, in whom viral replication may be protracted.

Resistance to oseltamivir can occur,7 especially in immunocompromised patients with prolonged viral shedding, but recently almost all of the circulating influenza A and B viruses tested by the CDC and the World Health Organization have been susceptible to both oseltamivir and zanamivir. The rare oseltamivir-resistant isolates have remained susceptible to zanamivir.

In critically ill patients, oseltamivir capsules can be opened and dissolved in water and given by nasogastric tube.8 An IV formulation of zanamivir is available for hospitalized patients with severe influenza under an emergency investigational new drug request to the manufacturer (GSK: 1-877-626-8019); it has been used successfully to treat some severely ill patients with proven or suspected oseltamivir resistance.9

Peramivir (BioCryst), an investigational IV neuraminidase inhibitor that was available under an emergency use authorization during the 2009-2010 influenza season, has been approved by the FDA for treatment of influenza. A review of peramivir will appear in our February 2, 2015 issue.

Adverse Effects – Nausea, vomiting, and headache are the most common adverse effects of oseltamivir; taking the drug with food may improve its gastrointestinal tolerability. Neuropsychiatric events including self-injury and delirium have occurred in some patients taking neuraminidase inhibitors, particularly children treated with oseltamivir.10 Bronchospasm can occur with inhaled zanamivir; the drug should not be used in patients with underlying airway disease.

Neuraminidase inhibitors administered within 48 hours before or <2 weeks after administration of the intranasal live-attenuated influenza vaccine (FluMist Quadrivalent) may interfere with the vaccine's efficacy. Inactivated influenza vaccine can be given at any time relative to use of a neuraminidase inhibitor.

ADAMANTANES — Amantadine and rimantadine (Flumadine, and generics) have activity against some influenza A viruses, but not against influenza B viruses. They have not been active against most circulating influenza A viruses in recent years and are currently not recommended for treatment or chemoprophylaxis of influenza.

INDICATIONS FOR TREATMENT — Antiviral treatment is recommended as soon as possible for patients with suspected influenza who are at high risk for complications, including children <2 years old, persons <19 years old receiving long-term aspirin therapy, adults ≥65 years old, morbidly obese patients (BMI ≥40), women who are pregnant or ≤2 weeks postpartum, persons of American Indian/Alaska Native heritage, residents of nursing homes and other chronic care facilities, and persons of any age who have certain chronic medical conditions or are immunosuppressed. Treatment is also recommended for patients with suspected or confirmed influenza who show signs of clinical deterioration, develop symptoms of lower respiratory tract infection, or require hospitalization. Antiviral treatment could be considered for previously healthy persons with uncomplicated influenza if it can be started within 48 hours of symptom onset.11

INDICATIONS FOR PROPHYLAXIS — Chemoprophylaxis with antiviral drugs is not recommended for healthy persons exposed to influenza. It can be considered after exposure for persons at high risk of complications who are unvaccinated or unlikely to respond to vaccination or who have received the influenza vaccine within the last 2 weeks, for unvaccinated healthcare workers who are exposed to influenza, and to help control outbreaks in nursing homes. When indicated, chemoprophylaxis should be started within 48 hours after exposure to the virus.

PREGNANCY — Pregnant women are at high risk for complications of influenza, including death.12 Even though oseltamivir and zanamivir are both classified as category C (some fetal toxicity in animals; no adequate studies in pregnant women) for use during pregnancy, prompt treatment with one of these antiviral medications is recommended. Chemoprophylaxis can be considered for women who are pregnant or ≤2 weeks postpartum who have had close contact with someone likely to have been infected with influenza. Oseltamivir appears to be safe for use during pregnancy.13

CONCLUSION — Chemoprophylaxis with antiviral drugs is not recommended for healthy persons exposed to influenza. A neuraminidase inhibitor, either oseltamivir (Tamiflu) or zanamivir (Relenza), remains the drug of choice for treatment of patients with influenza. Oseltamivir is preferred for use in pregnant women and in patients with underlying airway disease.

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  2. AE Fiore et al. Antiviral agents for the treatment and chemoprophylaxis of influenza – recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011; 60:1.
  3. SA Harper et al. Seasonal influenza in adults and children – diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:1003.
  4. JK Louie et al. Neuraminidase inhibitors for critically ill children with influenza. Pediatrics 2013; 132:e1539.
  5. SG Muthuri et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2014; 2:395.
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  7. RE Ariano et al. Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza. CMAJ 2010; 182:357.
  8. QM Le et al. A community cluster of oseltamivir-resistant cases of 2009 H1N1 influenza. N Engl J Med 2010; 362:86.
  9. AH Gaur et al. Intravenous zanamivir for oseltamivir-resistant 2009 H1N1 influenza. N Engl J Med 2010; 362:88.
  10. S Toovey et al. Post-marketing assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: an updated review. Adv Ther 2012; 29:826.
  11. CDC. Influenza antiviral medications: summary for clinicians. Available at www.cdc.gov/flu. Accessed November 21, 2014.
  12. MH Yudin. Risk management of seasonal influenza during pregnancy: current perspectives. Int J Womens Health 2014; 6:681.
  13. M Wollenhaupt et al. The safety of oseltamivir in pregnancy: an updated review of post-marketing data. Pharmacoepidemiol Drug Saf 2014; 23:1035.
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