Influenza Medication

  • Author: Robert W Derlet, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Mar 8, 2012
 

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Agents include vaccines and antiviral drugs (ie, amantadine, rimantadine, oseltamivir, zanamivir). The uricosuric agent probenecid may be used as an adjunct to antiviral treatment.

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Antiviral Agents

Class Summary

Antiviral drugs indicated for treatment of influenza include neuraminidase inhibitors (ie, oseltamivir and zanamivir) and amantadine and rimantadine. Neuraminidase inhibitors act directly on the viral proteins, decreasing the virulence of infection.

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Amantadine (Symmetrel)

 

Amantadine is active against influenza A virus. It has little or no activity against influenza B virus isolates. Its mechanism of antiviral action is unclear. It prevents release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is known to prevent virus assembly during virus replication.

Treatment begun within 48 h after the onset of symptoms decreases duration of fever and other symptoms. Amantadine is indicated for both prophylaxis and short-term treatment. Resistant virus strains may develop and be transmitted. It has not been recommended by the Centers for Disease Control and Prevention (CDC) since the 2005-2006 influenza season because of resistance.

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Rimantadine (Flumadine)

 

Rimantadine inhibits viral replication of influenza A virus H1N1, H2N2, and H3N2. It prevents penetration of the virus into the host by inhibiting uncoating of influenza A. Resistant virus strains may develop and be transmitted.

Rimantadine is not recommended by the CDC for seasonal influenza because of resistance. In recent years, laboratory testing by CDC on the predominant strain of influenza (H3N2) circulating in the United States has shown that it is resistant to these drugs.

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Oseltamivir (Tamiflu)

 

Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, oseltamivir decreases the release of viruses from infected cells and thus, viral spread.

Oseltamivir is effective for the treatment of influenza A or B. It must be administered within 48 hours of symptom onset. The sooner it is taken after symptom onset, the better the effect. Oseltamivir reduces the length of illness by an average of 1.5 days. (In a subgroup of high-risk patients, illness was reduced by 2.5 d.) In addition, the severity of symptoms is also reduced. This agent is available as capsules (75 mg, 45 mg, 30 mg) and oral suspension.

Oseltamivir resistance emerged in the United States during the 2008-2009 influenza season. Because of this, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected.

A second-line alternative is a combination of oseltamivir plus rimantadine rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.

The efficacy of oseltamivir against avian influenza is not well established.

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Zanamivir (Relenza)

 

Zanamivir is an inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. This agent is effective against both influenza A and B; its efficacy against avian influenza is not well established.

Zanamivir is inhaled through a Diskhaler oral inhalation device. Circular foil disks that contain 5-mg blisters of drug are inserted into the supplied inhalation device.

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Vaccines

Class Summary

Influenza A and B vaccine is administered each year prior to flu season. The CDC analyzes the vaccine subtypes each year and makes any necessary changes based on worldwide trends.

In April 2007, the US Food and Drug Administration (FDA) approved the first vaccine for H5N1 influenza (ie, avian influenza or bird flu). It is available only to government agencies and for stockpiles.

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Influenza virus vaccine (Afluria, FluLaval, Fluarix, Fluvirin, Fluzone, Fluzone High-Dose, Fluzone Intradermal)

 

Influenza vaccine is indicated for active immunization to prevent infection from influenza A and B viruses. The vaccine induces antibodies specific to virus strains contained in the vaccine. The US Public Health Service determines influenza vaccine contents annually. Typically, 3 live attenuated virus strains, which antigenically represent the influenza strains likely to circulate the next flu season, are included in the formulation each year. Fluzone is approved for children as young as 6 months, whereas Fluvirin is approved for children aged 4 years or older.

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Influenza virus vaccine, intranasal (FluMist, FluMist Quadrivalent)

 

Intranasal influenza vaccine is indicated for active immunization to prevent influenza A and B viruses in healthy children, adolescents, and adults. Each year, the FDA-approved seasonal influenza vaccine includes three strains of influenza virus, two strains of influenza A and one of influenza B. The vaccine induces antibodies specific to virus strains contained in vaccine. The US Public Health Service determines influenza vaccine contents annually. Typically, 3 live attenuated virus strains, which antigenically represent the influenza strains likely to circulate the next flu season, are included in the formulation each year.

The FDA approved a quadrivalent form of the vaccine (FluMist Quadrivalent) in March 2012. Like the already approved FluMist (trivalent), the quadrivalent vaccine contains weakened forms of the virus strains and is administered as a spray into the nose. However, this new formulation includes a second B strain, which increases the likelihood of adequate protection against circulating influenza B strains.

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Influenza virus vaccine (H5N1)

 

The H5N1 inactivated virus vaccine induces antibodies against viral hemagglutinin, thereby blocking viral attachment to human respiratory tract epithelial cells. The vaccine is estimated to reduce the risk of contracting avian influenza by 45%. This vaccine is indicated for active immunization of adults at increased risk of exposure to the H5N1 influenza virus subtype.

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Uricosuric Agents

Class Summary

Agents that inhibit the tubular secretion of the active metabolite of the drug may be used as adjunctive therapy with the antiviral drug oseltamivir.

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Probenecid

 

This agent inhibits tubular secretion of the active metabolite of oseltamivir, reducing the clearance by approximately 50% and approximately doubling systemic exposure to oseltamivir.

The appropriate dosing for combination therapy using probenecid and oseltamivir in the treatment of avian influenza has not been established.

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Contributor Information and Disclosures
Author

Robert W Derlet, MD  Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System

Robert W Derlet, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Association for the Advancement of Science, Infectious Diseases Society of America, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Nicholas John Bennett, MB, BCh, PhD,  Assistant Professor in Pediatrics, Division of Infectious Diseases, Connecticut Children's Medical Center

Nicholas John Bennett, MB, BCh, PhD, is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

Disclosure: Nothing to disclose.

Ethan E Bodle, MD, MPH  Associate Physician, Department of Emergency Medicine, Kaiser Permanente East Bay Medical Center

Ethan E Bodle, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and American Public Health Association

Disclosure: Nothing to disclose.

Joseph Domachowske, MD  Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jon Mark Hirshon, MD, MPH  Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine

Jon Mark Hirshon, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Edmond A Hooker II, MD, DrPH, FAAEM  Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine; Associate Professor, Department of Health Services Administration, Xavier University

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association

Disclosure: Nothing to disclose.

Hien H Nguyen, MD, MS  Associate Clinical Professor, Division of Infectious Diseases and Pulmonary/Critical Care Medicine, Infectious Diseases Consultant and Hospitalist, University of California, Davis, Health System; Medical Director, Acute Infections Management Service, Antimicrobial Infusion Service; Medical Director, Electronic Health Records of University of California, Davis, Health System

Hien H Nguyen, MD, MS is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Frederick Burton Rose, MD, FACP  Professor, Department of Medicine, University Hospital Epidemiologist, State University of New York Upstate Medical University

Frederick Burton Rose, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Christian E Sandrock, MD, MPH, FCCP  Associate Professor of Clinical Medicine, Division of Pulmonary/Critical Care Medicine, Division of Infectious Diseases, Department of Internal Medicine, University of California, Davis Medical Center

Christian E Sandrock, MD, MPH, FCCP is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Infectious Diseases Society of America

Disclosure: Pfizer Honoraria Speaking and teaching; Pfizer Honoraria Consulting; therevance Honoraria Consulting; GSK Honoraria Speaking and teaching

David Yew, MD  Assistant Clinical Professor, Department of Surgery, University of Hawaii, John A Burns School of Medicine; Medical Director and Flight Physician, Hawaii Life Flight, AirMed International

David Yew, MD is a member of the following medical societies: Air Medical Physician Association and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Klaus-Dieter Lessnau, MD, FCCP  Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Joseph F John Jr, MD, FACP, FIDSA, FSHEA  Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Charles V Sanders, MD  Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ruth Lawrence, MD, to the development and writing of the source article.

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Chest radiograph of severe lung disease in a patient with avian influenza.
Global map of countries where avian influenza (bird and human infections) has been reported. Image courtesy of PandemicFlu.gov.
Colorized transmission electron micrograph shows avian influenza A H5N1 viruses (gold) grown in MDCK cells (green). Image courtesy of Centers for Disease Control and Prevention.
Transmission electron micrograph (original magnification 150,000X) shows ultrastructural details of an avian influenza A (H5N1) virion, a subtype of avian influenza A. Note the stippled appearance of the roughened surface of the proteinaceous coat encasing the virion. Image courtesy of Centers for Disease Control and Prevention.
Photograph shows police officers during the 1918 Spanish flu pandemic. Image courtesy of US National Archives.
Avian H5N1 influenza in humans, annual case counts from the World Health Organization.
 
 
 
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