eMedicine Specialties > Infectious Diseases > Viral Infections
Influenza: Treatment & Medication
Updated: Aug 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- As with other diseases, prevention of influenza is the most effective strategy.
- The CDC has published recommendations for high-risk groups, including all health care personnel, who should be vaccinated.
- Amantadine and rimantadine have been approved for many years for use against influenza A. However, since the fall of 2005 to the present, amantadine and rimantadine are no longer recommended by the CDC because significant resistance has evolved against these two drugs.
- Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009 influenza season.
- The CDC has issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data from a limited number of states indicate a high prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu). 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.
- Influenza A viruses, including two subtypes (H1N1) and (H3N2), and influenza B viruses currently circulate worldwide, but the prevalence of each can vary among communities and within a single community over the course of an influenza season. In the United States, 4 prescription antiviral medications (oseltamivir, zanamivir, amantadine, rimantadine) are approved for treatment and chemoprophylaxis of influenza. Since January 2006, the neuraminidase inhibitors (oseltamivir, zanamivir) have been the only recommended influenza antiviral drugs because of widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2) virus strains. The neuraminidase inhibitors have activity against influenza A and B viruses, while the adamantanes have activity against only influenza A viruses.
- In 2007-2008, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses worldwide. During the 2007-2008 influenza season, 10.9% of H1N1 viruses tested in the United States were resistant to oseltamivir. Complete recommendations are available from the CDC.
- Many physicians in primary care offices or the ED have not used these medications widely.
- Disadvantages of these drugs include lack of efficacy against influenza B, potential adverse effects, and rapid development of viral resistance.
- Two newer drugs have been recently marketed for treatment of influenza A and B. These are the neuraminidase inhibitors oseltamivir and zanamivir.
- Oseltamivir is taken orally (75 mg bid), and zanamivir is taken via an inhalation apparatus (10 mg bid for 5 d).
- Multiple studies have demonstrated their efficacy. These agents work by inhibiting influenza virus neuraminidase, a glycoprotein spike that protrudes from the virus envelope; this spike is needed for successful cellular release of virus and transmission within the body. To be effective, these new agents must be administered within 40 hours of symptom onset.
- Recent studies also demonstrate the efficacy of these agents in preventing influenza A and B, an exciting expansion in their use. The prophylactic dose is one half the acute treatment dose.
- Neuraminidase inhibitors have several advantages over amantadine, including less evolution of resistance, efficacy against influenza B, fewer adverse effects, and dramatic reduction in symptoms, even in patients who have a full course of influenza.
- In a study of 445 patients by the Management of Influenza in the Southern Hemisphere Trialists (MIST) group 1, zanamivir was administered to one half of patients and placebo to the others within 36 hours of symptom onset. Duration of the flu was reduced by 1.5 days in normal-risk groups and 2.5 days in high-risk groups. A significant decrease in the severity of illness in patients treated with zanamivir allowed them to resume normal activities much sooner.
- A study by Treanor et al compared oseltamivir with placebo.5 This analysis included patients with laboratory-based diagnoses of influenza and those with clinical diagnosis based on symptoms. The 629 patients were enrolled and randomized into 1 of 3 treatment arms: (1) standard-dose oseltamivir, (2) high-dose oseltamivir, and (3) placebo. In both oseltamivir groups, the mean illness duration was reduced from 103 to 70 hours. The symptom severity decreased in the treated group by 40%.
- Additional studies analyzed the effect of neuraminidase inhibitors both in acute disease and in prevention.
- In one of these studies, 837 relatives of family members infected with influenza were treated prophylactically with either placebo or zanamivir.6 While 20% of the placebo group became ill, only 4% of the drug-treated group became ill. In addition, this study provided treatment to the index case family member, resulting in a 2.5-day reduction in illness over placebo. Recombinant DNA viral sequences were performed in this study, and no resistant influenza strains developed.
- A novel study analyzed the effects of oseltamivir in experimentally induced influenza in humans.7 In a controlled laboratory environment, volunteers were inoculated intranasally with influenza A/Texas/36/91 (H1N1). One group was administered oseltamivir 26 hours before virus inoculation and another group was administered 28 hours after inoculation. In the prophylactic group, 38% of patients developed influenza, which 67% in the placebo group developed influenza. In the posttreatment group, the duration of illness was reduced from 95 to 53 hours and the severity was reduced by 50% compared with placebo.
- Another study by Hayden et al analyzed 1559 healthy nonimmunized patients who were treated with either placebo or oseltamivir for 6 weeks.8 At the end of the period, 4.8% of the placebo group had laboratory-confirmed influenza, compared with only 1.2% of the oseltamivir group.
- Ongoing studies are analyzing both treatment efficacy and the preventive effects of neuraminidase inhibitors.
- Whether to prescribe one of the newer neuraminidase inhibitors should depend on the patient, the probable type of influenza involved (A or B), and the potential benefit.
- Advantages for prescribing these agents include significantly reducing illness severity and duration. In elderly and high-risk patients who receive these agents, the secondary complications of influenza are also decreased.
- Disadvantages include potential adverse effects and costs. Some patients may be willing to pay $100 to have a less severe episode of the flu. Adverse effects include potential bronchospasm with inhaled zanamivir and nausea, vomiting, and headache from oseltamivir. The bronchospasm associated with zanamivir has received attention from national media. Until more data are available, physicians should not prescribe zanamivir to patients prone to bronchospasm.
- Although oseltamivir is approved for use up to 48 hours after the initiation of symptoms, one study suggested that the most significant effect occurs when taken within 6 hours of symptom onset and only limited effects when therapy is begun more than 24 hours after symptom onset.
Consultations
Consultation with an infectious disease specialist is prudent in some cases.
Activity
Patients with influenza generally benefit from bedrest. Most patients with influenza recover in 3 days; however, malaise may be present for weeks.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Antiviral agents
Drugs indicated for treatment of influenza include neuraminidase inhibitors (ie, oseltamivir and zanamivir) and amantadine and rimantadine.
Oseltamivir (Tamiflu)
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, decreases release of viruses from infected cells and thus, viral spread. Effective to treat influenza A or B. Must administer within 48 h of symptom onset. The best effect occurs the sooner it is taken after symptom onset. Reduces the length of illness by an average of 1.5 d. (In a subgroup of high-risk patients, illness was reduced by 2.5 d.) In addition, the severity of symptoms is also reduced.
Oseltamivir (Tamiflu) resistance has emerged in the United States during the 2008-2009 influenza season. The CDC has issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Preliminary data from a limited number of states indicate a high prevalence of influenza A (H1N1) virus strains resistant to oseltamivir (Tamiflu). 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.
Adult
Acute illness: 75 mg PO bid for 5 d
Prophylaxis: 75 mg PO qd
Pediatric
Acute illness
>1 year and <15 kg: 30 mg PO bid
15-23 kg: 45 mg PO bid
23-40 kg: 60 mg PO bid
>40 kg: Administer as in adults
Prophylaxis
>13 years: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment, chronic cardiac or respiratory disease, and breastfeeding
Zanamivir (Relenza)
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. Effective against both influenza A and B.
To be inhaled through Diskhaler oral inhalation device. Circular foil discs that contain 5-mg blisters of drug are inserted into supplied inhalation device.
Adult
5-mg oral inhalation bid for 5 d
Pediatric
<7 years: Not established
>7 years: Administer as in adults
None reported
Documented hypersensitivity; obstructive airway disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor respiratory status; caution in breastfeeding
Vaccine
Influenza A 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). The approval was based on one multicenter, randomized, double-blinded, placebo-controlled, dose-ranging study in healthy adults aged 18-64 years. The trial investigated the safety and immunogenicity of the vaccine. A total of 103 healthy adults received a 90-mcg dose of the vaccine via IM injection, followed by another 90-mcg dose 28 days later. In addition, approximately another 300 healthy adults received the vaccine at doses lower than 90 mcg, and a total of 48 received placebo by injection. Of the various doses tested, the study showed that the 90-mcg 2-dose regimen provided the better immune response and produced levels of antibodies expected to reduce the risk of acquiring H5N1 influenza in 45% of those who received it.
Influenza virus vaccine (Fluarix, Fluvirin, Fluzone)
Indicated for active immunization to prevent influenza A and B viruses. Induces antibodies specific to virus strains contained in vaccine following administration. 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 age 6 mo, whereas Fluvirin is approved for children aged 4 years or older.
Adult
0.5 mL IM for 1 dose each year prior to flu season
Pediatric
<6 months: Not established
6-35 months (Fluzone): 0.25 mL IM once; administer 2nd dose 4 wk after first dose for vaccine-naïve children
3-8 years: 0.5 mL IM once; administer 2nd dose 4 wk after first dose for vaccine-naïve children
>8 years: 0.5 mL IM for 1 dose each year prior to flu season
Fluviron: <4 years: Not established
Fluarix: <18 years: Not established
Immunosuppressive therapy (eg, high-dose corticosteroids, chemotherapy) may reduce antibody response
Documented hypersensitivity to vaccine contents including thimerosal, eggs, egg products, or chicken protein; history of Guillain-Barré syndrome; history of neurologic symptoms following vaccination
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Defer vaccination with acute febrile illnesses or neurological findings until symptoms have abated; may cause soreness at injection site, fever, malaise, and myalgia
Influenza virus vaccine, intranasal (FluMist)
Indicated for active immunization to prevent influenza A and B viruses in healthy children, adolescents, and adults. Induces antibodies specific to virus strains contained in vaccine following administration. 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.
Adult
0.2 mL intranasally (ie, 1 mL in each nostril) once per season
>49 years: Not established
Pediatric
<2 years: Not established
2-8 years NOT previously vaccinated with intranasal influenza vaccine: 0.2 mL intranasally (ie, 1 mL in each nostril), then repeat dose in 46-74 d
2-8 years previously vaccinated with intranasal influenza vaccine: 0.2 mL intranasally (ie, 1 mL in each nostril) once per season
>8 years: Administer as in adults
Do not administer to children or adolescents receiving aspirin (may increase Reye Syndrome); do not administer until 48 h following discontinuing antiviral agents, and do not initiate antiviral agents for 2 wk following vaccine administration; no data regarding coadministration with other intranasal drugs
Documented hypersensitivity to vaccine contents, including egg or egg protein; children or adolescents receiving aspirin therapy; Guillain-Barré history; known or suspected immune deficiency conditions, including those secondary to immunosuppressive therapies; asthma or reactive airway diseases
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
For nasal use only; thaw prior to use; may increase cough, rhinorrhea, and nasal congestion following second dose in children; may cause cough, runny nose, or sore throat in adults
Influenza virus vaccine, H5N1
Inactivated virus vaccine. Induces antibodies against viral hemagglutinin in vaccine, thereby blocking viral attachment to human respiratory tract epithelial cells. Estimated to reduce risk of contracting avian influenza by 45%. Indicated for active immunization of adults at increased risk of exposure to H5N1 influenza virus subtype.
Adult
18-64 years: Administered as 2-dose regimen; 1 mL (90 mcg) IM on day 1, then repeat dose once on day 28
Pediatric
<18 years: Not established
>18 years: Administer as in adults
Immunosuppressive therapies (eg, high-dose corticosteroids, transplant antirejection medication, antineoplastic agents) may reduce immune response to vaccine
None known
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Data limited; common adverse effects include pain and tenderness at injection site, headache, malaise, and myalgia; do not mix with other vaccines in same syringe; avoid in pregnant or breastfeeding women because of insufficient data in these populations
More on Influenza |
| Overview: Influenza |
| Differential Diagnoses & Workup: Influenza |
 Treatment & Medication: Influenza |
| Follow-up: Influenza |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
HHS Declares Public Health Emergency for Swine Flu. US Department of Health and Human Resources. Available at http://www.hhs.gov/news/press/2009pres/04/20090426a.html. Accessed April 27, 2009.
WHO. Influenza A (H1N1): Special Highlights. World Health Organization. Available at http://www.who.int/en/. Accessed June 11, 2009.
Guidance for Clinicians and Public Health Professionals. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/swineflu/guidance. Accessed April 27, 2009.
Steininger C, Popow-Kraupp T, Laferl H, et al. Acute encephalopathy associated with influenza A virus infection. Clin Infect Dis. Mar 1 2003;36(5):567-74. [Medline].
Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. Feb 23 2000;283(8):1016-24. [Medline].
Hayden FG, Gubareva LV, Monto AS, et al. Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group. N Engl J Med. Nov 2 2000;343(18):1282-9. [Medline].
Hayden FG, Treanor JJ, Fritz RS, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. Oct 6 1999;282(13):1240-6. [Medline].
Hayden FG, Atmar RL, Schilling M, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. Oct 28 1999;341(18):1336-43. [Medline].
[Guideline] Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. Jul 31 2009;58:1-52. [Medline]. [Full Text].
[Best Evidence] Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. Jul 15 2009;200(2):172-80. [Medline].
Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med. May 14 1998;338(20):1405-12. [Medline].
Bridges CB, Fukuda K, Cox NJ, et al. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Apr 20 2001;50(RR-4):1-44. [Medline]. [Full Text].
British Medical Journal Group. Influenza. In: BJM Clinical Evidence Handbook. Fall. London: BMJ Publishing Group; 2008:273-6.
Centers for Disease Control and Prevention (CDC). Update: influenza activity--United States, March 5-11, 2006. MMWR Morb Mortal Wkly Rep. Mar 24 2006;55(11):311-3. [Medline].
Christenson B, Pauksen K, Sylvan SP. Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity. Virol J. Apr 28 2008;5:52. [Medline].
Cunha BA. Amantadine May be Lifesaving in Severe Influenza A. Clin Infect Dis. 2006;43:1574-1575.
Cunha BA. The Clinical Diagnosis of Severe Viral Influenza. Infection. 2008;36:92-93.
Gambotto A, Barratt-Boyes SM, de Jong MD, et al. Human infection with highly pathogenic H5N1 influenza virus. Lancet. Apr 26 2008;371(9622):1464-75. [Medline].
Gross PA, Hermogenes AW, Sacks HS, et al. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med. Oct 1 1995;123(7):518-27. [Medline].
Gubareva LV, Kaiser L, Matrosovich MN, et al. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. Feb 15 2001;183(4):523-31. [Medline].
[Best Evidence] Jefferson T, Rivetti A, Harnden A, et al. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. Apr 16 2008;CD004879. [Medline].
Linder JA. Influenza-associated deaths among children. N Engl J Med. Mar 23 2006;354(12):1317-8; author reply 1317-8. [Medline].
Medical Letter. Rapid diagnostic tests for influenza. Med Lett Drugs Ther. Dec 17 1999;41(1068):121-2. [Medline].
Medical Letter. Two neuraminidase inhibitors for treatment of influenza. Med Lett Drugs Ther. Oct 8 1999;41(1063):91-3. [Medline].
Cunha BA. Pneumonia Essentials. 2nd Ed. Royal Oak, MI: Physician Press; 2008.
Simmons C, Farrar J. Insights into inflammation and influenza. N Engl J Med. Oct 9 2008;359(15):1621-3. [Medline].
Smee DF, Wong MH, Bailey KW, et al. Activities of oseltamivir and ribavirin used alone and in combination against infections in mice with recent isolates of influenza A (H1N1) and B viruses. Antivir Chem Chemother. 2006;17(4):185-92. [Medline].
Smith GJ, Fan XH, Wang J, et al. Emergence and predominance of an H5N1 influenza variant in China. Proc Natl Acad Sci U S A. Nov 7 2006;103(45):16936-41. [Medline].
Storch GA. Diagnostic virology. Clin Infect Dis. Sep 2000;31(3):739-51. [Medline].
Subbarao K, Klimov A, Katz J, et al. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science. Jan 16 1998;279(5349):393-6. [Medline].
Swine flu illness in the United States and Mexico – update 2. World Health Organization. Available at http://www.who.int/en. Accessed April 27, 2009.
Swine Influenza (Flu). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/swineflu. Accessed April 27, 2009.
The MIST Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Lancet. Dec 12 1998;352(9144):1877-81. [Medline].
Treanor J, Falsey A. Respiratory viral infections in the elderly. Antiviral Res. Dec 15 1999;44(2):79-102. [Medline].
Further Reading
Additional resources on influenza are available at Medscape's Influenza Resource Center.
Keywords
influenza, flu, influenza virus, flu virus, influenzavirus, influenza A, influenza B, influenza C, influenza A subtype H3N2, H1N1, H5N1, H9N2, avian influenza, avian flu, bird flu, upper respiratory tract infection, URTI, severe acute respiratory syndrome, SARS, flu pandemic, Orthomyxoviridae, respiratory syncytial virus, RSV, West Nile virus
