Essential Evidence

Last Updated on 2022-06-24 © 2022 John Wiley & Sons, Inc.

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Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia

Randall Forsch, MD, MPH, Assistant Professor, University of Michigan
Mark H. Ebell, MD, MS, Professor, College of Public Health, University of Georgia
Kenny Lin, MD, MPH, Professor of Family Medicine, Georgetown University

Overall Bottom Line

  • Yearly influenza vaccination is recommended by ACIP (US) for persons over the age of 6 months. A
  • Patients classically present with rapid onset of fever, cough, chills or rigors, sore throat, and myalgias. A clinical decision rule can be used to identify patients at low, moderate or high risk of influenza. B
  • Rapid antigen tests are most useful during the beginning and end of the flu season. C
  • Treatment is largely supportive; antiviral medications are recommended only if the likelihood of influenza is high and the patient presents within 24 hours of symptom onset. There is no evidence that they reduce serious complications or hospitalization. A
  • Predictors of adverse outcome in the elderly include increased age, previous hospitalization, comorbidities, gender, and number of outpatient visits in the previous year (Table 1). A


Bottom Line

  • Treatment is largely supportive with analgesics, antipyretics, rest, adequate (but not excessive) hydration, and reevaluation if symptoms worsen. C
  • Antiviral medications (oseltamivir, baloxavir, or zanamivir) are recommended only if the probability of influenza is high (see Figure 1) and patients present within 24 or at most 36 hours of symptoms onset. It is also recommended for pregnant patients and for hospitalized patients. 80A 19 20 21 22 23 88
  • Oseltamivir has not been shown in RCTs to reduce the likelihood of hospitalization or the likelihood of complications requiring antibiotics. 64 Studies in patients with cardiopulmonary disease or in patients over age 65 years did not find a signficant reduction in the duration of symptoms. A 52

Drug Therapy

  • When given within 24 hours of the onset of symptoms, antiviral agents such as oseltamivir or zanamivir reduce the duration of symptoms by about 30 hours and may reduce the intensity somewhat. 27 63 64 When given at 24 to 36 hours, it reduces duration by 14 hours. The overall reduction in the ITT population was 21 hours. 18 20 22 52  A Cochrane review using ITT data also found a 21 hour reduction in symptoms. 54
  • There is no evidence from RCTs that oseltamivir reduces the likelihood of hospitalization 54 52 or the likelihood of complications requiring antibiotics, once acute bronchitis is excluded as a complication. 52 The likelihood of pneumonia was reduced by 0.9%, but only in patients with PCR or culture confirmed influenza, and not in the intention to treat population. Studies in patients with cardiopulmonary disease or in patients over age 65 years did not find a signficant reduction in the duration of symptoms. Much of these data were initially unpublished and analysis was based on unpublished clinical trial reports. 52 The drugs are associated with an increased risk of nausea (NNH = 28) and vomiting (NNH = 22). 54
  • 2 RCTs comparing baloxavir with oseltamivir or placebo found a similar reduction in symptoms between oseltamivir and baloxavir compared to placebo (about 20-24 hours), with a greater benefit if given in the first 24 hours (33 hours fewer symptoms) than at 24 to 48 hours (13 hours). This is also similar to oseltamivir. Complications were not reported. 80 88
  • Usual dosing in adults is oseltamivir 75 mg po twice daily for 5 days, baloxavir 40 mg (< 80 kg) or 80 mg (> 80 kg) in a single dose, or zanamivir 10 mg by MDI bid for 5 days.
  • A study randomized 366 hospitalized patients with severe influenza to baloxavir plus oseltamivir, zanamivir or peramivir, or to oseltamivir, zanamivir, or peramivir alone. There was no difference in time to symptom improvement (97.5 vs 100 hours) or any other outcomes. 89
  • A Cochrane review found that amantadine and rimantadine were both effective for the prevention and treatment of influenza symptoms. However, the drugs have significant adverse effects (especially amantadine) and widespread resistance exists. 55 They should not be used routinely in practice, based on current CDC recommendations.
  • A Cochrane review identified one RCT and 29 observational studies of corticosteroids for influenza. The RCT was too small to provide useful information. In the observational studies, there was an association with increased mortality but this could represent residual confounding and confounding by indication, as sicker patients and patients with ARDS or other complications were preferentially given corticosteroids. 79
  • In hospitalized patients with flu and a pulmonary infiltrate, an RCT found that adding clarithromycin and naproxen reduced 30 day mortality (0.9% vs. 8.2%; p = 0.01; NNT = 14) and 90-day mortality. 74
  • A randomized trial randomized 633 patients with influenza who were at inreased risk of complications to either the combination of oseltamivir, amantadine, and ribavrin or to oseltamivir alone. There was some reduction in viral shedding with the combination therapy, but no reduction in influenza symptom severity or duration. There was no difference in adverse events. 76

Complementary/Alternative Therapy

  • Two poor-quality RCTs provide insufficient evidence to recommend "Ganmao" or "E Shu You" Chinese herbal medicines for influenza. 17
  • Two poor-quality RCTs found a small benefit to the homeopathic drug oscillococcinum; current evidence is insufficient to recommend this intervention routinely. 16

Other Treatment

  • Treatment generally includes rest, fluids, and antipyretics. "Forcing fluids" is not supported by any clinical studies and may lead to hyponatremia, especially in infants and the elderly. 14
  • Supplemental oxygen or mechanical ventilation may be needed for hospitalized patients.

Management of Complications

  • In a cohort study of 343 Welsh patients with influenza, complications included bronchitis (19%; 95% CI, 15%-23%), pneumonia (2.9%; 95% CI, 1.4%-5.4%), otitis media (2.3%; 95% CI, 1.0%-4.6%). 12 See those chapters for management of those conditions.
  • Influenza may also worsen cardiac disease and diabetes mellitus control in affected individuals. 11In a U.S. cohort study, up to 12% of adults hospitalized with laboratory-confirmed influenza from 2000 to 2018 experienced acute heart failure or acute coronary syndrome. 87