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INFLUENZA
Treatment Guideline Chart
The clinical spectrum of influenza ranges from asymptomatic infection to primary viral pneumonia that may progress to death.
Patients presenting with influenza-like illness (ie temperature of 37.8ºC, cough and/or sore throat and absence of a known cause other than influenza) might be infected with different types of influenza virus [eg avian influenza (H5N1)] as well as other respiratory pathogens.
A high index of suspicion is needed to recognize influenza in hospitalized patients.
Pneumonia is the most common complication of influenza virus.

Influenza Treatment

Principles of Therapy

  • Initial management of influenza in adults is based on clinical presentation and epidemiological data

Pharmacotherapy

Symptomatic Therapy

Fever and Myalgia

  • May be treated with analgesics (non-opioids) and antipyretics (eg Paracetamol)
  • Avoid salicylates in children ≤18 years of age because of the risk of Reye’s Syndrome

Cough and Colds

  • May be treated with cough and cold preparations (eg expectorants, mucolytics)

Antivirals for Seasonal Influenza

  • Empirical antiviral treatment should be started as soon as possible for all patients with progressive disease highly suspected of influenza, and those at high risk for complications, regardless of illness duration and even without influenza test results 
  • When used within 48 hours of symptom onset, antiviral agents may reduce the duration of symptoms
    • Should not be used if there is uncertainty about diagnosis or if bacterial infection cannot be ruled out
  • Data is limited concerning effectiveness of the antiviral agents for the treatment of patients at high-risk of serious complications of influenza

Baloxavir marboxil

  • The 1st approved influenza virus-specific enzyme polymerase acidic (PA) protein-targeting drug used for the treatment of acute uncomplicated seasonal influenza in patients ≥12 years old who exhibited symptoms for no more than 48 hours
  • Based on several studies, the therapeutic effect of a single dose of Baloxavir marboxil is comparable to that of the 5-day twice-daily treatment with Oseltamivir

M2 Inhibitors

  • Eg Amantadine or Rimantadine
  • Active against influenza A viruses, but not influenza B viruses
  • There continues to be high resistance to adamantanes among influenza A(H3N2) and influenza A(H1N1) pdm09 viruses
    • Thus, Amantadine and Rimantadine are not recommended for treatment and chemoprophylaxis of currently circulating influenza A viruses
  • Effects:
    • As treatment: When used within 48 hours of illness onset in otherwise healthy adults, can reduce duration of uncomplicated influenza
    • As chemoprophylaxis: Both drugs are 70-90% effective in preventing illness from influenza A infection
    • They prevent illness while allowing subclinical infection and the development of protective antibodies; therapy does not interfere with antibody response to vaccine
  • Incidence of CNS side effects is higher among persons taking Amantadine than those taking Rimantadine

Neuraminidase Inhibitors

  • Eg Oseltamivir, Peramivir, Zanamivir
  • Oral Oseltamivir and inhaled Zanamivir are used for the treatment and prophylaxis of infection with influenza A or B viruses
  • IV Peramivir is used for the treatment of influenza A and B viruses especially for those intolerant to oral medications
  • Combination treatment with neuraminidase inhibitors is not recommended
  • Effects:
    • As treatment: Can reduce duration of uncomplicated influenza A and B illness by approximately 1 day compared with placebo when used within 2 days of illness onset
    • Both drugs are effective, 82% Oseltamivir and 84% Zanamivir, in preventing febrile, lab-confirmed influenza illness in otherwise healthy individuals
    • As chemoprophylaxis: Experience in preventing spread of influenza within institutions is limited when compared to the M2 inhibitors

Antivirals for Avian Influenza

  • It is recommended that treatment with a neuraminidase inhibitor is started as early as possible in the clinical course
  • Data regarding the effectiveness of these antiviral medications against H5N1 infections is limited

Oseltamivir

  • Primary antiviral agent of choice for the treatment of influenza A(H5N1) and A(H7N9) virus infections
  • Cultivable virus generally disappears within 2-3 days after initiation of Oseltamivir among avian influenza survivors, although clinical progression has been reported
  • Standard duration of therapy is 5 days but may be extended to 10 days if with no clinical improvement

Other Neuraminidase Inhibitors 

  • Eg Peramivir, Zanamivir
  • Highly active in vitro and in animal models, including that due to Oseltamivir-resistant influenza A(H5N1) virus
  • Orally inhaled Zanamivir has low systemic absorption and may not be useful if extrapulmonary dissemination has occurred; IV Zanamivir may be considered for inpatients with suspected or confirmed resistance to Oseltamivir and Peramivir therapy
  • Early Amantadine treatment of patients with adamantane-susceptible influenza A(H5N1) virus infections in Hong Kong in 1997 may have been associated with clinical benefit
  • Zanamivir monotherapy is associated with rapid emergence of resistance
  • May be used as off-label treatment option in patients with confirmed or strongly suspected infection if Oseltamivir is unavailable especially if the virus is known or likely to be susceptible

M2 Inhibitors (Amantadine, Rimantadine)

  • Early Amantadine treatment of patients with adamantane-susceptible influenza A(H5N1) virus infections in Hong Kong in 1997 may have been associated with clinical benefit
  • Not recommended for patients with avian influenza A(H7N9) virus infection
  • Should only be considered in H5N1 influenza as a treatment option if with treatment failure after neuraminidase inhibitors

Combination Therapy

  • Combinations of Oseltamivir and M2 inhibitors have enhanced antiviral activity and reduced emergence of resistance
  • Demonstrated greater antiviral effects and increased survival compared to monotherapy in animal models
  • Where neuraminidase inhibitors are available:
    • In high-risk exposure groups, including pregnant women, Oseltamivir should be administered as chemoprophylaxis continuing for 7-10 days after the last exposure; Zanamivir could be used in the same way as an alternative
    • In moderate-risk exposure groups, including pregnant women, Oseltamivir might be administered as chemoprophylaxis continuing for 7-10 days after the last exposure; Zanamivir might be used in the same way
    • In low-risk exposure groups and pregnant women, Oseltamivir or Zanamivir should not be administered for chemoprophylaxis
    • Amantadine or Rimantadine should not be administered as chemoprophylaxis

Non-Pharmacological Therapy

  • Rest is recommended
    • Strenuous physical activities (eg running) should be avoided until complete recovery
  • Patients are advised not to go to work or school and to avoid crowded places to reduce transmission
  • Return to full activity gradually after illness has resolved, especially if it has been severe
  • Wear mask in public areas
  • Cover nose/mouth when coughing or sneezing
  • Frequent hand washing
  • Adequate fluid intake is necessary to prevent dehydration
  • Adequate nutrition will assist in recovery
  • Advise patient, if necessary, to stop smoking
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