Influenza

Note: Prescribing of oral antiviral agents is authorized ONLY during an epidemic or pandemic declared by the Chief Medical Health Officer for Saskatchewan
Description
  • Influenza is an acute viral respiratory tract infection caused by influenza A or B viruses (family Orthomyxoviridae)
  • Influenza-like illness (ILI) refers to any acute illness having symptoms typical of influenza. Viruses such as adenovirus, parainfluenza or respiratory syncytial virus can cause similar symptoms
  • Influenza causes outbreaks and epidemics worldwide, primarily during the late fall and winter
  • Transmission of the Influenza virus may occur via airborne droplets or by contact or both.
  • Symptoms can be quite incapacitating but for most people influenza is a self-limited infection and resolves without treatment in 4 to 7 days
  • Affects an estimated 10% to 20% of the Canadian population and causes an average of 12,000 hospitalizations and up to 3500 deaths annually
  • Patient groups at higher risk of morbidity and mortality due to influenza include:
    • Asthma, COPD, other chronic pulmonary diseases
    • Cardiovascular disease (excluding hypertension)
    • Malignancy
    • Chronic kidney disease
    • Diabetes mellitus and other metabolic diseases
    • Blood disorders such as anemia
    • Immunosuppression or immunodeficiency due to disease or medication
    • Compromised handling of respiratory secretions – may occur in cognitive dysfunction, spinal cord injury, seizure disorders, neuromuscular disorders, cerebral palsy, etc.
    • Pregnancy
    • Age 65 years or older
    • Children 59 months of age and younger
    • Children < 18 years of age on ASA therapy
    • Obesity - BMI ≥ 40
    • Aboriginal peoples
    • Residents of long-term care and other chronic care facilities
  • Potential complications
    • Pneumonia
    • Otitis media
    • Central nervous system: encephalitis, meningitis, Guillain-Barre syndrome, etc.
    • Musculoskeletal: myositis, rhabdomyolysis
    • Cardiovascular: ischemia, acute coronary syndrome, pericarditis, etc.
    • Toxic shock syndrome
Signs and Symptoms
  • Presentation varies, but in general includes signs and symptoms of upper and/or lower respiratory tract involvement in addition to systemic symptoms
    • Fever (may be slight or absent in children <5 years or adults ≥65 years)
    • Sore throat
    • Myalgias
    • Frontal (forehead) or retro-orbital (behind the eye) headache
    • Nasal discharge
    • Weakness and severe fatigue
    • Cough (non-productive)
    • Tachycardia
    • Red, watery eyes
    • GI symptoms (more common in children less than 5 years)
  • Typical course of influenza: sudden onset of headache, chills and cough followed quickly by fever, appetite loss, muscle aches, and tiredness which can last up to ten days
  • Severity classification:
    • Mild / uncomplicated
      • Fever, cough, sore throat, rhinorrhea, muscle pain, headache, chills, malaise, occasionally diarrhea, vomiting
      • No shortness of breath or worsening of comorbid conditions
    • Moderate / progressive
      • Signs/symptoms above plus chest pain, tachypnea, hypoxia, labored breathing, low blood pressure, confusion, altered mental status, severe dehydration
      • And/or exacerbations of chronic conditions such as asthma, COPD, CKD, diabetes, CVD
    • Severe/complicated illness
      • Lower respiratory tract disease (bronchitis, pneumonia)
      • Encephalitis, encephalopathy (altered mental status, lack of movement coordination, seizures, and coma)
      • Shock, organ failure, myocarditis, rhabdomyolysis
      • Secondary bacterial infection (high fever persisting for more than 3 days)
Differential Assessments

It is difficult to distinguish influenza from other viral infections with similar signs and symptoms, but when influenza is known to be circulating in the community, the likelihood otherwise healthy people presenting with cough and fever > 37.8 have influenza is very high – up to 80 % in adults. However, the following conditions should be ruled out before considering treatment:

  • Common cold – less severe symptoms than influenza (runny nose, sneezing, watery eyes, throat irritation, nasal congestion, etc.) which resolve in a few days. Nasal congestion is uncommon with influenza
  • Allergic rhinitis – persistent upper respiratory tract symptoms such as rhinitis, sneezing, conjunctivitis. Suspect if history of allergic rhinitis, exposure to allergen
  • Acute exacerbation of COPD or asthma  - characterized by change in baseline symptoms beyond normal daily variations that requires change in therapy
  • Sinusitis - persistent purulent nasal secretions, facial tenderness or pain, myalgia uncommon
  • Streptococcal pharyngitis – acute onset of sore throat and fever without cough or other common symptoms of upper respiratory infection
  • Croup – non-productive, barking cough, inspiratory stridor (whistling wheeze), hoarseness, most common in children less than 3 years of age
  • Mononucleosis -  fever, pharyngitis, swollen glands, fatigue with gradual onset and persistent symptoms
  • Pneumonia
    • Primary: Persistent symptoms which worsen instead of resolving - high fever, dyspnea, coughing purulent sputum
    • Secondary bacterial pneumonia: exacerbation of fever, respiratory symptoms after initial improvement
    • Mixed: concurrent viral and bacterial infections
  • Heart failure – cough, shortness of breath, history of heart failure
When to Refer
  • Red flag symptoms – refer patients with these symptoms for emergency or urgent medical assessment and treatment
    • Adults:
      • Respiratory distress -  difficulty breathing, wheezing, chest pain on breathing, hypoxia (cyanosis – bluish skin, nailbeds; tachycardia, tachypnea)
      • Barking cough, stridor (high-pitched musical sound on inspiration, dysphonia (hoarseness)
      • Increased shortness of breath in patients with COPD, asthma, heart failure
      • High fever (>40.5 ° C) or fever lasting for more than 3 days, purulent sputum
      • Lethargy, confusion
      • Severe headache, neck pain or stiffness, photophobia
      • Severe throat pain, dysphagia (difficulty swallowing), drooling
      • Persistent symptoms - no improvement or worsening after 5 days
      • Cough for more than 3 weeks
      • Signs, symptoms of dehydration
      • Patient appears very unwell

    • Infants, Children, Youths
      • Rapid breathing, difficulty breathing
      • Bluish skin colour or change in skin colour
      • Not drinking enough fluids
      • Not waking up or not interacting
      • Confusion, listlessness, altered consciousness
      • Being so irritable that child does not want to be held
      • Symptoms improve but return with fever, worse cough
      • Fever with a rash
      • Seizures
      • Severe or persistent vomiting
      • Severe chest or abdominal pain
Treatment
  • Choice of treatment determined by
    • Severity of symptoms
    • Presence of risk factors
    • Time since symptom onset
    • Level of circulating influenza in community

  •  Rapid Influenza Diagnostic Tests (RIDTs) at point of care
    • Indicated only if results will affect treatment
    • Negative results do not rule out influenza, therefore it must still be considered if typical signs and symptoms of influenza are present especially during peak influenza season
    • Not needed for all patients with signs and symptoms of influenza. Once influenza is known to be active in the area, diagnosis can be based on the presence of typical signs and symptoms


1) Non-pharmacologic treatment

  • Recommend fluids and rest for the patient
  • Reduce spread of virus by:
    • Handwashing or alcohol-based hand rub after contact with eyes, mouth, nose or secretions
    • Cover mouth when coughing or sneezing
    • Staying at home when not feeling well

2) Pharmacologic treatment

A) OTC treatment

    • Analgesics, antipyretics to relieve fever, headache and myalgia
      • Acetaminophen
      • Ibuprofen

B) Prescription therapy

 NOTE - Pharmacist prescribing of oral antiviral agents is authorized ONLY during an epidemic or pandemic declared by the Chief Medical Health Officer for Saskatchewan

  • Antivirals: oseltamivir, zanamivir
    • High rates of resistance to amantadine, therefore not recommended
    • Treatment:
      • May reduce symptom duration by one to two days if treatment is started within 48 hours of symptom onset
      • Ideally should be started within 12 hours of onset
      • May reduce complications of influenza (conflicting evidence)
      • Routine use for mild, uncomplicated influenza symptoms in otherwise healthy children and adults is not recommended
        • Recommend non-pharmacologic and OTC treatments, educate patients on signs and symptoms that would indicate worsening of condition and need for medical attention
      • When appropriate may consider prescribing for mild, uncomplicated symptoms in patients with risk factors if < 48 hours since symptom onset; may be considered in some cases if > 48 hours.
      • Empiric prescribing is appropriate if there is evidence of influenza activity in the community. Check FluWatch http://www.ipac-canada.org/links_flu.php and regional public health offices
      • Refer patients with moderate or severe symptoms as hospitalization is recommended
    • Prophylaxis with antivirals
      • Primary use: outbreak of influenza in long-term care facilities
      • In community, use limited to very immunosuppressed patients if less than 48 hours since their initial exposure to infectious person(s)
      • Duration depends on situation: 2 weeks after post-exposure immunization, 7 to 10 days post-exposure, or for duration of flu season
      • Close monitoring and early initiation of treatment is preferred alternative to prophylaxis post-exposure
      • Antivirals may interfere with response to intranasal live-attenuated vaccine but not to intramuscular inactivated vaccine

 

    •  Antivirals for Influenza:

Medication

Patient group

Treatment
Duration: 5 days

Prophylaxis
Duration variable

Adverse effects/comments

Oseltamivir

Adult and children > 12 years of age

75 mg BID

75 mg once daily

  • Nausea, vomiting, headache
  • Rare - confusion, delirium, hallucinations, and/or self-injury mainly in children (causation not proven)

Children < 12 years of age

3 mg/kg/dose BID

OR as specified below

3mg/kg/dose once daily OR as specified below

< 15 kg (33 lbs)

30 mg BID

30 mg once daily

> 15 to 23 kg (>33 to 51 lbs)

45 mg BID

45 mg once daily

>23 to 40 kg (>51 to 88 lbs)

60 mg BID

60 mg once daily

> 40 kg

75 mg BID

75 mg once daily

Zanamivir

Adults and children > 7 years of age

10 mg (two 5 mg inhalations) once daily

10 mg once daily

Bronchospasm reported, especially in patients with respiratory disease. Not recommended for patients with asthma, COPD

Headache, dizziness, gastrointestinal upset, cough

 

    • Renal dysfunction:
      • No adjustment necessary for zanamivir
      • Dosage modifications for oseltamivir only:

Creatinine clearance (ml/min)

Dose for treatment

Dose for prophylaxis

> 60

75 mg BID

75 mg once daily

>30 to 60

75 mg once daily OR 30 mg BID (suspension, capsule)

75 mg every other day or

30 mg once daily

10 to 30

30 mg once daily

30 mg every other day

< 10 (renal failure)

One 75 mg dose stat

No information

 

3) Pregnancy

  • Pregnancy is a risk factor for severe disease and mortality due to influenza
  • Treat with oseltamivir at standard dose (above) in all trimesters

4) Lactation

  • Women are at high risk for the first 4 weeks post-partum
  • Oseltamivir considered compatible with breastfeeding -  excreted in low levels in milk, not expected to cause any adverse effects in breastfed infants, especially if > 2 month old
  • No data on zanamivir, but it is not well absorbed from the GI tract so would not anticipate any harm to breastfed infants
General Advice / Monitoring
  • Non-pharmacologic +/- OTC treatment of symptoms for all patients
  • Measures to prevent spreading the virus
  • Signs and symptoms of deterioration of condition/when to seek medical attention
    • Breathing becomes rapid and laboured
    • Strange sounds when breathing
    • Confusion, listlessness, altered consciousness
    • Bluish skin colour
    • Not drinking enough fluids
    • Difficulty waking and interacting
    • Child is very irritable but does not want to be held
    • Skin rash with fever
    • Seizures
    • Symptoms return and worsen after initial improvement
    • Symptoms last for more than 7 to 10 days
  • If an antiviral is prescribed
    • Expect an improvement in symptoms within 48 to 72 hours
    • Common side effects  - usually mild
    • Arrange to follow-up with patient in three days
      • Assess for benefit and any side effects; refer if symptoms have not improved or deteriorated.
      • Counsel to finish antiviral, continue symptomatic treatment as needed
Products
Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in RxTx - CPS from CPhA, RxTx (Internet), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).
This information should be routinely consulted before prescribing.

Drug

Oseltamivir

Zanamivir

Prescribing and Billing Details
  • Prescribing of oral antiviral agents is authorized ONLY during an epidemic or pandemic declared by the Chief Medical Health Officer for Saskatchewan
  • Fee pseudoDIN 00951322
  • May prescribe sufficient quantity to treat one episode of influenza
  • Only products with an official indication from Health Canada for influenza and/or recommended by reputable and reliable guidelines are considered for these guidelines. Only the active ingredients in the "products" section are approved for pharmacist prescribing.
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Bowles S, Strang R. Influenza. Compendium of Therapeutic Choices. In: RxTx online database. Available from www.e-therapeutics.ca. (By subscription). Available in Saskatchewan through SHIRP (www.shirp.ca).
  2. Thirion D. Viral rhinitis, influenza, sinusitis and pharyngitis. CT Minor Ailments. In: RxTx online database. Available from www.e-therapeutics.ca. (By subscription). Available in Saskatchewan through SHIRP (www.shirp.ca).
  3. Mansour M. Influenza antiviral treatment and prophylaxis. In: Dynamed online database. Available at https://dynamed.ebscohost.com/ (by subscription).
  4. Antibiotics for streptoccocal pharyngitis. In: Dynamed online database. Available at https://dynamed.ebscohost.com/ (by subscription).
  5. Blondell-Hill E, Fryters S. Bugs & Drugs. Alberta Health Services, 2012.
  6. Anti-infective Review Panel. Seasonal influenza – Treatment for those at risk. In: Anti-infective guidelines for community-acquired infections. Toronto: MUMs Guideline Clearinghouse;2013.
  7. Dolin R. Clinical manifestations of seasonal influenza in adults. In UpToDate online database.  Available at www.uptodate.com (by subscription).
  8. Munoz F. Seasonal influenza in children: Prevention and treatment with antiviral drugs. In UpToDate online database.  Available at www.uptodate.com (by subscription).
  9. Zachary K. Treatment of seasonal influenza in adults. In UpToDate online database.  Available at www.uptodate.com (by subscription).
  10. Aoki F, Upton A, Stiver H et al. The use of antiviral drugs for influenza: A foundation document for practitioners. Can J Infect Dis Med Microbiol 2013;24: Suppl C.
  11. Centers for Disease Control and Prevention. Seasonal influenza (flu). Information for health professionals. Available at http://www.cdc.gov/flu/professionals/index.htm. Accessed April 2016.
  12. Centers for Disease Control and Prevention. Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests. Available at http://www.cdc.gov/flu/professionals/diagnosis/clinician_guidance_ridt.htm. Accessed April 2016.
Developed by medSask, Your Medication Information Service
Posted Feb 2018; Updated Oct 2018