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Home » What’s New » Flu Season 2018-2019 

Flu Season 2018-2019 

Most people who get “the flu” have self-limiting symptoms (fever, cough, muscle aches, etc) for about seven to ten days.1 Treatment generally includes rest and supportive measures.2 But some patients have influenza infections that are more serious. There are an estimated 310,000 hospitalizations and up to 56,000 deaths in the U.S. each year due to influenza.3,4 In Canada, there are about 12,200 hospitalizations and 3,500 deaths annually.2 Getting vaccinated each year is the most effective way to prevent influenza infection.2 In certain situations, some patients can also benefit from antiviral medications. There are the neuraminidase inhibitors: oseltamivir, zanamivir, and peramivir; and the newest antiviral, a polymerase acidic endonuclease inhibitor: baloxavir (U.S. only). Avoid inhaled flu vaccine (live) for two weeks prior or 48 hours after antivirals due to possible reduction in vaccine efficacy.5 The following chart provides details for the use of antivirals (prevention and treatment) for influenza.

Abbreviations: AAP=American Academy of Pediatrics; AMMI=Association of Medical Microbiology and Infectious Disease; BID=twice daily; CrCl=creatinine clearance; IV=intravenous

Drug

Dose/Duration (Pediatric)

Dose/Duration (Adult)

Comments

Prevention

Consider preventive antivirals after exposure to an infectious person for patients at high risk of complications from influenza if:1,7

it is within two weeks of receiving an influenza vaccination (i.e., before vaccine is fully effective). poor response to vaccination is expected due to severe immune deficiencies (e.g., receiving immunosuppressants). there are contraindications for vaccination (patients and their close contacts). circulating strains are not covered by the current year’s influenza vaccine.Patients at high risk of complications from influenza include:2

Pregnant women. Those with chronic conditions such as cardiac or pulmonary disorders, diabetes, cancer, renal disease, anemia, neurologic or neurodevelopment conditions, morbid obesity (body mass index [BMI] of 40 or more), and children up to 18 years taking chronic aspirin. Residents of long-term care facilities. Under five years of age. 65 years of age and older. Indigenous persons. Antivirals are generally not recommended for prevention of influenza if more than 48 hours have passed since exposure.1,7

During an outbreak in a healthcare facility, antiviral prevention should be given to all patients regardless of vaccine status, as well as any unvaccinated employees.1 In Canada, if staff are offered antiviral prophylaxis (at the discretion of the local Medical Health Officer), it should be offered to all staff, regardless of vaccine status.12

Oseltamivir (Tamiflu, etc)

FDA- and Health Canada-approved in children 1 year and older.5,6

The AAP and CDC recommend use in infants 3 months and older.1

CDC also suggests use in infants less than 3 months only if critically ill.1

In Canada, the AMMI guidelines do not recommend use in infants less than three months unless they are critically ill.7

3 months to less than 1 year:1,7 3 mg/kg once daily

1 year and older:5,6 15 kg and less: 30 mg once daily >15 kg to 23 kg: 45 mg once daily >23 kg to 40 kg: 60 mg once daily >40 kg: 75 mg once daily

Duration: see comments

13 years and older 75 mg once daily5,6

Renal dosing:5,6 CrCl 61 to 90 mL/min: 75 mg once daily

CrCl 31 to 60 mL/min 30 mg once daily

CrCl 11 to 30 mL/min 30 mg every two days

Hemodialysis:5,630 mg immediately, then 30 mg after alternate dialysis cycles.

Peritoneal dialysis:5,6 30 mg immediately, then 30 mg once weekly.

Duration: see comments

Available as an oral liquid and tablets.5,6

Post-marketing reports of serious skin reactions (e.g., Stevens-Johnson Syndrome) and neuropsychiatric events (e.g., hallucinations, delirium, abnormal behavior, etc).1,5,6,7

Adverse reactions include nausea and vomiting. Taking with food may increase tolerability.6

Not recommended for patients with CrCl less than 10 mL/min who are not on dialysis.5,6

Duration should be at least ten days, or 14 days if the index case is a child or elderly person. Give up to six weeks for community outbreaks and up to twelve weeks for immunocompromised patients.5,6

An injectable product is available in Canada through studies or the Special Access Programme.7

Zanamivir (Relenza)

FDA-approved for 5 years and older.8

Health Canada-approved for 7 years and older.9

10 mg (two inhalations) once daily for ten days.8,9

Give for 28 days for community outbreaks.8,9

10 mg (two inhalations) once daily for ten days.8,9

Give for 28 days for community outbreaks.8,9

Avoid for prophylaxis in patients with pulmonary disease (e.g., asthma, COPD, etc), due to lack of data and risk of bronchospasm.8,9

Post-marketing reports of serious skin reactions (e.g., Stevens-Johnson Syndrome, etc) and neuropsychiatric effects (e.g., delirium, abnormal behavior, etc).9

Allergic reactions with oropharyngeal or facial edema have occurred.1

Contraindicated in milk protein allergy.1,9

Unknown efficacy for long-term care residents and immunocompromised patients.8,9

Baloxavir (Xofluza), U.S. only

Not indicated.14

Not indicated.14

Peramivir (Rapivab)

Not indicated.10,11

Not indicated.10,11

Treatment

Treatment of influenza infections with antivirals is generally not recommended for otherwise healthy patients. Antiviral therapy has been shown to shorten the illness by about one day.1,7

Antivirals are recommended for patients who are hospitalized have severe, complicated, or progressive illness; or are at higher risk for influenza complications, such as:1,2,7

children less than two years (less than five years in Canada). adults 65 years and older. persons with chronic conditions such as pulmonary disease (including asthma), cardiovascular disease (except hypertension alone), renal disease, hepatic disease, hematological disorders (including sickle cell disease), and metabolic disorders (including diabetes mellitus), or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, epilepsy, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury). persons who are immunosuppressed, including those on immunosuppressants and with HIV infection. pregnant or postpartum women (within two weeks after delivery). persons aged younger than 19 years who are on long-term aspirin therapy. American Indians/Alaska Natives/Indigenous persons. persons who are morbidly obese (i.e., body mass index is equal to or greater than 40). residents of nursing homes and other chronic care facilities. In these high-risk patients, antivirals may reduce complications (e.g., otitis media in young children; pneumonia, respiratory failure, etc), mortality in hospitalized patients, and hospital stays in children.1,7

Efficacy is best when antivirals are started within 48 hours of onset of symptoms, but there is some evidence to support starting antivirals within four or five days in patients with severe, progressive, or complicated illness.1,7 In Canada, AMMI guidance for the use of antivirals during a season of potentially low vaccine effectiveness (2017-2018) recommends for high-risk patients to start treatment as soon as possible (ideally within 12 to 24 hours of symptom onset) based on clinical suspicion rather than waiting for diagnostic test results.12

Duration of treatment is generally five days for oseltamivir and zanamivir but can be longer if the patient is severely ill and should be dependent on clinical judgment. Durations of more than five days may be required in patients who are severely or critically ill, have respiratory failure, or are immunocompromised.1,7There are currently no data for use of baloxavir other than as a one-time dose however, there are ongoing trials.14,17,18

Drug

Dose/Duration (Pediatric)

Dose/Duration (Adult)

Comments

Treatment

Oseltamivir (Tamiflu, etc)

FDA-approved: 14 days and older.5

Health Canada-approved: 1 year and older.6

The Canadian AMMI recommend assessing the use of oseltamivir in infants less than 1 year on a case-by-case basis.7

CDC and American Academy of Pediatrics recommend oseltamivir for all ages.1

Less than 1 year, term infants:5 3 mg/kg/dose BID (Also see AAP dosing below)

One year and older:5,6 15 kg or less: 30 mg BID >15 kg to 23 kg: 45 mg BID >23 kg to 40 kg: 60 mg BID >40 kg: 75 mg BID

Duration of treatment: five days.5,6

Based on pharmacokinetic studies, the AAP recommends dosing in infants less than 1 year, term infants:13 0 to 8 months: 3 mg/kg/dose BID 9 to 11 months: 3.5 mg/kg/dose BID

CDC guidelines for premature infants, based on postmenstrual age (i.e., gestational age plus chronological age):1 <38 weeks: 1 mg/kg/dose BID 38 to 40 weeks: 1.5 mg/kg/dose BID >40 weeks: 3 mg/kg/dose BID

(In Canada, the AMMI do not offer specific recommendations for dosing of premature infants.)7

13 years and older:5,6 75 mg BID

Renal dosing:5,6 CrCl 61 to 90 mL/min: 75 mg BID

CrCl 31 to 60 mL/min: 30 mg BID

CrCl 11 to 30 mL/min: 30 mg once daily

Duration of treatment: five days.5,6

Hemodialysis:5,6 Initial dose of 30 mg, then 30 mg after each dialysis, not to exceed three doses over five days for most patients.

Peritoneal dialysis:5,6 30 mg (single dose) prior to dialysis.

Some experts recommend 150 mg BID (if the patient has normal renal function) for immunocompromised or severely ill, hospitalized adult patients.1 However, limited data suggest this increased dose does not improve efficacy.1,6,7 Studies of absorption in critically ill patients show therapeutic levels at regular dosing.1,7

Preferred antiviral for pregnant women.1,7

Product labeling does not recommend for patients with CrCl less than 10 mL/min who are not on dialysis.5,6

May use adult renal dosing in pediatric patients greater than 40 kg.1

Severely ill, hospitalized patients should be treated with oseltamivir (oral or via feeding tube) due to lack of data with inhaled zanamivir and insufficient data with intravenous peramivir.1 In Canada, either oseltamivir or zanamivir can be considered.12

Premature infants may a have slower clearance due to immature renal function.1,7

An injectable product is available in Canada through studies or the Special Access Programme.7

Zanamivir (Relenza)

7 years and older:8,9

10 mg (two inhalations) BID for five days.

10 mg (two inhalations) BID for five days.8,9

Avoid with pulmonary disease (e.g., asthma, COPD, etc) due to lack of data and risk of bronchospasm.8,9

Contraindicated in milk protein allergy.1

No adjustment necessary for renal impairment.

CDC recommends against using inhaled zanamivir in hospitalized patients since there is a lack of data for use in these patients.1 Per AMMI Canada, zanamivir may be considered for patients at high risk of serious influenza complications (e.g., hospitalization or death).12

An injectable product once accessible through investigational or compassionate use is no longer available in North America.1,19

Peramivir (Rapivab)

FDA-approved for children 2 years and older.10

2 to 12 years: 12 mg/kg (up to 600 mg) IV infusion over at least 15 to 30 minutes x one dose.10

Renal dosing:10 CrCl 30 to 49 mL/min: 4 mg/kg x one dose CrCl 10 to 29 mL/min: 2 mg/kg x one dose

Canada: not indicated under 18 years.11

U.S.: 13 years and older; Canada: 18 years and older:10,11

600 mg (3 vials) IV infusion over 15 to 30 minutes x one dose.10,11

Renal dosing:10,11 CrCl 30 to 49 mL/min: 200 mg x one dose CrCl 10 to 29 mL/min 100 mg x one dose

Hemodialysis:10,11 Give after hemodialysis based on renal function.

Generally safe and well tolerated.1 The most common adverse reaction is diarrhea.

Do not mix with other IV meds.10,11

Post-marketing reports of serious skin reactions (e.g., Stevens-Johnson Syndrome, etc), anaphylaxis, and neuropsychiatric events (e.g., hallucinations, delirium, abnormal behavior, etc).10,11

Consider using if a patient cannot tolerate or absorb oral/enteric oseltamivir (e.g., patients with suspected or known gastric stasis, malabsorption, or gastrointestinal bleeding).1

There is limited data in immunocompromised patients, those over 65 years, and those with serious influenza infections requiring hospitalization.10,11 Some limited data in critically

ill hospitalized patients suggest safety (but not efficacy) of 600 mg once daily for five days.1

Baloxavir(Xofluza), U.S. only

FDA-approved: 12 years and older.14

40 kg to less than 80 kg:14Single dose of 40 mg

Avoid taking at the same time as dairy, calcium, iron, magnesium, selenium, and zinc (see comments).14

40 kg to less than 80 kg:14 Single dose of 40 mg

80 kg or more:14 Single dose of 80 mg

Avoid taking at the same time as dairy, calcium, iron, magnesium, selenium, and zinc(see comments).14

Available as an oral tablet.

Generally well-tolerated. The most common adverse effect is diarrhea.14Appears to have less nausea and vomiting than oseltamivir.5,14

Efficacy appears similar to a five-day course of oseltamivir in otherwise healthy patients, 12 to 64 years old, with acute uncomplicated influenza.15 Data is lacking for efficacy of baloxavir in the treatment of oseltamivir-resistant influenza.

There is ongoing study with baloxavir in high-risk patients, as well as in combination with other antivirals for the treatment of hospitalized patients with severe influenza.17,18

No dose adjustments are needed in patients with moderate renal impairment (CrCl of 50 mL and above) or moderate hepatic impairment (Child-Pugh class B). No data available in patients with severe renal or hepatic impairment.14

Resistant strains of influenza have been detected following treatment with baloxavir.16 The clinical implication of this resistance is not yet known. Cross resistance with neuraminidase inhibitors is not expected due to different mechanisms.14

Avoid taking baloxavir at the same time as dairy and products containing calcium, iron, magnesium, selenium, and zinc due to a decrease in baloxavir absorption. Peak baloxavir absorption occurs at four hours.14Consider avoiding dairy and supplements until baloxavir is absorbed.

Preliminary evidence indicates that baloxavir may have a greater reduction in virus levels in respiratory secretions at 24 hours and a shorter duration of virus detection compared to oseltamivir.15 But further study is needed to determine how this might affect transmission of influenza within households or during outbreaks.20

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