Influenza Antiviral Medications: Summary For Clinicians
The information on this page should be considered current for the 2022-2023 influenza season for clinical practice regarding the use of influenza antiviral medications. Clinicians may also wish to consult the IDSA antiviral treatment and antiviral chemoprophylaxis recommendations, and the ATS-IDSA Adult CAP Guidelines.
Trivalent And Quadrivalent Vaccines
There is a range of different influenza vaccines available in Australia1-7, some of which are provided through the National Immunisation Program .8 Trivalent vaccines cover the two influenza A types and a single B lineage whereas the quadrivalent vaccines cover the additional B virus lineage. There is evidence in the transition from trivalent to quadrivalent vaccines that the quadrivalent vaccines confer improved protection without any obvious increase in adverse reactions.9 The standard influenza vaccination for children and adults, including pregnant women, is now a single quadrivalent preparation. An exception to this is children aged six months to nine years who are receiving the vaccine for the first time, and those in the first year after receiving a solid organ or haematopoietic stem cell transplant. These patients should receive two doses at least four weeks apart to induce an optimal immune response.
Table 3 Recommended Oseltamivir And Peramivir Dose Adjustments For Treatment Or Chemoprophylaxis Of Influenza In Adult Patients With Renal Impairment Or End Stage Renal Disease On Dialysis*
* From package inserts for oseltamivir and peramivir see FDA Influenza Antiviral Drugs and Related Information.
Abbreviations: N/A = approved, not recommended1 Renal dosing of oseltamivir is not available in the package insert for pediatric patients. However, these tables may be useful for children who qualify for adult doses based on weight > 40 kg.2 Assuming 3 hemodialysis sessions are performed in the 5- day period. Treatment can be initiated immediately if influenza symptoms develop during the 48 hours between hemodialysis sessions however, the post-hemodialysis dose should still be administered independently of time of administration of the initial dose.3 An initial dose can be administered prior to the start of dialysis.4 Data derived from studies in continuous ambulatory peritoneal dialysis patients.5 Renal dosing from peramivir package insert is available for pediatric patients: Creatinine clearance 50 mL/min: 12 mg/kg Creatinine clearance 30 to 49 mL/min: 4 mg/kg Creatinine clearance 10 to 29 mL/min: 2 mg/kg.
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What Are The Uses Of Antivirals Against Seasonal Influenza
The policy and practice on the use of antivirals varies between European countries. In some countries, using evidence-based policies, antivirals are only recommended for adults who are at increased risk of the complications of flu. They are generally not recommended for otherwise healthy adults with ordinary influenza. Like all medicines they can have side effects in some people.
For people in a risk group the most important way of preventing the serious complications of flu is still the flu vaccine and taking general precautions. However, if you are in a risk group and have contracted the flu, you should seek advice early from your doctor, nurse or pharmacist who can advise you on whether you need to take antivirals as they can shorten the illness or reduce the severity of the symptoms.
Priority Groups For Antiviral Treatment Of Influenza
Antiviral treatment is recommended as soon as possible for any patient with suspected or confirmed influenza who:
- has severe, complicated, or progressive illness or
- is at higher risk for influenza complications.
Clinicians can consider early empiric antiviral treatment of non-high-risk outpatients with suspected influenza based upon clinical judgement, if treatment can be initiated within 48 hours of illness onset.
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Antiviral Drugs Can Be Useful In The Following Settings:
Influenza Virus Prevention And Control Among Specific Populations
Each year, ACIP provides general information regarding the prevention and control of influenza with vaccines.
- COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2021-2022external icon. Pediatrics. 2021 Oct 148:e2021053745. doi: 10.1542/peds.2021-053745.external icon
Below additional guidance on antiviral treatment of influenza and other reports related to prevention and control of influenza among specific populations are available:
- American College of Obstetricians and Gynecologists Committee on Obstetric Practice. ACOG Committee. Opinion No. 732: Influenza Vaccination During Pregnancyexternal icon. Obstetrics & Gynecology. 2018 Apr 131:e109-e114. doi: 10.1097/AOG.0000000000002588. PubMed PMID 29578985
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Resources For Drug Product Information
Information about expanded access regulations, other aspects of drug development and review, and resources about the approval status of drugs and formulations can be found at:
- Electronic Orange Book: This resource can be searched for holders of approved or discontinued marketing applications, especially for drugs that may have more than one source of generic preparations.
- Drugs@FDA: This resource can be searched for approval history and labeling information for approved drugs.
- ClinicalTrials.gov: This website is maintained by the National Institutes of Health as a resource for locating information about clinical trials. Posting a trial on this website does not constitute government endorsement of the trial or the product under study.
When Antiviral Medications Do Not Control The Outbreak
If new cases continue to appear 72 to 96 hours after the start of antivirals, consider the following:
- The new cases could be caused by another organism
- There could be compliance/adherence issues
- Resistance to the antiviral medications may have developed in the circulating strain
In the event that the outbreak is not controlled with antiviral use:
- Consult with the OPH Outbreak Management team to determine if the antiviral agents should be continued
Kidney function/Creatinine Clearance
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What Are The Benefits Of Antiviral Drugs
Antiviral treatment works best when started soon after flu illness begins. When treatment is started within two days of becoming sick with flu symptoms, antiviral drugs can lessen fever and flu symptoms and shorten the time you are sick by about one day. They also may reduce the risk of complications such as ear infections in children, respiratory complications requiring antibiotics, and hospitalization in adults. For people at higher risk of serious flu complications, early treatment with an antiviral drug can mean having milder illness instead of more severe illness that might require a hospital stay. For adults hospitalized with flu illness, some studies have reported that early antiviral treatment can reduce their risk of death.
Benefits From Antiviral Treatment Of Influenza
Flu antiviral drugs can make flu symptoms milder and can shorten duration of illness. Antiviral drugs work best if started soon after getting sick . Early treatment of flu with antiviral drugs also has been shown to reduce the incidence of ear infections and the need for antibiotic treatment in children between 1 and 12 years old. Treatment with antiviral drugs also may reduce more serious flu-related complications like pneumonia and hospitalizations. Studies in both adults and children show that treatment of hospitalized patients can be beneficial in preventing respiratory failure and death.
CDC and the American Academy of Pediatrics recommend antiviral drugs to treat confirmed or suspected flu in children with severe, complicated, or progressive illness, or who are hospitalized with confirmed or suspected flu, as early as possible. Prompt initiation of antiviral treatment also is recommended for children who are at high risk of serious flu complications and who have confirmed or suspected flu of any severity. Children at high risk of flu-related complications include children younger than 5 years old and children of any age with certain chronic health conditions like asthma, diabetes, or heart or lung disease. For more information on the AAP recommendations, visit the AAPs Red Book Online Influenza Resource Page External.
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Use Of Antiviral Medications To Treat Influenza
Outbreaks of influenza occur every year and typically reach epidemic levels at some part of the season. Usually, uncomplicated influenza gets better with or without antiviral treatment but may cause substantial discomfort and limit activities while it lasts.
Many people with uncomplicated influenza use over-the-counter medicines, get rest, and take plenty of fluids to lessen their symptoms. Antiviral drugs available by prescription can reduce the time it takes for symptoms to improve, and some are also used in selected situations to reduce the chance of illness in people exposed to influenza virus. Prompt medical evaluation is important for early treatment of influenza as the antiviral drugs may provide the most benefit for patients who initiate therapy within 48 hours of symptom onset.
Symptoms of influenza may mimic other infections which require different treatment . It is important to be evaluated by a healthcare provider, if symptoms are severe or worsening or if there is an underlying chronic medical condition. Laboratory tests can help detect influenza virus. However, a negative test does not always rule out the possibility of an influenza virus infection, and positive tests do not exclude the possibility of other illnesses or take the place of clinical evaluation.
Treatment Efficacy And Effectiveness Studies
Randomized, controlled trials conducted primarily among persons with mild illness in outpatient settings have demonstrated that zanamivir or oseltamivir can reduce the duration of uncomplicated influenza A and B illness by approximately 1 day when administered within 48 hours of illness onset compared with placebo . One randomized, controlled trial of oseltamivir treatment among 408 children aged 13 years reported that when oseltamivir was started within 24 hours of illness onset, the median time to illness resolution was shortened by 3.5 days compared with placebo . Minimal or no benefit was reported in healthy children and adults when antiviral treatment was initiated more than 2 days after onset of uncomplicated influenza. The amount of influenza viral shedding was reduced among those treated, but studies on whether the duration of viral shedding is reduced have been inconsistent and the temporal and causal relationships between changes in influenza viral shedding and clinical outcomes have not been well-established. One evidence review concluded that neuraminidase inhibitors were not effective in reducing the severity or duration of ILI . However, a variety of pathogens can cause ILI besides influenza viruses, and this review did not conclude that neuraminidase inhibitors were ineffective in reducing laboratory-confirmed influenza among adults .
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Antiviral Drugs Approved For Use In Children
If your childs provider prescribes oseltamivir capsules for your child and your child cannot swallow capsules, the prescribed capsules may be opened, mixed with a thick sweetened liquid, and given that way.
There are four flu antiviral drugs approved by the U.S. Food and Drug Administration for use in the United States which are recommended by CDC for use in children this flu season:
- Oseltamivir is approved for treatment of flu in children 2 weeks old or older. Oral oseltamivir comes in the form of pills and liquid. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of flu in infants younger than 14 days old.
- Zanamivir is approved for treatment of flu in children 7 years and older. It is not recommended for use in children with underlying respiratory disease, including those with asthma and other chronic lung diseases. Inhaled zanamivir is given via a special inhaler .
- Peramivir is given intravenously and recommended for use in children 2 years and older.
- Baloxavir is a pill that is given as a single dose by mouth and is approved for early outpatient treatment of children with flu who are aged 12 years and older.
When Should Antiviral Drugs Be Taken For Treatment
Studies show that flu antiviral drugs work best for treatment when they are started within two days of getting sick. However, starting them later can still be beneficial, especially if the sick person is at higher risk of serious flu complications or is in the hospital with more severe illness. Follow instructions for taking these drugs.
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Circumstances That May Affect Decisions Regarding Use Of Antiviral Medication
- If the resident meets case definition and has been symptomatic for MORE than 48 hours and antiviral treatment has NOT been started, use Appendix A for making decisions about the use of antivirals
- If the outbreak is ongoing when the five-day treatment course ends AND the resident did NOT have lab-confirmed influenza , the resident should be switched to a prophylactic dose until the outbreak is declared over. This is recommended in case of a potential outbreak caused by more than one agent
Should I Still Get A Flu Vaccine
Yes. Antiviral drugs are not a substitute for getting a flu vaccine. While flu vaccine can vary in how well it works, a flu vaccine is best way to help prevent seasonal flu and its potentially serious complications. Everyone 6 months and older should receive a flu vaccine every year. Antiviral drugs are a second line of defense that can be used to treat flu if you get sick.
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What Are The Possible Side Effects Of Antiviral Drugs
Side effects vary for each medication. The most common side effects for oseltamivir are nausea and vomiting. Zanamivir can cause bronchospasm, and peramivir can cause diarrhea. Other less common side effects also have been reported. Your health care provider can give you more information about these drugs or you can check the Food and Drug Administration websiteexternal icon for specific information about antiviral drugs, including the manufacturers package insert.
Parents, if your child gets sick with flu, antiviral drugs offer a safe and effective treatment option. For treatment, influenza antiviral drugs should ideally be started within 2 days after becoming sick and taken according to your doctors instructions .
Questions And Answers About Antivirals
Although vaccination is the preferred option for preventing influenza, antivirals can be useful when the vaccine fails, for example, due to:
antigenic mismatch with circulating virus,
waning immunity in elderly,
the vaccine not yet available, or
during an outbreak of avian influenza or an emerging pandemic.
At least one EU country makes specific recommendations on when to use antivirals according to the levels of circulating influenza viruses as determined by surveillance.
To date there have been few instances of resistance to the neuraminidase inhibitors and resistant viruses that transmit on are very rare. Resistant mutants to the M2 inhibitors have been detected in a number of countries and all current circulating influenza viruses are resistant to M2 inhibitors. Therefore, the use of M2 inhibitors in treatment of influenza is not recommended. Antiviral resistance in Europe is monitored by ECDC and EuroFlu based on the reports sent by influenza reference laboratories to TESSy.
ECDC routinely collects, analyses and disseminates information on antiviral resistance from influenza viruses isolated from all EEA/EFTA countries.
The analysis of resistance against neuraminidase inhibitors and adamantanes is performed by measuring IC50 values and/or by genotyping of viruses for detection of known drug resistance mutations.
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What Antiviral Drugs Are Recommended This Flu Season
There are four FDA-approved antiviral drugs recommended by CDC to treat flu this season.
- oseltamivir phosphate ,
- baloxavir marboxil .
Generic oseltamivirexternal icon and Tamiflu® are available as a pill or liquid suspension and are FDA approved for early treatment of flu in people 14 days and older. Zanamivir is a powder that is inhaled and approved for early treatment of flu in people 7 years and older. is administered using an inhaler device and is not recommended for people with breathing problems like asthma or COPD.) Oseltamivir and zanamivir are given twice a day for 5 days. Peramivir is given once intravenously by a health care provider and is approved for early treatment of flu in people 2 years and older. Baloxavir is a pill given as a single dose by mouth and is approved for early treatment of flu in people 12 years and older. is not recommended for pregnant people, breastfeeding people, outpatients with complicated or progressive illness, or hospitalized patients because there is no information about use of baloxavir in these patients.)
Table 1 Antiviral Medications Recommended For Treatment And Chemoprophylaxis Of Influenza
|Not Recommended for Use in
|Adverse events: nausea, vomiting, headache. Post marketing reports of serious skin reactions and sporadic, transient neuropsychiatric events2
|7 yrs and older3
|people with underlying respiratory disease 3
|Adverse events: risk of bronchospasm, especially in the setting of underlying airways disease sinusitis, and dizziness. Post marketing reports of serious skin reactions and sporadic, transient neuropsychiatric events2
|people with underlying respiratory disease 3
|Adverse events: diarrhea. Post marketing reports of serious skin reactions and sporadic, transient neuropsychiatric events2
|Adverse events: none more common than placebo in clinical trials
|Approved for post-exposure prophylaxis in persons 5 yrs and older6
Abbreviations: N/A = not applicable, COPD = chronic obstructive pulmonary disease.
- Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who:
- is hospitalized *
The following recommendations do not necessarily represent FDA-approved uses of antiviral products but are based on published observational studies and expert opinion and are subject to change as the developmental status of investigational products and the epidemiologic and virologic features of influenza change over time.
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