EPIC-HR was a randomized, double-blind, placebo-controlled clinical trial studying Paxlovid for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Patients were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions.

All patients had not received a COVID vaccine and had not been previously infected with COVID In this analysis, patients received Paxlovid, and patients received placebo, and among these patients, 0.

Benefit of Paxlovid was observed in patients with prior immunity to the virus that causes COVID Among patients in EPIC-HR who were antibody positive at trial enrollment, the risk of COVIDrelated hospitalization or death from any cause during 28 days of follow-up was 0.

EPIC-SR was another clinical trial that enrolled vaccinated patients with at least one risk factor for progression to severe COVID Although not statistically significant, among these vaccinated patients, there was a reduction in the risk of COVID related hospitalization or death from any cause.

EPIC-HR and EPIC-SR were randomized controlled trials and provide information about COVID rebound. Data from these two trials showed that rebound in SARS-CoV-2 RNA or virus shedding or COVID symptoms occurred in a subset of patients and happened in both the patients receiving Paxlovid and the placebo.

The U. If you have mild to moderate COVID symptoms non-hospitalized, not requiring oxygen or an increase in home oxygen you may be eligible for antiviral treatments including oral antivirals or an IV intravenous or in your arm antiviral.

Individuals who are uninsured, rely on Medicare, Medicaid, or VA insurance, or receive care from Indian Health Services can receive free access to COVID and flu testing, telehealth, and treatment through the Home Test to Treat program.

Talk with your doctor or health care provider today. Oral antivirals are pills that stop the virus that causes COVID from making copies of itself in your body. One oral antiviral is called Paxlovid, and the other is called Lagevrio also known as molnupiravir. If you are eligible, start using oral antivirals as soon as possible—no later than 5 days after your first symptoms appear.

These pills are taken at home two times a day for 5 days. Oral antivirals are available with a prescription from a health care provider and through the Test to Treat program. Paxlovid may also be prescribed by a state-licensed pharmacist. Suggested Questions for Your Doctor or Health Care Provider:.

There are no available efficacy, safety, or resistance data for baloxavir monotherapy of influenza in severely immunosuppressed patients and emergence of resistance during treatment is a concern because of prolonged influenza viral replication in these patients.

When indicated , antiviral treatment should be started as soon as possible after illness onset , ideally within 48 hours of symptom onset for the greatest clinical benefit.

However, observational studies have reported that antiviral treatment of influenza can have clinical benefit in patients with severe, complicated or progressive illness, and in hospitalized patients when started after 48 hours of illness onset. Decisions about starting antiviral treatment should not wait for laboratory confirmation of influenza see resources regarding Clinical Description and Lab Diagnosis of Influenza for more information on influenza diagnostic testing.

Clinical benefit is greatest when antiviral treatment is started as close to illness onset as possible. Antiviral treatment with oral oseltamivir, inhaled zanamivir, intravenous peramivir, or oral baloxavir also can be considered for any previously healthy, symptomatic outpatient not at higher risk for influenza complications, who is diagnosed with confirmed or suspected influenza, on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.

The recommended treatment course for uncomplicated influenza is two doses per day of oral oseltamivir or inhaled zanamivir for 5 days, or one dose of intravenous peramivir or oral baloxavir for 1 day.

While influenza vaccination is the best way to prevent influenza illness, a history of influenza vaccination does not rule out the possibility of influenza virus infection in an ill patient with clinical signs and symptoms compatible with influenza.

Figure: Guide for considering influenza testing and treatment when influenza viruses are circulating in the community regardless of influenza vaccination history 1 Complete footnotes for this algorithm are available.

Early antiviral treatment of influenza should be considered for outpatients in these racial and ethnic minority groups 1 Although all children younger than 5 years old are considered at higher risk for complications from influenza, the highest risk is for those younger than 2 years old, with the highest hospitalization and death rates among infants younger than 6 months old.

Treatment Considerations for Patients Hospitalized with Suspected or Confirmed Influenza 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.

For hospitalized patients with suspected or confirmed influenza, initiation of antiviral treatment with oral or enterically administered oseltamivir is recommended as soon as possible.

Antiviral treatment might be effective in reducing morbidity and mortality in hospitalized influenza patients, especially adults, even if treatment is started more than 48 hours after onset of illness. Inhaled zanamivir, oral baloxavir, and intravenous peramivir are not recommended routinely for hospitalized patients with suspected or confirmed influenza because of insufficient data on use of these antivirals showing clinical benefit in hospitalized influenza patients.

There are also insufficient data for treatment of hospitalized influenza patients with intravenous peramivir.

The optimal duration and dosing of antiviral treatment are uncertain for severe or complicated influenza. Treatment regimens might need to be altered to fit the clinical circumstances.

Decisions about extended longer duration of treatment should be guided by clinical judgment in patients whose illness is prolonged. Virologic testing of lower respiratory tract specimens by real-time reverse transcription-polymerase chain reaction RT-PCR can help guide decisions about extended treatment in hospitalized influenza patients with severe and prolonged illness.

Critically ill patients with respiratory failure can have prolonged influenza viral replication in the lower respiratory tract and might benefit from longer duration of treatment.

Longer treatment regimens might be necessary in immunocompromised patients who may have prolonged influenza viral replication. Such patients are at risk of emergence of influenza viruses with reduced susceptibility or antiviral resistance during or after antiviral treatment. A higher dose of oral or enterically administered oseltamivir has been recommended by some experts e.

However, oral or enterically administered oseltamivir at standard doses has been reported to be adequately absorbed in critically ill adults to therapeutic blood levels Ariano, , and available data suggest that higher dosing may not provide additional clinical benefit Abdel-Ghafar, ; Ariano, ; Kumar, ; Lee, ; South East Asia Infectious Disease Clinical Research Network, Studies indicate that exposure to oseltamivir carboxylate the active metabolite of oseltamivir is similar between obese and non-obese subjects for both 75 mg and mg doses given twice daily Ariano, ; Jittamala, ; Pai, ; Thorne-Humphrey, If a hospitalized patient treated with oseltamivir or peramivir manifests progressive lower respiratory symptoms, resistant virus should be considered.

However, clinicians should note that failure to improve or clinical deterioration during oseltamivir or peramivir treatment is more likely to be related to the natural history of acute lung injury and inflammatory damage or onset of other complications e.

Careful attention to ventilator and fluid management and to the prevention and treatment of secondary bacterial pneumonia e. pneumoniae , S. pyogenes , and S. aureus , including MRSA also is critical for severely ill patients Bautista, ; Finelli, ; Hageman, ; Harper, ; Mandell, ; Mauad, ; Shieh, Table 2.

Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis Antiviral Agent.

Antiviral Agent. Oral Oseltamivir. Treatment 5 days 1. Chemoprophylaxis 7 days 5. Inhaled Zanamivir 6. Treatment 5 days. Intravenous Peramivir 7. Treatment 1 day 1. Chemoprophylaxis 8. Not recommended. Oral Baloxavir 9. Treatment 1 day. Chemoprophylaxis 9.

Dosage is the same as to treatment. Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in people 14 days and older, and for chemoprophylaxis with once-daily dosing in people 1 year and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less than 14 days old, and for chemoprophylaxis in infants 3 months to 1 year of age, is recommended by CDC and the American Academy of Pediatrics Recommendations for Prevention and Control of Influenza in Children, — This is the FDA-approved oral oseltamivir treatment dose for infants 14 days and older and less than 1 year old and provides oseltamivir exposure in children similar to that achieved by the approved dose of 75 mg orally twice daily for adults, as shown in two studies of oseltamivir pharmacokinetics in children Kimberlin, [3.

The American Academy of Pediatrics has recommended an oseltamivir treatment dose of 3. It is unknown whether this higher dose will improve efficacy or prevent the development of antiviral resistance.

However, there is no evidence that the 3. Current weight-based dosing recommendations are not appropriate for premature infants. Premature infants might have slower clearance of oral oseltamivir because of immature renal function, and doses recommended for full-term infants might lead to very high drug concentrations in this age group.

See Special Considerations for Institutional Settings section below for details regarding duration of chemoprophylaxis for outbreaks in institutional settings. Daily dosing for a minimum of 5 days was used in clinical trials of hospitalized patients with influenza de Jong, , Ison, There are no data for use of peramivir for chemoprophylaxis of influenza.

Baloxavir marboxil Xofluza [package insert] [ KB, 16 pages]. Baloxavir marboxil should not be administered with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids or oral supplements e.

There are no available published data from clinical trials for baloxavir treatment of influenza in non-hospitalized patients who are pregnant, immunocompromised, or have severe disease. Influenza Antiviral Resistance Considerations Antiviral resistance and reduced susceptibility to the neuraminidase inhibitors and to baloxavir among circulating influenza viruses is currently very low, but this can change.

For weekly surveillance data on susceptibility of circulating influenza viruses to antivirals in the U. this season, see the FluView Weekly U. Influenza Surveillance Report. Influenza viruses with reduced susceptibility or resistance to antivirals can occur sporadically Hurt, ; Takashita, ; Takashita, or emerge during or after antiviral treatment in some patients e.

Oseltamivir resistance in influenza A H3N2 and A H1N1 pdm09 viruses can develop during treatment, particularly in young children Roosenhoff, ; Lina, ; , and immunocompromised persons Memoli, Influenza viruses may become less susceptible or resistant to oseltamivir and peramivir during antiviral treatment with one of these drugs and remain susceptible to zanamivir; this has been reported most often for influenza A H1N1 pdm09 viruses Graitcer, ; Lackenby, ; Memoli, ; Nguyen, ; Nguyen, Human-to-human transmission of influenza A H1N1 pdm09 viruses with an HY mutation in viral neuraminidase conferring resistance to oseltamivir has been reported among severely immunocompromised patients in hospital units, Gooskens, ; Chen, ; and in the community Hibino, ; Le, ; Hurt, ; Hurt, ; Takashita, , but currently appears to be uncommon.

Limited human-to-human transmission of influenza A H3N2 virus with reduced susceptibility to baloxavir has been reported sporadically in Japanese children Takashita, ; Takashita ; Imai, , but currently appears to be uncommon.

Molecular analyses can detect genetic changes in influenza viruses associated with resistance and reduced susceptibility to oseltamivir and peramivir. The CDC Influenza Division is available for consultation regarding antiviral susceptibility testing as needed.

Information about neuraminidase inhibitor susceptibility testing and interpretation of results of neuraminidase inhibition assays is available on the WHO website.

Antiviral Treatment Efficacy and Effectiveness Patients with Uncomplicated Influenza Meta-analyses of randomized controlled clinical trials RCTs have demonstrated efficacy of early initiation of treatment started within 36 to 48 hours of illness onset with neuraminidase inhibitors in reducing duration of fever and illness symptoms compared with placebo in otherwise healthy children and adults with uncomplicated influenza Jefferson, ; Dobson, ; Malosh, ; Liu, One randomized clinical trial in children with uncomplicated influenza demonstrated a modest reduction in duration of symptoms and influenza virus shedding in patients initiating treatment after 48 hours; post hoc analysis suggested that oseltamivir treatment initiated 72 hours after illness onset reduced symptoms by one day compared with placebo Fry, A meta-analysis of RCTs comparing early treatment with oseltamivir to placebo or nonactive controls among adults and adolescents with uncomplicated influenza found no reduction in the risk of subsequent hospitalization with influenza but was underpowered to detect an effect given the very low rate of hospitalization among the trial populations Hanula ; Antoon ; Uyeki RCTs and a meta-analysis of RCTs comparing baloxavir to placebo or oseltamivir among children and adults with uncomplicated influenza found that baloxavir was superior to placebo and comparable to oseltamivir in reducing symptom duration Kuo, ; Portsmouth