The Medical Letter on Drugs and Therapeutics
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ISSUE 1740
ISSUE 1740
October 27, 2025
Issue 1740
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Antiviral Drugs for Seasonal Influenza for 2025-2026
October 27, 2025 (Issue: 1740)
Influenza is generally a self-limited illness, but complications
including pneumonia, respiratory failure, and
death can occur, especially in persons at increased
risk (see Table 1).
- CDC. Influenza antiviral medications: summary for clinicians. December 8, 2023. Available at: https://bit.ly/48KeAna. Accessed October 8, 2025.
- TM Uyeki et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis 2019; 68:895. doi:10.1093/cid/ciy874
- Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2025-2026: policy statement. Pediatrics 2025 July 28 (epub). doi:10.1542/peds.2025-073620
- CDC. Information on interpretation of influenza testing results when virus is circulating for health care settings. August 31, 2020. Available at: https://bit.ly/3KKyWVs. Accessed October 8, 2025.
- JP Metlay et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019; 200:e45. doi:10.1164/rccm.201908-1581st
- CC Butler et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet 2020; 395:42. doi:10.1016/s0140-6736(19)32982-4
- FG Hayden et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018; 379:913. doi:10.1056/nejmoa1716197
- MG Ison et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis 2020; 20:1204. doi:10.1016/s1473-3099(20)30004-9
- MK Doll et al. Safety and effectiveness of neuraminidase inhibitors for influenza treatment, prophylaxis, and outbreak control: a systematic review of systematic reviews and/or meta-analyses. J Antimicrob Chemother 2017; 72:2990. doi:10.1093/jac/dkx271
- J Katzen et al. Early oseltamivir after hospital admission is associated with shortened hospitalization: a 5-year analysis of oseltamivir timing and clinical outcomes. Clin Infect Dis 2019; 69:52. doi:10.1093/cid/ciy860
- Y Sharma et al. Effectiveness of oseltamivir in reducing 30-day readmissions and mortality among patients with severe seasonal influenza in Australian hospitalized patients. Int J Infect Dis 2021; 104:232. doi:10.1016/j.ijid.2021.01.011
- Y Gao et al. Antiviral medications for treatment of nonsevere influenza: a systematic review and network meta-analysis. JAMA Intern Med 2025; 185:293. doi:10.1001/jamainternmed.2024.7193
- J Baker et al. Baloxavir marboxil single-dose treatment in influenzainfected children: a randomized, double-blind, active controlled phase 3 safety and efficacy trial (miniSTONE-2). Pediatr Infect Dis J 2020; 39:700. doi:10.1097/inf.0000000000002747
- RE Malosh et al. Efficacy and safety of oseltamivir in children: systematic review and individual patient data meta-analysis of randomized controlled trials. Clin Infect Dis 2018; 66:1492. doi:10.1093/cid/cix1040
- AD Bai et al. Oseltamivir treatment vs supportive care for seasonal influenza requiring hospitalization. JAMA Netw Open 2025; 8:e2514508. doi:10.1001/jamanetworkopen.2025.14508
- Y Gao et al. Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials. Lancet 2024; 404:753. doi:10.1016/s0140-6736(24)01307-2
- AP Campbell et al. Influenza antiviral treatment and length of stay. Pediatrics 2021; 148:e2021050417. doi:10.1542/peds.2021-050417
- JS Lee et al. Clinical effectiveness of intravenous peramivir versus oseltamivir for the treatment of influenza in hospitalized patients. Infect Drug Resist 2020; 13:1479. doi:10.2147/idr.s247421
- D Kumar et al. Combining baloxavir marboxil with standard-ofcare neuraminidase inhibitor in patients hospitalised with severe influenza (FLAGSTONE): a randomised, parallel-group, double-blind, placebo-controlled, superiority trial. Lancet Infect Dis 2022; 22:718. doi:10.1016/s1473-3099(21)00469-2
- JK Louie et al. Neuraminidase inhibitors for critically ill children with influenza. Pediatrics 2013; 132:e1539. doi:10.1542/peds.2013-2149
- SG Muthuri et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2014; 2:395. doi:10.1016/s2213-2600(14)70041-4
- JK Louie et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09. Clin Infect Dis 2012; 55:1198. doi:10.1093/cid/cis636
- MW Tenforde et al. Timing of influenza antiviral therapy and risk of death in adults hospitalized with influenza-associated pneumonia, influenza hospitalization surveillance network (FluServ-NET), 2012-2019. Clin Infect Dis 2025; 80:461. doi:10.1093/cid/ciae427
- NM Lewis et al. Benefit of early oseltamivir therapy for adults hospitalized with influenza A: an observational study. Clin Infect Dis 2025; 81:190. doi:10.1093/cid/ciae584
- H Ikematsu et al. Baloxavir marboxil for prophylaxis against influenza in household contacts. N Engl J Med 2020; 383:309. doi:10.1056/nejmoa1915341
- Y Zhao et al. Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis. Lancet 2024; 404:764. doi:10.1016/s0140-6736(24)01357-6
- AS Monto et al. Efficacy of baloxavir treatment in preventing transmission of influenza. N Engl J Med 2025; 392:1582. doi:10.1056/nejmoa2413156
- EJ Chow et al. Clinical effectiveness and safety of antivirals for influenza in pregnancy. Open Forum Infect Dis 2021; 8:ofab138. doi:10.1093/ofid/ofab138
- V Ehrenstein et al. Oseltamivir in pregnancy and birth outcomes. BMC Infect Dis 2018; 18:519. doi:10.1186/s12879-018-3423-z
- American College of Obstetricians and Gynecologists. Influenza in pregnancy: prevention and treatment: ACOG Committee Statement No. 7. Obstet Gynecol 2024; 143:e24. doi:10.1097/aog.0000000000005479
- CDC. Recommendations for obstetric health care providers related to use of antiviral medications for the treatment and prevention of influenza. September 15, 2022. Available at: https://bit.ly/3O62Xxx. Accessed October 8, 2025.
- IK Oboho et al. Benefit of early initiation of influenza antiviral treatment to pregnant women hospitalized with laboratory-confirmed influenza. J Infect Dis 2016; 214:507. doi:10.1093/infdis/jiw033
- S Hussain et al. Global update on the susceptibilities of influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2020-2023. Antiviral Res 2025; 241:106217. doi:10.1016/j.antiviral.2025.106217
- AC Hurt et al. Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia. J Infect Dis 2012; 206:148. doi:10.1093/infdis/jis337
- C Renaud et al. H275Y mutant pandemic (H1N1) 2009 virus in immunocompromised patients. Emerg Infect Dis 2011; 17:653. doi:10.3201/eid1704.101429
- JW Tang et al. Transmitted and acquired oseltamivir resistance during the 2018-2019 influenza season. J Infect 2019; 79:612. doi:10.1016/j.jinf.2019.10.020
- R Roosenhoff et al. Viral kinetics and resistance development in children treated with neuraminidase inhibitors: the Influenza Resistance Information Study (IRIS). Clin Infect Dis 2020; 71:1186. doi:10.1093/cid/ciz939
- B Lina et al. Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study. Influenza Other Respir Viruses 2018; 12:267. doi:10.1111/irv.12534
- E Takashita et al. Influenza A(H1N1)pdm09 virus exhibiting enhanced cross-resistance to oseltamivir and peramivir due to a dual H275Y/G147R substitution, Japan, March 2016. Euro Surveill 2016; 21:pii=30258. doi:10.2807/1560-7917.es.2016.21.24.30258
- R Trebbien et al. Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014. Euro Surveill 2017; 22:30445. doi:10.2807/1560-7917.es.2017.22.3.30445
- E Mitha et al. Safety, resistance, and efficacy results from a phase IIIb study of conventional- and double-dose oseltamivir regimens for treatment of influenza in immunocompromised patients. Infect Dis Ther 2019; 8:613. doi:10.1007/s40121-019-00271-8
- T Uehara et al. Treatment-emergent influenza variant viruses with reduced baloxavir susceptibility: impact on clinical and virologic outcomes in uncomplicated influenza. J Infect Dis 2020; 221:346. doi:10.1093/infdis/jiz244
- E Takashita et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill 2019; 24:1900170. doi:10.2807/1560-7917.es.2019.24.12.1900170
- E Takashita et al. Human-to-human transmission of influenza A(H3N2) virus with reduced susceptibility to baloxavir, Japan, February 2019. Emerg Infect Dis 2019; 25:2108. doi:10.3201/eid2511.190757
- M Seki et al. Adult influenza A (H3N2) with reduced susceptibility to baloxavir or peramivir cured after switching anti-influenza agents. IDCases 2019; 18:e00650. doi:10.1016/j.idcr.2019.e00650
- R MacLaren et al. Oseltamivir-associated bradycardia in critically ill patients. Ann Pharmacother 2021; 55:1318. doi:10.1177/1060028020988919
- Peramivir (Rapivab): an IV neuraminidase inhibitor for treatment of influenza. Med Lett Drugs Ther 2015; 57:17.
- Baloxavir marboxil (Xofluza) for treatment of influenza. Med Lett Drugs Ther 2018; 60:193.
- JW Antoon et al. Influenza with and without oseltamivir treatment and neuropsychiatric events among children and adolescents. JAMA Neurol 2025 August 4 (epub). doi:10.1001/jamaneurol.2025.1995
- Influenza vaccines for 2025-2026. Med Lett Drugs Ther 2025; 67:153.
- LA Grohskopf et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices – United States, 2025-26 influenza season. MMWR Morb Mortal Wkly Rep 2025;74:500. doi:10.15585/mmwr.mm7432a2
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