Washington University Emergency Medicine Journal Club – November 2025
Dr. Brian Cohn
Hello all,
This month we will be looking at literature on the use of Tamiflu (oseltamivir) in the management of influenza infections in both hospitalized and non-hospitalized patients. The PGY-1 and PGY-2 papers will be appraised using the Meta-Analysis form, while the PGY-3 and PGY-4 papers will be appraised using the Therapy form.
Vignette
You’re working an overbooked winter evening shift in the D-pod when triage rolls back your next patient—a 27-year-old previously healthy graduate student whose chief complaint is “flu symptoms.” She looks miserable beneath three hospital blankets, clutching a half-empty sports drink like it’s the last lifeboat on the Titanic.
She tells you that two days ago she attended a “totally chill” study group that turned out to be a viral exchange program. Within 24 hours she developed fever, chills, diffuse myalgias, headache, sore throat, and a cough that makes her reconsider every life decision that led her to higher education. This morning she recorded a temperature of 102.6°F, took some acetaminophen with minimal relief, and ultimately came to the ED after Googling her symptoms and becoming convinced she had either influenza or “early sepsis.”
On exam, she is uncomfortable but not toxic. Vitals show T 101.9°F, HR 108, BP 118/72, RR 18, SpO₂ 98% on room air. Her lungs are clear, she’s mildly tachycardic, and everything hurts “equally and terribly.” A viral swab comes back positive for Influenza A (shocking!!!).
As you swivel back to the computer to place orders for antipyretics and discharge instructions, she asks the question you knew was coming: “So… should I be getting Tamiflu?”
You pause. She’s young, otherwise healthy, and now roughly 48 hours into symptoms. You recall being taught that antivirals shorten illness “by about a day,” but also remember side effects, cost, and a steady stream of skeptical attendings over the years. Does Tamiflu meaningfully reduce symptom duration in patients like her? Does it prevent complications or hospitalizations? Is there a firm cutoff after which it’s no longer useful? And is a positive flu test even necessary to justify treatment? With another febrile patient waiting and flu season in full swing, you find yourself wondering what the more recent literature actually says about oseltamivir’s real-world benefits, prompting your own deep dive into the evidence…
PICO Question
Population: Adult or pediatric patients with suspected or confirmed infection with
influenza, either nonsevere or severe (requiring hospitalization)
Intervention: PO oseltamivir (or other antiviral agents or influenza)
Comparison: Standard of care
Outcome: Mortality, need for hospitalization, morbidity, need for ICU admission,
hospital length of stay, duration of symptoms, time off work/normal activities
Article 1: Gao Y, Zhao Y, Liu M, Luo S, et al. Antiviral Medications for Treatment of
Nonsevere Influenza: A Systematic Review and Network Meta-Analysis. JAMA Intern
Med. 2025 Mar 1;185(3):293-301. [Answer Key].
Article 2: Gao Y, Guyatt G, Uyeki TM, et al. Antivirals for treatment of severe
influenza: a systematic review and network meta-analysis of randomised controlled
trials. Lancet. 2024 Aug 24;404(10454):753-763. [Answer Key].
Article 3: Bai AD, Srivastava S, Al Baluki T, Razak F, Verma AA. Oseltamivir
Treatment vs Supportive Care for Seasonal Influenza Requiring Hospitalization.
JAMA Netw Open. 2025 Jun 2;8(6):e2514508. [Answer Key].
Article 4: Butler CC, van der Velden AW, Bongard E, 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 Jan 4;395(10217):42-52. [Answer Key].
Bottom Line
The risks and efficacy of oseltamivir and other antiviral medications for the management of seasonal influenza infection remains controversial, resulting in poor adherence to clinical guidelines regarding its use. The British Medical Journal itself has detailed issues regarding pharmaceutical industry interference and transparency surrounding many of the initial studies touting the drug’s efficacy.
Two systematic reviews attempted to collate data on antiviral treatment in both nonsevere influenza cases (i.e. non-hospitalized patients) and severe cases (i.e. patients requiring hospitalization). For nonsevere cases, the evidence suggests that the use of antiviral medications in patients with influenza infection within 2 days of symptom onset resulted in a modest reduction in the duration of symptoms by ¾ to 1 day (0.75 days for oseltamivir, 95% CI, 0.57 to 0.93) with no effect on other important outcomes. Oseltamivir was, however, associated with an increased risk of adverse events (relative risk 1.23; 95% CI, 1.10-1.39).
A recently published open-label, pragmatic, randomized controlled trial conducted in 15 European countries came to a similar conclusion, with one important caveat. In this study, oseltamivir treatment was associated with faster recovery by about one day but a 5% increase in nausea and vomiting. Interestingly, although recovery was reported as faster, the number of patients missing usual activities and the number of hours of usual activities missed was similar in both groups. The true benefit and severity of symptoms during the day of reduced symptoms is unclear from this study. There was, again, no significant difference in rates of hospital visits or overnight stays between groups.
For severe cases, the systemic review found that antiviral medications oseltamivir and peramivir were associated with a reduced hospital length of stay by a mean of 1.63 days (95% CI −2.81 to −0.45) and 1.73 days (95% CI −3.33 to −0.13), respectively. No convincing differences in adverse events or serious adverse events were observed for any antiviral medication.
A subsequent large retrospective cohort study of patients hospitalized with severe influenza (Bai 2025) suggested that oseltamivir, when administered within 48 hours of hospital admission in patients with influenza infection, resulted in a decreased in-hospital mortality of 1.4 to 1.8 percent (NNT 56 to 71 to prevent one death) with similar reductions in readmission rates and a more modest reduction in ICU admission. These results are limited by the retrospective nature of this data and the risk of selection bias despite the use of propensity score matching to balance known confounders.
The evidence supporting the use of antiviral medications in patients not requiring hospitalization remains controversial. While these treatments may reduce the duration of symptoms by a little less than a day, they do not seem to reduce time away from usual activities, suggesting symptom severity during this reduced time may be quite mild. In these patients, it seems more reasonable to reserve these medications to those patients considered high risk (see CDC recommendations), though evidence in these subgroups is limited. The evidence supporting use in hospitalized patients is somewhat more convincing, and treatment should be considered in these patients when started within 48 hours of symptoms onset. Some suggest that baloxivir, whose mechanism is different than oseltamivir and other neuraminidase inhibitors, is likely more efficacious, and concerns about increased resistance risk are likely overblown.