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Am Fam Physician. 2019;100(12):online

Clinical Question

Is baloxavir (Xofluza) a safe and effective for treatment of influenza?

Bottom Line

Baloxavir has similar efficacy to oseltamivir (Tamiflu) (33-hour reduction in duration of symptoms compared with placebo) and, like oseltamivir, is most effective when given within 24 hours of the onset of symptoms. If given 24 to 48 hours after symptom onset, symptom duration was reduced by only 13 hours (which is almost identical to what we found in our meta-analysis of oseltamivir [Fam Pract. 2013;30(2):125–133]). It does not seem worth the extra cost in the United States: $160 for baloxavir vs. $50 for oseltamivir ( There are no data regarding the effect on complications or mortality, nor any data for patients younger than 12 years, older than 64 years, or with serious comorbidities. The major advantages of baloxavir over oseltamivir for those who choose to use it are convenience because it is a single dose and fewer adverse drug reactions (number needed to treat = 25). (Level of Evidence = 1b)


Baloxavir inhibits polymerase acidic protein, which is involved in viral replication. This report summarizes the results of a phase two (dose-ranging) trial and a phase three trial comparing baloxavir with oseltamivir and placebo (baloxavir is now U.S. Food and Drug Administration approved). We will focus on the phase three trial, which recruited patients 12 to 64 years with an influenza-like illness for less than 48 hours. The authors randomized patients 20 to 64 years of age into one of three groups in a 2:2:1 ratio: baloxavir in a single dose (40 mg for patients weighing less than 80 kg [176 lbs] and 80 mg for patients weighing at least 80 kg); oseltamivir, 75 mg twice daily for five days; or matching placebos. The patients 12 to 19 years of age were randomized in a 2:1 ratio to baloxavir or placebo. Influenza-like illness was defined as the presence of fever 100.4°F (38°C) or higher, at least one respiratory symptom that was moderately severe, and at least one systemic symptom. The median age of patients was 32 to 38 years among the different treatment groups, 77% of the patients were recruited in Japan (the remainder in the United States), and 53% were recruited within 24 hours of the onset of symptoms. Groups were well balanced at randomization. Patients were followed up for 14 days, and the primary outcome was time to symptom alleviation, which was defined as all symptoms being absent or mild for at least 21.5 hours. Of the 1,436 patients who were randomized, 1,064 had influenza confirmed by polymerase chain reaction. In the intention-to-treat population (patients with influenza-like illness), the median time to symptom alleviation was 88.6 hours for placebo and 65.4 hours for baloxavir (median difference = 23.2 hours; 95% CI, 14.0 to 34.2 hours). When limiting the analysis to only those who later were determined by polymerase chain reaction to have influenza, the median duration of symptoms was 80.2 hours for placebo, 53.7 hours for baloxavir, and 53.8 hours for oseltamivir. The benefit was much greater among patients recruited within 24 hours of onset of symptoms than in those recruited between 24 and 48 hours (32.8 hours vs. 13.2 hours; P = .008). Nausea and vomiting were more common with oseltamivir (4.8%), diarrhea was more common with baloxavir (1.8%), but overall the drugs were well tolerated. The number needed to treat to prevent an adverse drug reaction with baloxavir compared with oseltamivir was 25.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Uncertain

Setting: Outpatient (any)

Reference: Hayden FG, Sugaya N, Hirotsu N, et al.; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913–923.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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