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Oseltamivir Won’t Keep You Out of the Hospital 

February 26, 2024

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Written by Jason Lesnick

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This systematic review and meta-analysis concluded, with moderate certainty evidence, that oseltamivir has little to no effect on hospitalization but does increase nausea and vomiting. 

No drug for you!
This systematic review and meta-analysis included 15 studies that were RCTs comparing oseltamivir against placebo or standard care in outpatients ≥ 12 years with confirmed influenza. Kudos to the authors for finding 8 unpublished clinical study reports to include in the final meta-analysis. 

They examined differences in hospitalization by estimating risk ratio (RR) and risk difference (RD). The GRADE framework was used to evaluate the certainty of evidence. The authors also performed several pre-specified secondary analyses including mean population age, method of confirming influenza, high vs low risk population, and trial sponsor. 

6,166 individuals made up the intention-to-treat-infected (ITTi) population, and 53.9% were prescribed oseltamivir. Average age was 45.3 years, 53.6% of patients were female. 9 of the 15 included trials were sponsored by Roche, and across all studies the rate of hospitalization was low at 0.8%. 

Oseltamivir was not associated with decreased risk of hospitalization in the ITTi population: RR 0.79 (95%CI 0.48 to 1.29); RD -0.17% (95%CI -0.23% to 0.48%). Treatment with oseltamivir was not associated with decreased hospitalization in older populations: mean age ≥ 65 years: RR 1.01 (95%CI 0.21 to 4.90); nor was it in patients at greater risk of hospitalization: RR 0.65 (95%CI 0.33 to 1.28). In all randomized patients who received at least 1 treatment dose, there was increased nausea: RR 1.43 (95%CI 1.13 to 1.82) and vomiting RR 1.83 (95%CI 1.28 to 2.63) but not serious adverse events: RR 0.71 (95%CI 0.46 to 1.08). 

There was a subgroup analysis that showed when limited to industry-sponsored studies, there was a suggested decreased risk of hospitalization in the ITTi population. Some differences that could explain these findings are that these studies confirmed influenza infection differently (with viral culture or a 4x rise in antibody response rather than PCR) and a lower resistance to oseltamivir when these studies were performed. 

How will this change my practice?
Based on this study, my shared decision making discussion regarding prescribing oseltamivir for influenza patients stable for outpatient management will evolve to include that there is no evidence oseltamivir decreases hospitalization. I will continue to mention increased GI side effects and the possibility of 1725 hours fewer symptoms. In my experience, some patients still want to stomach the increased cost and risk of side effects for that potential improvement.

Editor’s note: Oseltamivir is recommended in the 2018 IDSA guidelines for hospitalized patients, outpatients with progression of disease, those with chronic medical conditions or immunocompromise, those <2 or ≥65 years old, and pregnant women (or 2 weeks postpartum) – regardless of duration of symptoms. In others, use shared decision making. ~Clay Smith

Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza. JAMA Intern Med. 2024 Jan 1;184(1):18-27. doi: 10.1001/jamainternmed.2023.0699. Erratum in: JAMA Intern Med. 2023 Nov 20;: PMID: 37306992; PMCID: PMC10262060.

What are your thoughts?