Oseltamivir (Tamiflu) reduces duration of influenza symptoms, respiratory complications, and hospital admissions

1. A meta-analysis of oseltamivir (Tamiflu) treatment for influenza found that oseltamivir significantly reduced the time to relief of influenza symptoms by approximately one day in those infected with influenza compared to placebo.

2. Oseltamivir treatment resulted in fewer respiratory tract infections requiring antibiotics and fewer hospital admissions for any causes, but increased the risk of nausea and vomiting, compared to placebo.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Neuraminidase inhibitors, such as zanamivir and oseltamivir are used to treat and prevent influenza virus infection, and oseltamivir especially, has been widely used to treat recent influenza pandemics. However, there have been questions regarding the efficacy of oseltamivir as well as the adverse effect profile. This study conducted an individual patient data meta-analysis of all available randomized clinical trials using oseltamivir vs. placebo to treat influenza in adults, analyzing intention-to-treat infected (those with influenza infections), intention-to-treat (all treated participants), and safety populations.

Oseltamivir treatment significantly reduced the duration of influenza symptoms by 21%, or 25.2 hours in those with confirmed influenza compared to placebo, as well as by 15%, or 17.8 hours, in the entire study population, and did not reduce symptom duration in participants without influenza infection. Additionally, oseltamivir treatment resulted in fewer lower respiratory tract complications requiring antibiotics and fewer hospital admissions, but also increased the risks of nausea and vomiting compared to placebo. Strengths of this study included conducting a meta-analysis of individual patient data and using intention-to-treat infected populations of participants. Limitations included not pre-defining respiratory complications or that the percentage of infected participants in the study may not be generalizable to actual real-world infection percentages.

Click to read the study in The Lancet

Relevant Reading: Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

In-Depth [meta-analysis]: This study included all published and unpublished randomized placebo-controlled, double-blind clinical trials using oseltamivir for treatment of influenza in adults, comprising 4,328 participants from nine trials between 1997 and 2001. The intention-to-treat population included 2,402 participants randomly assigned to receive 75mg oseltamivir twice daily for five days or 1,926 to placebo with a 21 day follow-up. The intention-to-treat infected population, defined as those with confirmed influenza infections, included 1,591 (66%) of the oseltamivir group and 1,203 (68%) of the placebo group. The safety population included 2,401 participants receiving oseltamivir and 1,917 receiving placebo. Eligibility criteria included feeling unwell within 36 hours, fever, and at least two influenza symptoms including one respiratory and one constitutional symptom. The primary outcome was time to relief of seven influenza symptoms (nasal congestion, sore throat, cough, body aches, fatigue, headache, chills) for at least 21.5 hours.

In the influenza-infected population, oseltamivir significantly reduced the time to relief of influenza symptoms by 21% with oseltamivir vs. placebo (time ratio 0.79, 95% Confidence Interval [CI] 0.74-0.85; p<0.0001), or a difference of 25.2 hours, with a similar reduction of 15% in the intention-to-treat population (time ratio 0.85, 95% CI 0.80-0.90; p<0.0001), or a difference of -17.8 hours. In the infected population, the oseltamivir group had a 44% reduction in risk of lower respiratory tract complications requiring antibiotics vs. placebo (risk ratio [RR] 0.56, 95% CI 0.42-0.75; p=0.001) and fewer hospital admissions for any causes (RR 0.37, 95% CI 0.17-0.81; p=0.13). However, oseltamivir also increased the risks of nausea (RR 1.60, 95% CI 1.29-1.99; p<0.0001) and vomiting (RR 2.43, 95% CI 1.83-3.23; p<0.0001).

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