Tamiflu® (oseltamivir) is used to treat influenza virus, the virus that causes the "flu." Tamiflu® is recommended by the CDC in almost all patients
who present within 48 hours of symptom onset. Tamiflu® is also listed as an "essential drug" by the World Health Organization.
Many of the trials involving Tamiflu® were never published. Four years ago, the Cochrane Collaboration requested all the study data pertaining to Tamiflu® from Roche®,
the drug's manufacturer. Roche® balked, and over the next four years, a battle ensued that involved the British Medical Journal
, Roche®, and the European Medicines
Agency (the European version of the FDA). Finally, in 2013, Roche® agreed to release the data to the Cochrane Collaboration. The Cochrane Collaboration performed a meta-analysis
on the data, and the results are presented below.
- PubMed abstract]
- The meta-analysis included randomized, placebo-controlled trials of Tamiflu® used for the treatment, prophylaxis, and post-exposure prophylaxis of influenza
- Trials in both children and adults were evaluated as were trials involving patients with chronic illnesses (e.g. asthma, diabetes, etc.). Immunocompromised patients were excluded.
- Primary outcomes for treatment studies - symptom relief, admission to hospital, complications, and harms
- Primary outcomes for prophylaxis studies - influenza (symptomatic and asymptomatic, always with laboratory confirmation) and influenza-like illness, admission to hospital,
complications, interruption of transmission (in its two components, reduction of viral spread from index cases and prevention of onset of influenza in contacts), and harms
- Of the 83 available trials, 23 trials met the inclusion criteria
- Treatment studies (adults):
- Tamiflu decreased the time to first alleviation of influenza-like illness symptoms in adults by an average of 16.76 hours (95%CI 8.42 to 25.1)
- Tamiflu increased the incidence of nausea (NNH 28) and vomiting (NNH 22)
- Tamiflu decreased the incidence of diarrhea (NNT 43)
- Tamiflu decreased the incidence of "investigator mediated unverified pneumonia" by 1% (NNT 100). When a more strict definition of pneumonia was used, there was no
- Tamiflu had no significant effect on rates of hospital admission
- Prophylaxis studies (adults):
- Tamiflu decreased the incidence of symptomatic influenza (NNT 33)
- Tamiflu had no significant effect on the incidence of asymptomatic influenza (HR 0.78, 95%CI 0.49 to 1.24)
- Tamiflu had no significant effect on admission to hospital (HR 1.14, 95%CI 0.66 to 1.94)
- Tamiflu increased the incidence of headache (NNH 32), nausea (NNH 25), and psychiatric symptoms (NNH 94)
- Treatment studies (children):
- Tamiflu had no significant effect on the time to first alleviation of influenza-like illness symptoms in children (95%CI decrease of 33 hours to increase of 17 hours)
- Tamiflu had no significant effect on rates of hospital admission (HR 1.92, 95%CI 0.7 to 5.23)
- Tamiflu had no significant effect on the incidence of bronchitis (HR 0.65, 95%CI 0.27 to 1.55), otitis media (HR 0.8, 95%CI 0.62 to 1.02), or pneumonia (HR 1.06, 95%CI 0.62 to 1.83)
- Tamiflu increased the incidence of vomiting (NNH 19)
This long-awaited meta-analysis calls into question the benefits of Tamiflu. Tamiflu appears to decrease the symptoms
of flu in adults by about 17 hours at the cost of increased nausea and vomiting. Tamiflu had no obvious benefit in children. When it comes to clinically important outcomes like pneumonia and
hospitalization, Tamiflu showed no proven benefit in any group.
The CDC released a statement after the BMJ meta-analysis was published in which they stood by their previous recommendation that almost all patients receive Tamiflu if treated within 48 hours of symptom
onset (see CDC statement
). In their discussion, they cite evidence from observational studies
to support their position on Tamiflu.
Based on the available evidence, Tamiflu has no proven significant effect on clinically important outcomes. Widespread outpatient use is not supported. Whether Tamiflu improves outcomes in
sicker, hospitalized patients is unclear.