Tamiflu Shortage: So What?
Evidence released by the manufacturers of Tamiflu and Relenza has raised questions concerning the drugs' efficacy and safety.
Questions concerning strategies to deal with the oseltamivir (Tamiflu) shortage are abundant these days. While the pharmacy community is fixed on ensuring adequate supply to meet the increasing demand during influenza season, more serious questions are being asked.
Concerns about the actual effectiveness of the drug in shortening influenza symptoms, reducing complications, and limiting the spread of the flu in pandemic situations are being raised based on new data that Roche and GlaxoSmithKline (GSK) have made available to researchers.
In April 2014, the BMJ published 2 systematic reviews of newly released regulatory information containing previously withheld patient data from Roche, the manufacturer of Tamiflu, and GSK, the manufacturer of zanamivir (Relenza), conducted by the Cochrane Acute Respiratory Infections Group.1,2 This new review included data that had not been made publicly available at the time when the US government had stockpiled $1.3 billion worth of Tamiflu.
While the results of the study have been discussed in detail by evidence-based medicine experts on medical education outlets, including the Academic Life In Emergency Medicine blog and the Skeptics Guide to Emergency Medicine podcast, this new data suggests that oseltamivir shortens the duration of influenza symptoms by a mean of 16.8 hours, but there is no significant reduction in hospital admissions, confirmed pneumonia or other complications, and transmission of influenza among patients who received the drug prophylactically.1
Furthermore, despite the limited reduction in duration of influzena, those who received oseltamivir were more likely to experience nausea, vomiting, psychiatric events, and headache. Headache, in particular, was demonstrated to occur in a dose-escalating fashion, raising concerns for further neuropsychiatric complications in patients receiving a high dose (150 mg) or those with renal impairment.1 Similarly, results regarding the safety and effectiveness of zanamivir were strikingly similar: reduction in duration of influenza symptoms by 14.4 hours, but no reduction in confirmed pneumonia and other complications.2
The results of this trial were met with a quick response from Roche, stating that it disagreed with the findings, questioned the methodology of this review, and stood behind the public health benefits of oseltamivir.3 When examining the totality of evidence and the previous experience of such evidence being withheld from the public, however, it is hard to put together why the evidence analyzed by a trusted group should be disregarded and yet another $1.3 billion be spent restocking the nation once the current supply of oseltamivir expires in the near future.4
- Heneghan CJ, Onakpoya I, Thopson M, Spencer EA, Jones M, Jefferson T. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348: g2547.
- Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348: g2545.
- Abbasi K. The missing data that cost $20bn. BMJ. 2014;348:g2695.
- Torjesen I. Cochrane review questions effectiveness of neuraminidase inhibitors. BMJ. 2014;348:g2675.
- Krumholz HM, Hines HH. Neuraminidase inhibitors for influenza: The whole truth and nothing but the truth. BMJ. 2014; 348: g2548.