New data question oseltamivir’s influenza efficacy, safety

This publication of the most recent iteration of Cochrane reviews on the benefits and harms of oseltamivir and zanamivir marks the first time that reviews of these products included information from all the pertinent clinical trials conducted by the manufacturers. With these comprehensive new reviews based on all the data, the perspective on these drugs has changed substantially. With all the evidence available from treatment and prophylaxis studies it has become clear that convincing trial evidence of a reduction in the risk of hospitalization or complications is lacking.

In addition, the reviews found that oseltamivir causes nausea and vomiting, and probably causes heachaches, renal problems, and psychiatric syndromes. Zanamivir had fewer adverse effects but also had no demonstrated effect on complications or hospitalizations. Zanamivir reduced the duration of symptoms by about half a day, but the reviewers found that it may be no better than other symptom-relief medications. For prophylaxis, zanamivir significantly reduced the risk of symptomatic influenza, but there was heterogeneity among the studies and sample sizes were small. In addition there was no difference in asymptomatic influenza.

Based on these findings it is difficult to conceive that many patients would actively seek these treatments. The benefits involve a shortening of symptoms that few patients would find worth the risk of incurring the harms of treatment. From a health-system perspective, enormous expenditures on these drugs do not appear to have commensurate benefit.

Despite questions raised several years ago about full transparency on the risks and benefits of these two drugs, the medical establishment embraced them. Governments stockpiled the drugs, presuming that their potential public-health benefit merited a substantial financial investment. During this period, when not all of the trial results were fully and widely available, the Centers for Disease Control and Prevention, the U.K. National Institute for Health Care Excellence, the American Academy of Pediatrics, and the World Health Organization all suggested that oseltamivir and zanamivir provided benefits with minimal risks.

Of primary importance for decision makers is that now, with all of the data available for others to evaluate, the knowns and unknowns can be laid out clearly and reveal the weakness of the evidentiary support for these products and what we need to learn about them in the future.

Dr. Harlan M. Krumholz is a cardiologist and professor of medicine and director of the Center for Outcomes Research and Evaluation at Yale University, New Haven, Conn. He said that he has received research grants from Medtronic and Johnson & Johnson and that he chairs a scientific advisory board for UnitedHealthcare. He made these comments in an editorial (BMJ 2014;348:g2548 doi:10.1136/bmj.g2548).