Important New Warnings about the Flu Drug Zanamivir (RELENZA)
Health care professionals were notified in July 2000 about important revisions in the safety labeling for the flu drug zanamivir (RELENZA). The warning concerned serious respiratory adverse events. Zanamivir is manufactured by Glaxo Wellcome Inc.
Since zanamivir’s approval in July 1999, the professional product labeling, or “package insert,” has included a precaution describing the drug’s potential for causing bronchospasm in patients with underlying respiratory disease such as asthma or chronic obstructive pulmonary disease (COPD), and has stated that the safety and efficacy of the drug have not been demonstrated in this population of patients. The precaution goes on to state that zanamivir should be stopped in any patient who develops bronchospasm or a decline in lung function. The labeling also warns that in such patients, zanamivir should be used under conditions of careful monitoring, proper observation and appropriate supportive care, including the availability of short-acting bronchodilators, for example a “puffer” containing albuterol (PROVENTIL).
The new warnings are the result of additional reports of serious respiratory adverse events when zanamivir was used in patients with known airways disease. Reports have also been received of a decline in respiratory function in patients without a history of airways disease. Some adverse events have required immediate treatment or hospitalization, and some patients have died.
In the November 1999 issue of Worst Pills, Best Pills News, we listed zanamivir as Do Not Use because of its lack of effectiveness. We based this recommendation on questions raised during the Food and Drug Administration’s (FDA) Antiviral Drug Advisory Committee’s hearings that reviewed zanamivir and its 13-4 vote not to recommend the drug’s approval on the ground that it did not work. After we had the opportunity to examine the FDA’s full assessment of zanamivir, we presented the agency’s statistical review of the drug in the February 2000 issue of the newsletter.
The FDA statistical reviewer concluded his evaluation by saying, “Zanamivir has not been shown to be effective in this country for the treatment of influenza, and in my opinion therefore should not be approved.” We agreed and concluded, “Unfortunately, the ‘new’ FDA management sees its role as the industry’s partner in developing new drugs rather than ensuring that only safe and effective drugs are cleared for marketing.”
The safety and effectiveness of a new drug are closely linked. Whenever the effectiveness of a new drug is marginal or non-existent, as is the case with zanamivir, risk always outweighs benefit no matter how small the risk.
Problems began to arise with zanamivir during the first flu season it was on the market. The FDA issued a public health advisory January 12, 2000, about the safe and appropriate use of flu drugs. Reports had been received of patients with serious bacterial infections who initially had flu-like symptoms and whose bacterial infections progressed during treatment when only flu drugs were prescribed. Doctors were cautioned that patients with severe flu-like illness, especially those with chronic medical conditions or complicated manifestations of acute illness, might have significant bacterial infections instead of, or in addition to, the flu virus. The flu drugs do not work against bacterial infections and appropriate antibiotic treatment should be started if bacterial infection is suspected.
We reviewed zanamivir’s competitor oseltamivir (TAMIFLU) in the January 2000 issue of Worst Pills, Best Pills News and because of its marginal effectiveness listed it as Do Not Use. Oseltamivir is manufactured by Roche Pharmaceuticals.
Roche’s application to market oseltamivir in Europe has hit a roadblock. The British publication SCRIP, that covers the pharmaceutical industry worldwide, reported in late-May 2000 that Roche had withdrawn its application for oseltamivir. Some members of the European regulatory committee felt that the company had not provided sufficient evidence that oseltamivir was effective in the treatment of influenza B.
The Centers for Disease Control and Prevention (CDC) has announced for the upcoming 2000–2001 flu season that there has been lower than expected production of one of the components of this year’s flu vaccine. There have also been other manufacturing problems that are expected to lead to a substantial delay in the distribution of flu vaccine and possibly substantially fewer total doses of vaccine for distribution than last year. Even if a flu vaccine shortage develops, the CDC and the Advisory Committee on Immunization Practices (ACIP) do not support the routine and widespread use of drugs to prevent flu because this is an untested and expensive strategy that could result in large numbers of persons experiencing adverse effects.
What You Can Do
If you have a high fever (greater than 101oF or 38.3oC) accompanied by shaking chills and you are coughing up thick phlegm, or if coughing or breathing deeply causes sharp chest pain, you may have pneumonia, and should consult your doctor for diagnosis and appropriate treatment.