Postmarketing Safety of Sildenafil Citrate (Viagra)

Summary of Reports of Death in Viagra Users Received from Marketing (late March) through mid-November 1998

In response to Freedom of Information requests, the FDA is posting a summary of reports of death in sildenafil citrate (Viagra) users. This posting does not suggest a change in FDA's perspective concerning the safety of Viagra. The intent is simply to provide easier access for those who have requested this information.

The limitations of spontaneous postmarketing adverse drug event data should be considered when interpreting these data:

Reports are submitted voluntarily, and the magnitude of underreporting is unknown. Some of the factors that may influence whether an event is reported include: awareness by health professionals and consumers of adverse drug event reporting, seriousness of the reaction, market share of the drug, length of time since marketing, publicity about a drug or an adverse event, litigation, and regulatory actions.

Because of underreporting and uncertainty concerning the number of persons exposed to a drug, it is not possible to calculate a true incidence rate of a particular event for a specified drug.

In some reports, clinical information (such as medical history, validation of diagnosis, time from drug use to onset of illness, dose, and use of concomitant drugs) is missing or incomplete. Follow-up information may not be available.

An accumulation of adverse event reports does not necessarily indicate that the adverse event was caused by the drug; rather, the event may be due to an underlying disease or some other factor(s).

The reports summarized below have been reviewed to eliminate duplicates. Numbers of reports from a computerized listing of the Adverse Event Reporting System (AERS) should therefore not be expected to match the numbers below, as those listings also contain duplicate reports and reports that are little more than hearsay.

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FDA/Center for Drug Evaluation and Research

From the marketing of sildenafil citrate (Viagra) in late March through mid-November 1998, during which more than 6 million outpatient prescriptions (representing about 50 million tablets) were dispensed, the FDA received reports of 130 U.S. patients who died after having been prescribed this drug. Excluded were reports of 55 foreign patients, 35 with unverifiable information (from hearsay, rumor, the media, or unidentifiable reporters), and 22 with unconfirmed Viagra use.

Of the 130 U.S. patients, two men died from homicide and drowning; three had strokes; and 77 had cardiovascular events (41 with definite or suspected myocardial infarction, 27 with cardiac arrest, 6 with cardiac symptoms, and 3 with coronary artery disease). Cause of death was unmentioned or unknown for 48. All with gender specified were men. Age was provided for 104 individuals whose average age was 64 years (median = 64, range = 29-87). Of 62 with Viagra dose reported, 3 had taken 25 mg; 46, 50 mg; 9, 100 mg; 2, 50-100 mg.; 1, more than 100 mg (exact dose unknown); and 1, an overdose. Sixteen men took or were administered nitroglycerin or a nitrate medication that is contraindicated with the use of Viagra. In addition, three men were found with nitroglycerin in their possession, but it is not known if it was taken.

Time from use of Viagra to death or onset of symptoms leading to death was examined since the drug is taken periodically and since a direct effect of the drug would be limited to a finite period after drug ingestion. Excluding the two men who died from homicide and drowning, 44 (34%) of the 128 patients died or had onset of symptoms leading to death within 4 to 5 hours of Viagra use (including 27 during or immediately after sexual intercourse). Six died or developed symptoms later the same day; 8, the next day; 5, two days later; and 4, three to seven days after Viagra use. The time from drug ingestion to death or onset of symptoms leading to death was not stated or was unknown for 61 men (48%).

Ninety (70%) of the 128 patients had one or more risk factors reported for cardiovascular or cerebrovascular disease (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity, previous cardiac history). Three additional persons without identified heart disease or risk factors had severe coronary artery disease detected at autopsy. Twelve were reported to have no previous history of cardiac disease or risk factors, but for 10 of these, the time from last Viagra use to death or onset of symptoms leading to death was unknown or was at least two days later. Two men, 60 and 70 years old, had no mentioned risk factors, no sexual activity, and died shortly after Viagra ingestion.

Consideration has been given to the following factors in assessing the relevance of these reports: the high background rate of sudden cardiac death in men in the United States; the large prevalence of risk factors for sudden cardiac death in Viagra users who have died; the additional risk associated with sexual activity; the number of deaths in relation to the amount of drug use; underreporting of adverse events; the quality of reports received; temporal relationship between the drug and the adverse event; the possible biological plausibility between the drug and the adverse event; and others.

Based on these reports and other information, the manufacturer, in consultation with the FDA, has revised the product label (see http://www.fda.gov/cder/foi/nda/98/viagra/viagralabel.pdf).

As with all approved medications, the FDA will continue to monitor the postmarketing safety of Viagra by carefully reviewing reports of death and other serious adverse events and will continue to evaluate the need for regulatory action.

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Last Updated: March 08, 2001