People who consume two or more tablets of acetaminophen--the primary ingredient in Tylenol and other popular painkillers--on a daily basis for at least a year have triple the normal risk of developing disabling kidney disease, according to a new study reported today.
And, use of such painkillers may cause as much as 20% of all kidney disease requiring dialysis or transplants, according to a second article, also in the New England Journal of Medicine. An estimated 100,000 Americans have suffered complete kidney failure and currently receive such therapy.
But a spokesman for Johnson & Johnson Co., the manufacturer of Tylenol, which dominates the market, attacked the study on the acetaminophen hazard as poorly designed. Acetaminophen "has established a remarkable record of safety . . . and continues to be the safest medicine available for effective relief of the aches and pains encountered by the general population," company spokesman Robert Andrews said.
The study's primary author, epidemiologist Dale P. Sanders of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., agreed with Andrews that acetaminophen is not a hazard when used infrequently. Her study, she said, "does not demonstrate any (adverse) effect for acetaminophen when taken as directed, which is when needed for symptoms."
The study poses a possible dilemma for millions of people who require frequent pain relief and have switched from aspirin to acetaminophen because it was thought to be safer. Acetaminophen is much less likely than aspirin to cause significant side effects or allergic problems, and it does not irritate the stomach or cause bleeding.
According to the National Headache Foundation, as many as 45 million Americans suffer chronic headaches and may use painkillers frequently. Nearly 32 million suffer arthritis severe enough to require medical care, and most of these also use painkillers.
Acetaminophen is the primary ingredient of Tylenol, Anacin-3, Panadol and Datril, which are used on a regular basis for relieving the pain of arthritis, chronic headaches and other illnesses. It accounts for about 37% of the nation's $2.5-billion-per-year market for over-the-counter painkillers, according to the consulting firm Kline & Co. Aspirin represents about 43% of the market and ibuprofen 20%.
Acetaminophen's share of the market has been growing at the expense of aspirin since the 1970s, largely because of the safety issue.
About the only previous blemish mark against it was a 1986 report that it can cause serious liver damage in alcoholics. But some previous anecdotal evidence, according to Dr. William M. Bennett of the Oregon Health Sciences University in Portland, had suggested that heavy acetaminophen use might cause kidney problems in non-alcoholics.
Although the primary causes of kidney failure are glomerular nephritis (kidney inflammation), diabetes and hypertension, Sandler said in a telephone interview that the cause of at least 25% of the cases is unknown.
Because the kidney is involved in clearing potentially toxic materials from the body, she and her colleagues guessed that chemicals--including drugs--might cause these unexplained cases.
The group studied 554 patients who had recently been admitted to four North Carolina medical centers with serious kidney disease. In hourlong telephone interviews, they questioned the patients or their family members about their medical histories, their past use of painkillers and other drugs and their exposure to industrial chemicals.
Their answers were then compared to those obtained in the same manner from 516 healthy individuals.
The researchers found that individuals who admitted consuming at least two acetaminophen tablets per day for at least a year were 3.21 times as likely to develop severe kidney disease as those who did not use painkillers. Those who used a similar quantity of phenacetin, which was removed from the U.S. market in 1983, were 5.11 times as likely to develop kidney disease. The researchers found no significant increased risk for aspirin.
Bennett and Dr. Marc E. DeBroe of the University of Antwerp in Belgium noted in an editorial in the same issue of the Journal that researchers at the Free University of Berlin in West Germany are preparing to publish a similar study with similar results.
Johnson & Johnson's Andrews particularly attacked the group's use of family interviews to obtain information about use of painkillers, saying their use was "unacceptable" because it is not reliable. Sandler noted, however, that their methods had received extensive review before being approved for publication and that identical results were obtained if they used only the answers given by patients themselves or only the answers given by proxies.
"People are sick and they die," she said. "You have to ask somebody."