Analgesics Killing More Than Pain, Experts Fear

When All-America defensive back Kenny Easley left UCLA in 1981, he was embarking on an athlete’s dream future. In 1984-85 he led the National Football League in pass interceptions for the Seattle Seahawks and was a unanimous Pro Bowl pick. By the next season his salary had more than tripled, to a reported $650,000 a year.

Then he hurt his ankle. But it wasn’t this injury that at the end of the 1988 season permanently sidelined Easley, who had been regarded as one of the best football players of his generation.

It was his kidneys, destroyed, he says, by the same over-the-counter medication on which Americans spend $500 million every year.

The drug was ibuprofen, which the U.S. Food and Drug Administration released for non-prescription sales in 1984. Its brand names include Advil, Nuprin and Motrin. In pain because of his ankle injury and subsequent physical therapy, Easley took about 20 of the 200-milligram ibuprofen pills daily for five months.

As the FDA considers expanding the number of such drugs available over the counter, some doctors are worrying that this would add to a problem that has gone largely unrecognized in the United States--kidney damage from long-term use of over-the-counter painkillers.

Chief among those have been ibuprofen and the aspirin-substitute acetaminophen, sold under brand names such as Tylenol and Anacin-3.

Furthermore, the incidence of kidney problems caused by analgesics could rise if the increasing number of Americans without medical insurance inappropriately substitute a trip to the drugstore for a visit to the doctor.

There is more evidence of kidney failure related to analgesic use in other countries than there is in the United States, but that is because the American medical system hasn’t bothered to look, believes Dr. William M. Bennett, head of nephrology at Oregon Health Sciences University.

Bennett was on a National Kidney Foundation panel that unsuccessfully urged the FDA to specifically address the potential for kidney problems in its ibuprofen labeling requirements.

“Many people don’t realize that medications taken over the counter are in fact medications, so that physicians don’t ask about them and patients don’t volunteer about them--because they don’t consider them medications,” Bennett said.

Responsible for Many Cases

Bennett estimates that over-the-counter painkillers are responsible for as many as 20% of the 125,000 cases of end-stage kidney disease in the United States. In Australia, the rate is 13%; in West Germany it is 16.5%.

Even if the percentage in the United States is only half as high as Bennett estimates, that would mean the federal government is paying $280 million a year for dialysis, transplants and medical care in patients whose kidney disease was caused by analgesics, according to figures kept by the Health Care Financing Administration. The total federal bill was $2.8 billion in 1987.

Drug companies say they doubt that analgesics are a major cause of kidney disease in the United States. They emphasize that there is virtually no problem if they are taken as directed, that is, for only a few days or under a doctor’s supervision.

“Our studies, good studies, show that most of the time most people know what a medication should be used for, know how to use it, and use it that way,” said John T. Walden, senior vice president of the Nonprescription Drug Manufacturers Assn. “If people use those products as the labeling advises, they will, according to both FDA and industry data, be safe.”

Study Cites Overuse

Bennett agrees--but nevertheless points to a federal study published in May that found that people do overuse acetaminophen.

The study concluded that the risk of serious kidney disease tripled in people who took two tablets of acetaminophen daily for a year. A similar study of ibuprofen is being readied for publication, said Dale P. Sandler, chief author of both studies.

For the consumer, the challenge is to navigate this quagmire of medical nuance without endangering one’s health.

“The watchword is just common sense,” Bennett said. “If you find yourself having a medical problem that requires a daily analgesic you ought to be under the care of a doctor, because it isn’t normal to take analgesics every day.”

How Pills Become Crutch

The typical analgesic overuser is a woman who is heavily stressed by her job, family responsibilities and money or marriage woes, Bennett said. She has headaches, she has backaches--she hurts. A couple of pills become her daily crutch, especially if they contain a bonus boost from caffeine, as some analgesic preparations still do.

Caffeine not only reinforces taking the pills, but there is evidence that acetaminophen taken in combination with caffeine or aspirin is even more toxic to kidneys.

It’s easy for an American to get into a pattern of popping painkillers every day, said F. James Grogan, associate professor of clinical pharmacy at St. Louis College of Pharmacy.

“People suffer from two general misconceptions,” Grogan said. “One is that these drugs must not do very much or they wouldn’t be available over the counter. Secondly, they must not have any side effects or you couldn’t buy them over the counter. And neither of those are true.”

Warnings Easy to Ignore

Over-the-counter drug labels are not required to be specific about side effects, and generalized warnings to see a doctor if symptoms persist are easy to ignore, he said. Advertising also plays a role.

“Mass-media advertising is so pervasive that people don’t really stop to think about what they’re doing,” Grogan said. “I’ve seen very intelligent, well-educated people who have chosen products that are completely inappropriate just because of the advertising.”

The insidious thing about analgesics, Bennett said, is that their negative effects appear to be felt by the kidneys cumulatively but often without any overt symptoms. If caught early, the damage is generally reversible. When symptoms occur, they can be nonspecific signs such as malaise, weight loss, anemia, recurrent urinary infections, high blood pressure and edema.

Just two “extra-strength” 500-milligram tablets of acetaminophen daily, for a total of one gram, would add up in about three years to what appears to be the threshold toxic dose, a kilogram, Bennett noted.

Testing Recommended

Even under a doctor’s care, people who take daily doses of any analgesic for arthritis or for other reasons should have their kidney function tested every six to 12 months, Bennett recommends.

Two processes appear to be at fault in analgesics’ effects on the kidney’s intricate structures for filtering waste products out of the blood.

Nonsteroidal anti-inflammatory drugs, such as ibuprofen, appear to cut down on renal circulation by interfering with the body’s production of prostaglandins, substances that regulate blood flow in the kidney. Lower blood flow can mean cell death.

“If you’ve already got underlying heart disease and your circulation is poor through the kidney, and then you take something else that makes it poorer, then you can get into trouble,” Sandler said.

However, Sandler’s study found no evidence that the most commonly used nonsteroidal anti-inflammatory drug, aspirin, resulted in kidney damage.

A Different Process

Acetaminophen seems to cause kidney damage through a second process, by building up concentrations in the kidney that directly result in cell death. An acetaminophen relative that was banned in the U.S. in 1983, phenacetin, appears to act similarly. (Phenacetin was the “P” in APCs. The other ingredients were aspirin and caffeine.)

The FDA has no plans for action on the acetaminophen issue, said Bill Grigg, director of press relations for the agency. The only reports to FDA of kidney damage associated with the drug have occurred in people who also were taking other drugs that could have been to blame, he said.

Neither is the FDA considering extra warnings on ibuprofen, Grigg said.

Bennett suggests that a multimillion-dollar verdict for Kenny Easley could provide the impetus for drug companies as well as the FDA to take more seriously the possibility that uninformed consumers will take too many painkillers for too long.

In April, Easley sued the Seahawks, the team doctors and the ibuprofen manufacturer, Whitehall Laboratories, for unspecified damages in Seattle. The case is expected to come to trial within two years.

Meanwhile, Easley marks his time not by the NFL schedule, but by his encounters with the dialysis machine that, three times a week, cleans his blood and keeps him alive.