Hey, Who Needs a Prescription?

By Linda Marsa

Sept. 29, 1996 12 AM PT

Linda Marsa's book, "Prescription for Profit", about the pharmaceutical industry, will be published by Scribner in May 1997. Her last article for the magazine was about the drug AZT

Phyllis De Sort almost died. Yet until the moment she passed out on the bathroom floor of her spacious Bel-Air home early one hazy June morning, the former nurse had no inkling that shewas so ill. Throughout the previous week, she’d felt lightheaded and nauseous, with severe stomach cramps. Her husband kept nagging her to go to the doctor, but she was too busy running their TV-commercial production company to take any time off. It’s probably nothing more serious than the flu, she thought. Until she collapsed.

Her husband found her unconscious and rushed her to the UCLA Medical Center’s Emergency Room, where it was swiftly determined that she had a bleeding ulcer. Once her condition was stabilized, she was shipped up to the intensive-care unit, where doctors quickly staunched the bleeding, and a total of three pints of blood were pumped into her tiny 104-pound frame. If she hadn’t made it to the hospital on time, De Sort reflects today, “I might have bled to death.’

What’s especially chilling was the culprit behind De Sort’s almost fatal bout of internal bleeding: ibuprofen, an over-the-counter medication she’d been popping every night to relieve her arthritis. Ibuprofen, the active ingredient in such pain relievers as Advil, Nuprin and Motrin IB, is one of a class of medications known as non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs like ibuprofen, a powerful analgesic that was available only by prescription until 1984, are tiny miracle workers that can ease inflammation and pain. But they have a downside if they’re consumed habitually for prolonged periods: They can wreak havoc on the stomach by eating away at the lining until an ulcer forms, which may then perforate the stomach walls and provoke serious bleeds. Ulcers can be silent, says De Sort, “so I never had the slightest idea that I was bleeding. But I nearly did myself in.’

What happened to Phyllis De Sort is surprisingly common. Doctors have known for years that chronic pain sufferers who take NSAIDs like ibuprofen regularly to ease their symptoms are prone to gastric disorders. “There’s an epidemic of adverse drug reactions to NSAIDs,’ says Dr. James F. Fries, one of the country’s leading arthritis experts and a professor of medicine at Stanford University School of Medicine. “The Food and Drug Administration believes anywhere from 10,000 to 20,000 deaths each year are the result of severe bleeding caused by NSAIDs. It’s a big problem.’

What’s a bigger problem is that ibuprofen is by no means the only potent medication with potentially fatal side effects that is now available without a prescription. More than 600 over-the-counter medications, including Advil and Motrin, allergy and cold medications such as Sudafed, Allerest and Benadryl, sleep aids, anti-itch skin creams and shampoos that eradicate head lice, use ingredients or dosages that could be dispensed only by prescription 20 years ago.

And while prescription drugs have been switched to OTC status for more than 40 years, nothing has ever approached the magnitude of the recent avalanche. In 1995, six drugs were cleared to leave the sanctuary of the pharmacy counter; as of August 1996, seven had switched. “This last year was quite a year for OTC switches, probably the most we’ve approved in one year,’ says Dr. Debra L. Bowen, director of the FDA’s division of OTC products.

In the past three years, three new entrants muscled into the overcrowded pain-reliever market--Aleve, Actron and Orudis KT. Another four--Zantac 75, Tagamet HB, Pepcid AC and Axid AR--joined the already ample OTC heartburn arsenal. New also are creams to treat yeast and fungus infections, others to cure baldness, and several aids to ease smoking withdrawal. And with as many as 20 drugs, such as cholesterol-lowering medications and treatments for genital herpes, awaiting FDA clearance, next year promises to be the biggest switchover year ever.

While the drug firms tout these changes as providing consumers more control over their own health, the deluge has consumer watchdog groups, pharmacists and physicians worried that drugs with potentially dangerous or even life-threatening side effects could be misused by an uneducated public. “The more drugs there are out there for people to use without a prescription, the more you increase the risk of potential problems,’ says Philip Hansten, professor of pharmacy at the University of Washington School of Pharmacy and an expert on drug interactions.

The voices of protest are scattered and reactive; studies on individual OTC drugs are often done after a problem, like bleeding ulcers, has emerged in a significant number of people.

“People assume there are all these vigilant FDA staffers sitting around terminals, analyzing this data on a daily basis--like air-traffic controllers monitoring a radar screen--and whenever they see blips, they instantly spring into action,’ says Joe Graedon, a pharmacologist and co-author of “The People’s Pharmacy,’ a consumer handbook. That simply is not the case. It is virtually impossible to monitor the effects of a drug as ubiquitousas ibuprofen. And the FDA, understaffed and underfunded, has many masters, including a public that wants easy access to potent medications and doesn’t want to sit in a doctor’s waiting room every time a headache or an allergy attack hits. The upshot is, “We’re asking consumers to make increasingly complicated medical decisions without enough information or supervision,’ says Larry D. Sasich, a pharmacist and research analyst with Public Citizen Health Research Group.

“People naively believe that over-the-counter preparations are so harmless they can pop them like candy,’ says Tim R. Covington, a professor of pharmacy at Samford University in Birmingham, Ala., and editor of the American Pharmaceutical Assn.’s “Handbook of Nonprescription Drugs.’ “But they’re not.’

Nearly all OTC versions of prescription drugs are marketed in lower dosages, but that doesn’t keep people from taking enough pills to make up the difference. Also, mixing many OTC drugs with prescription medicines or alcohol can trigger grave adverse reactions. And, Covington maintains, habitual use of such remedies can mask the symptoms of serious underlying disorders, which, if left untreated, could be fatal.

Of course, the $64,000 question is how a drug can one day be taken only with a doctor’s supervision and the next day be sold at the local mini-mart. Clearly, the drug itself, its efficacy and potential hazards do not change. So what does? “There are no specific ‘cookbook’ guidelines for switching products,’ says Randy Juhl, former chair of the FDA’s Nonprescription Drug Advisory Committee.

The process is initiated by the pharmaceutical manufacturers, who typically apply to the FDA to switch a prescription drug that has a proven safety record--though, as Graedon observes, “it is no coincidence that companies apply when a drug is losing patent protection.’

“The thinking is that these products have done very well by prescription,’ says Katherine Armstrong, a spokeswoman for Johnson & Johnson, which brought, among others, Monistat 7 OTC in 1990 and has recently followed with a prescription-strength version, Monistat 3. “In the changing health-care environment, there is a trend toward reducing costs, and OTC availability has been shown to lower costs, putting the power of responsibility onto the patients. Johnson & Johnson is supportive of these trends.’

Not all drugs make it through the FDA’s approval process. Codeine, an addictive painkiller, and acyclovir, an antibiotic to which patients may become resistant, are just two examples of those that didn’t. . “There are certain classes of products which would never be appropriate for OTC use,’ Armstrong says. “Drugs that require either constant blood monitoring or whose actions necessitate a very high level of observation. Then there are other drugs which are used for common, easily treatable illnesses, like yeast and urinary tract infections, that tend to reoccur. [People] recognize the symptoms. We’re not trying to cut out the doctor. We’re very clear on all of our packaging’ to indicate when a patient should contact a doctor.

Experts inside and outside the pharmaceutical industry maintain that when taken as directed, these drugs are effective and safe. And that moving drugs from prescription to OTC status is a vital component of the self-care revolution. “There are tremendous benefits for consumers with increased access,’ says George Quesnelle, director of medical marketing at SmithKline Beecham Consumer Healthcare. “And it also takes the pressure off the health-care delivery system.’

In fact, drug industry trade groups calculate that--when prescription costs, doctor visits, lost time from work, insurance fees and travel are factored into the equation--increased consumer access to powerful OTC drugs will translate into annual cost savings of $34 billion by the year 2000.

Industry analysts aren’t so enthusiastic, however. The OTC stampede is merely a visible symptom, say industry observers such as Dr. Michael B. Nichol, a pharmaceutical economist at USC, of what’s really happening--a seismic shift in the way the pharmaceutical industry has historically done business. “It’s clear,’ says Nichol, “that the managed-care revolution will severely restrain the ability of pharmaceutical companies to make profits off their prescription drugs.’

ONCE UPON A TIME, the pharmaceutical industry was the envy of American business. Companies posted double-digit profits in 1990, for instance, more than triple the average of all Fortune 500 companies. Drug making was hugely profitable because it was the only private industry on this side of the Iron Curtain insulated from the heat of price competition.

Prescription drugs are the only products in the world that aren’t chosen by the people who use them. For decades, doctors called all the shots. “In the old days, the drug company only had to worry about prescribers,’ says David A. Knapp, dean of the School of Pharmacy at the University of Maryland at Baltimore, “and focus on a small sliver of the marketplace.’ So pharmaceutical companies didn’t have to spend millions coming up with catchy ad campaigns, or worrying about packaging, television spots or competitive pricing. All they had to be concerned about were the doctors--a limited market, easily identified and easily reached. And doctors were bombarded by a barrage of information, at company-sponsored seminars and medical conventions, in splashy ads in medical journals and at “educational events’ held, conveniently, in places like Hawaii or Cabo San Lucas, and wooed by the battalion of salespeople deployed to persuade physicians to prescribe their medications. Superior efficacy or cheaper cost had little bearing on a drug’s market success; often the key was the aggressiveness of a company’s sales team.

But in the early 1980s, several factors combined to spoil this free-enterprise paradise. Pharmaceutical-industry money managers, says Knapp, decided that drugs were selling at fire-sale price tags, so they hiked prices. Over the next decade, prescription drug costs rose at nearly three times the inflation rate. Pharmaceutical executives defended the increases, citing high research-and-development costs. And, they argued, drugs were infinitely more cost-effective than other treatments--it’s cheaper to, say, treat a heart attack patient with a $2,200 dose of Activase, Genentech’s clot-busting heart medication, than with $50,000 worth of open-heart surgery. That argument notwithstanding, the price-boosting decision upset the delicately balanced economic equation. “Raising prices may well have been policy miscalculation,’ says Knapp, “because it laid the groundwork for insurers to come in and look at cost-cutting, which they did with a vengeance.’

Suddenly, an entirely new player was in the game: the pharmaceutical benefit managers (PBMs). PBMs acted as brokers between drug companies and the managed-care outfits--HMOs, PPOs and big medical groups that were mushrooming up across the country. Individual doctors were replaced by committees that chose which medications would be stocked in the groups’ pharmacies. “The principles of managed care now effectively dominate the distribution channels for drugs,’ says Sheila Shulman, assistant director of the Tufts Center for the Study of Drug Development.

In any given class of drug--ulcer medications like Zantac, antidepressants such as Prozac--a fleet of “copycat’ products compete for market share. Thus, the PBMs could cherry-pick drugs made by companies willing to bargain and freeze out the others and ensure deep discounts on large volume purchases. “Drug making was the only industry in the world not responsive to the market forces of capitalism,’ Knapp says. “Managed care changed all that. Suddenly, price counted.’ And pharmaceutical companies found themselves struggling to make a profit from prescription drugs.

At the same time, blockbuster drugs worth an estimated $13.5 billion a year in sales were going off patent, ending their lucrative monopolies. Drugs like Zantac, Prozac, Zovirax and Seldane were scheduled to lose patent protection by the turn of the century, opening up the floodgates of competition from cheaper generic versions. And few innovative therapeutics had emerged from the lab to replace them--research was directed primarily at concocting “me too’ drugs. According to a 1989 report from the Senate Subcommittee on Aging, between 1981 and 1988, pharmaceutical companies introduced 348 drugs. Yet, only 12--less than 3%--were considered important therapeutic advances by the FDA.

With a paucity of promising drugs under development and profits being seriously eroded by the managed-care revolution and the loss of patent protection, the industry was in crisis. “The lifeblood of research-intensive pharmaceutical companies is developing new chemical entities,’ Knapp says. “But more and more companies find they don’t have the resources to bring out a new product. Therefore, in the last five or so years, there’s been tremendous pressure to find other ways to make money.’ So in the mid-’80s, drug companies began to bypass traditional promotional channels and advertise prescription medications directly to the public. This increased brand-name awareness, inducing patients to ask for the drug by name, thus circumvented the restrictions imposed by some managed-care groups on which drugs could be prescribed. The industry now spends more than $300 million a year--up from $35 million in 1987--to persuade TV viewers and magazine readers to “ask their doctor’ about medicines such as Claritin, a prescription antihistamine; Premarin, an estrogen supplement for post-menopausal women, or the hypertensive drug, Cardizem CD.

But the logical strategy for beefing up anemic bottom lines was to switch blockbusters going off patent to OTC status. That approach eliminates the need to see doctors and expands potential outlets by many orders of magnitude--from 55,000 pharmacies to more than 750,000 retail locations across the country. “Fear of lost profitability has created a tremendous interest in switching,’ says Graedon.

And switching can be very, very good business. Benadryl, for example, notched sales of $20 million in 1985, the year before it went OTC. Within a decade, its sales swelled past $140 million. Switching meant that, virtually overnight, remedies for, say, vaginal yeast infections, which previously had to be closely monitored by a woman’s doctor, became as convenient to buy as a carton of milk.

And companies concocted clever marketing campaigns to capitalize on the aura of scientific respectability endowed by a drug’s former prescription status. The television spots that marked the splashy debut of the OTC version of the stomach-acid blocker Tagamet, for instance, used images that implicitly positioned the product right on the cutting edge of space-age technology--a blinding eclipse of the sun accompanied by a sonic boom with the tag line: “The idea behind it led to the Nobel Prize for Medicine.’

Little wonder that switched drugs like Tagamet HB quickly shoot past long-established rivals to become leaders in their product categories. In 1994, according to Kline & Co., 10 of the 20 top-selling OTCs were products once available only by prescription. Thanks to all the new entrants in the OTC market, industry analysts estimate that, by the year 2000, OTC switches should ring up $20 billion in sales, up from $4.4 billion in 1993. That certainly would be welcome relief for beleaguered drug companies.

“Health insurance companies love it, too,’ adds Ruth Smarinsky, a pharmacist at the Venice Family Clinic, “because once a prescription drug is OTC, they don’t have to pay for it.’

Everyone is happy, except, perhaps, the consumer.

ANTONIO BENEDI IS a drug company’s worst nightmare: a plaintiff with a virtually airtight medical product liability case. He’s so clean he squeaks. “I can’t remember the last time I got a parking ticket,’ says Benedi, who was an aide to President George Bush for 12 years. He lived with his wife, a preschool teacher, and their two young sons in a comfortable suburb outside the nation’s capital. He was a scoutmaster, coached Little League, attended soccer games and PTA meetings and enjoyed savoring a couple of glasses of wine over dinner with his family every night.

Then, in February of 1993, shortly after he, along with other Bush staffers, left the White House, Benedi got sick. “One Friday night I caught the flu,’ he recalls. He couldn’t shake it off. By early Wednesday morning, his wife sensed something terribly wrong and called an ambulance. By the time Benedi arrived at Fairfax Hospital, he had lapsed into a coma precipitated by catastrophic liver failure. He was 37 years old and wasn’t expected to live through the night.

For three days he clung precariously to life, waiting for an organ donor, tethered to life supports and sustained by massive blood transfusions (more than 240 people donated blood for Benedi, including 85 White House Secret Service agents). By Friday, doctors decided to pull the plug. A priest gave Benedi his last rites. Then, at the last minute of the 11th hour, a donor became available at the very same hospital.

What caused Benedi’s liver to fail was a combination of his history of moderate drinking and sensitivity to acetaminophen, the active ingredient in Tylenol. (Benedi notes he was not drinking at the time and that he never exceeded the recommended dosage.) Benedi, who now takes an arsenal of costly rejection-preventing drugs that are destroying his kidneys, sued Tylenol’s maker, McNeil Consumer Products Co., a subsidiary of Johnson & Johnson. He contended that company officials had known of the life-threatening risks of alcohol and acetaminophen but had neglected to warn doctors and consumers because they feared jeopardizing the reputation of Tylenol, the No. 1 over-the-counter pain reliever.

Cases of people who used alcohol regularly and who became stricken with liver toxicity after ingesting acetaminophen started appearing in the medical literature in the late ‘70s. Of the 200 patients who have been identified since, about 20% have died of complications stemming from catastrophic liver failure, says Dr. Hyman J. Zimmerman, professor of medicine emeritus at George Washington University Medical School and an expert in liver toxicity.

“This drug in large enough doses is a potent toxin for the liver,’ he says. “Even doses considered safe can lead to serious injury in individuals who drink regularly or are fasting. But for a quarter of a century, the problem was overlooked.’

“No question, Tylenol is the safest of the OTC drugs,’ says Dr. Brian L. Strom, chair of the department of biostatistics and epidemiology at the University of Pennsylvania School of Medicine. “But where people run into trouble is when they take too many.’

A jury agreed with Benedi and awarded him $8.8 million in damages. McNeil appealed, but the appellate court sided with Benedi. The court said: “We find that Benedi introduced sufficient evidence from which a reasonable jury could find that McNeil acted with reckless indifference to the health of its consumers.’ Tylenol now carries a warning written by the FDA to alert consumers to this danger.

Benedi’s unnerving story indicates that no drug is completely safe, not even Tylenol, which is currently used by more than 55 million people a year. It could be lethal in rare instances.

Acetaminophen isn’t the only popular over-the-counter medication that’s been linked with unpleasant, and in a few cases deadly, side effects. Investigators at Emory University in Atlanta, for example, were surprised to discover that of 421 hospital patients admitted with bleeding stomach ulcers, more than half had taken NSAIDs such as ibuprofen and aspirin. The researchers believed that these OTC drugs could be “an important health hazard’ that might be “one of the most important precipitating factors for ulcer-related hemorrhage.’

In 1992, Boston University School of Public Health researchers discovered that newborns stricken with a birth defect of the abdominal wall were more likely to have mothers who took an OTC decongestant containing pseudoephedrine, an ingredient found in Actifed, Advil Cold and Sinus, Dristan Sinus Caplets, NyQuil and Sudafed, among others. “This is a preliminary finding,’ cautions Martha M. Werler, the epidemiologist who did the research. “But what is relevant is that these medications are very popular and taken relatively casually. We don’t really understand the relationship between them and a wide variety of reproductive outcomes.’

OTC medications can also dull the effects of prescription drugs or interact with them to cause serious adverse reactions. Mixing pseudoephedrine--or ephedrine, phenylephrine or phenyl-propanolamine, a tongue-twisting lineup of similarly acting chemicals contained in such cough and cold remedies as Allerest 12-Hour, Dimetapp Elixir and Tavist-D--with a class of anti- depressant drugs known as monoamine oxidase inhibitors could cause serious reactions, according to University of Washington pharmacologist Philip Hansten. This synergistic witch’s brew can trigger any number of unpleasant symptoms--from nausea, fever and dizziness to dangerously high elevations in blood pressure that make a person susceptible to brain hemorrhages, seizures and deadly strokes. In the United States during the past three years, one woman died and three others were hospitalized after combining cold medications with these antidepressants.

Some laxatives can interfere with the efficacy of blood pressure drugs like Tenormin and the heart medicine Lanoxin. And popular calcium-based antacids such as Rolaids and Tums, or Mylanta II, which contains aluminum and magnesium, can cut the absorption rate of some antibiotics by as much as 90%.

“Not only would you be wasting your money on expensive antibiotic therapy,’ notes pharmacologist Graedon, “but a serious infection might not be cured.’

What’s equally disturbing, pharmacists and doctors say, is that regular use of potent OTCs can mask warning signs of a serious disorder. Apparently that is what happened to 17-year-old model Kristen Taylor, the younger sister of supermodel Niki Taylor. In the early morning hours of July 2, 1995, Niki discovered her sister lying unconscious in their parents’ South Florida home. All attempts at resuscitation failed, and Kristen was pronounced dead at a local hospital an hour later. An autopsy report revealed that Taylor had died from a bronchial asthma attack. Her illness may have gone undiagnosed because she relied on an over-the-counter inhalant; its effectiveness in easing her breathing problems hid the extent of her disease.

Consumer watchdog groups, like Public Citizen, and many pharmacists worry that stories like these will become more common. Because of the easy availability of powerful OTCs, people diagnose themselves rather than rush to a doctor, and they fail to recognize the symptoms of a more serious illness. Recurrent yeast infections, for instance, can be a symptom of AIDS or cervical cancer, says pharmacist Smarinsky, and according to Dr. Joel Richter, a gastroenterologist at the Cleveland Clinic Foundation, the stomach pains treated by the newer OTC acid blockers like Pepcid AC or Zantac 75, which in prescription strength have been used to combat ulcers, could indicate any number of gastric disorders, from ulcers to stomach cancer.

In fact, a July 1996 Stanford University study revealed that arthritis patients who self-medicate with antacids to prevent the gastric distress triggered by habitual use of NSAIDs are twice as likely to be hospitalized with gastrointestinal complications. “Gastro- protective agents like Tagamet or Pepcid,’ says Stanford’s Dr. James F. Fries, who conducted this research, “can mask symptoms and permit more serious things to happen.’

Obviously, these cases are extremely rare. And drug makers insist they wouldn’t have occurred if consumers had simply followed the directions on the label. “We spent millions of dollars on clinical studies and on label-comprehension work,’ says George Quesnelle of SmithKline Beecham, makers of Tagamet and Nicorette gum. “And the directions are clear: If you take a drug, you should not take it for more than a specified period of time, and if pain persists, you should see your physician.’

Adds David Thueson, a pharmacologist and author of “Thueson’s Guide to Over-the-Counter Drugs’: “It’s people who push it beyond reasonable limits’--doubling and tripling recommended dosages and taking it for long periods of time--”that really get into trouble.’

Predicting side effects in a diverse population can be tricky, though, because there’s such a wide variation in individual response to drugs. When drug makers test new medicines in large clinical trials, which can encompass as many as 6,000 to 7,000 people, subtle sensitivities or differences in metabolizing a drug may not be detected. “Even the large, well-designed clinical trials that are conducted to gain pre-market approval cannot uncover every problem that can come to light once a product is widely used,’ wrote FDA Commissioner David A. Kessler in a 1993 article in the Journal of the American Medical Assn. “If an adverse event occurs in perhaps one in 5,000, or even one in 1,000 users, it could be missed in clinical trials but pose a serious safety problem when released to the market.’

Once millions--not just thousands--are consuming a medication, the potential for trouble expands exponentially. But it’s impossible to list all these possible side effects on even the FDA’s new consumer-friendly warning labeling, and consumers don’t have the knowledge to make an informed choice. Compounding the problem, says Dr. Marvin M. Lippman, chief medical advisor for Consumers Union, publisher of Consumer Reports, is the prevalent “more is better’ attitude: “If two tablets are good,’ he says, “people assume that four will be even better,’ which can lead to disastrous overdose or ingesting prescription-strength dosages without the supervision of a physician.

On top of that, “there is a huge population that either does not or cannot read labels and does not or will not comply with directions,’ says Lorie Rice, an associate dean of the University of California at San Francisco School of Pharmacy. One 1995 survey, which was published in the Journal of the American Medical Assn., revealed that a staggeringly high percentage of patients--as many as 61%--at public hospitals in Atlanta and Los Angeles couldn’t understand what was written on prescription packages. If they cannot read a prescription label when they’re under a doctor’s watchful eye, what happens when they hurriedly dash into their local minimarket for something to relieve their headache?

Even for consumers who dutifully scrutinize package inserts, deciphering what’s on the list of active ingredients can be daunting. Especially since people buying medicine are, more often than not, sick. And, as Knapp points out, “people who are sick are vulnerable.’

IN THE MAIN CONFERENCE ROOM OF FDA headquarters, located in a nondescript concrete-and-glass building in a Washington suburb, is a picture of a Victorian woman handing her last dollar to a faith healer. The FDA came into being in 1927 as the Food, Drug and Insecticide Administration to ensure that unwary consumers would never again be bilked by charlatans. In the 70 years since, this chronically underfunded agency, which is woefully outflanked by the forces of the industry it polices, has racked up a remarkable safety record.

Nevertheless, the modern era of the FDA was ushered in by a narrowly averted public health catastrophe. In 1960, an uncompromising FDA scientist named Dr. Frances O. Kelsey stubbornly delayed approval of a nonprescription sleeping pill that was popular in Europe. The drug was thalidomide--which caused terrible deformities in some newborns, afflicting them with short, flipper-like arms. Kelsey, now in her 80s and still working at the FDA, became a national heroine.

Haunted by the specter of what could have happened had Kelsey been less vigilant, Congress enacted the Kefauver-Harris bill in 1962, which armed the FDA with the legal clout to keep worthless and dangerous potions off the market, to get rid of quack remedies already in use and to demand much higher quality scientific data from companies seeking approval of new drugs. It wasn’t until 1972, however, that the agency began a systematic review of the safety and effectiveness of the 730 active ingredients used in the more than 300,000 drug products sold in the United States. As a result of this evaluation, some ineffective ingredients were removed from the market, others were banned because they were dangerous and still others were deemed safe enough to be dispensed without a prescription.

Switching prescriptions to OTC status achieved much higher visibility in 1991, however, when FDA Commissioner Kessler created a separate OTC drug office--as well as a Nonprescription Drug Advisory Committee, composed of independent scientists and representatives of the public, to review product switches.

“The FDA is now doing a much more careful, thoughtful job of drug screening,’ says the University of Pennsylvania’s Dr. Brian Strom. “The older OTC drugs that were grandfathered in are probably less safe than the new ones.’ The old saw, in fact, is that aspirin--a potent pain reliever that can cause such side effects as stomach bleeding, nausea and heartburn--would never get OTC clearance from today’s FDA.

Prescription drugs now applying for OTC status must meet several stringent criteria before even being considered: They must have a history of safety and efficacy, and the drug makers must demonstrate that consumers can diagnose the problem themselves and that the product can be used without the intervention of a health-care professional.

“We tend to be very conservative,’ says Randy Juhl, dean of the University of Pittsburgh School of Pharmacy, who for four years chaired the FDA’s Nonprescription Drug Advisory Committee. “Safety is always a big concern. All the drugs have a long history of prescription use, so it was hard to imagine something would pop up that we didn’t know about. But we still worry whether people read the label and about how people are going to use the drug. Is there a way to misuse it that we haven’t thought of?’

Some problems slip through the cracks, however. A disturbing 1990 study by the General Accounting Office, the investigative arm of Congress, revealed that half of all prescription drugs have serious post-approval risks and could cause adverse reactions that lead to severe or permanent disability or death (subtle problems with drugs often don’t surface until millions of people are taking them).

In the wake of this stunning revelation, the FDA’s Kessler dispatched 20 extra field investigators to do more audits of drug tests, and instituted MedWatch, an approval surveillance program that makes it easier for manufacturers and health professionals to report problems. “Only about 1% of serious events are reported to the FDA,’ Kessler noted when he introduced the program in 1993. Last year, the agency received 140,000 reports, about half of which concerned extremely serious drug reactions that resulted in death or disability, or required surgery or hospitalization to prevent permanent impairment.

But Dianne L. Kennedy, MedWatch’s director, admits that they’re still only scratching the surface. “We’re getting reports of about 10% of adverse reactions,’ she says, “which means there could be over a million incidents a year--though nobody really knows.’

“This is a purely voluntary system, and all of the motivation is on the side of noncompliance,’ maintains Graedon, who believes there’s a hidden epidemic of unreported adverse drug reactions. “No one gets rewarded for saying, ‘I had patient who died. There’s always the possibility of litigation. And if this is the case with prescription drugs, what happens with OTCs?’

In fact, when someone experiences unexpected side effects from an OTC drug, the tendency is to blame the symptoms on their illness, rather than an adverse drug reaction. So they don’t report the symptoms, and, as a consequence, the problem is never detected.

Sometimes, it can take decades for a disorder to be tracked back to its source. Hexachlorophine soap, an antiseptic scrub that was introduced in 1936, is a prime example. Hospitals used the cleanser to wash everything, from scrubbing surgeons’ hands to bathing babies with diaper rash. In the late 1960s, doctors finally realized that the product had caused irreversible brain damage in some newborns. “We had almost 30 years of use of this soap,’ says Samford’s Dr. Tim Covington, “before it was pulled off the market.’

And even when the FDA is faced with incontrovertible evidence, says Graedon, the agency is often slow to respond. Consider the case of Seldane, an antihistamine that was on the verge of going OTC in 1991. Seldane was introduced in 1985, amid much fanfare, as the first allergy treatment that didn’t cause drowsiness. Allergy sufferers quickly made it the 10th-most prescribed drug in the country, even though alarming reports about life-threatening drug reactions and adverse interactions with anti-fungal medicine and antibiotics were trickling in to the FDA, according to Graedon. But it wasn’t until 1992, seven years and millions of prescriptions later, that warning letters were fired off to the nation’s doctors, alerting them of the dangers. In the interim, 64 patients suffered from irregular heartbeats, 16 more were stricken with heart attacks and four people died. Seldane never was granted OTC status.

Episodes like this have prompted pharmacists to champion the creation of another category of drugs, a middle-ground category somewhere between prescription and OTC, to be dispensed exclusively by pharmacists (countries like Denmark, France, England, the Netherlands and Canada have a third or even fourth class of drugs). Then they could counsel customers, answer questions, warn them of potential dangers, possibly determine whether someone has a more serious disorder--and even do some follow-up.

“There were drugs like this when I was a kid,’ recalls pharmacologist/author Dr. David Thueson, “medications that were dispensed from behind the counter, and even some that people had to sign for--like codeine for coughs, which can be habit forming.’

Consumer groups such as the National Consumer League--along with the American Pharmaceutical Assn., a professional organization for pharmacists--have led several charges up Capitol Hill, because they believe that consumers need help navigating the seas of OTC. “The public is highly stratified in their knowledge level, sophistication and literacy,’ says Lippman of Consumers Union. “One-size package doesn’t fit all.’

The FDA and the drug industry, however, have consistently rejected the additional-category concept as cumbersome and unnecessary. They insist that today’s more educated consumers can tell the difference between a stomach ache and a stuffy nose. Says the FDA’s Dr. Debra Bowen: “If we say these drugs are safe without the intervention of a health professional, then we should mean it.’

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The Big Guns

The FDA since 1976 has approved 68 prescription-to-OTC switches, 33 since 1886. In 1995, 300,000 OTC products rang up sales of $16.1 billion. Nine of today’s top 20 OTC medicines would have required prescriptions 20 years ago.

Brand name: Advil (switched 1984)

Company: American Home Products

1995 sales in millions: $380

Brand name: Excedrin (switched 1982)

Company: Bristol-Myers Squibb

1995 sales in millions: $150

Brand name: Benadryl (switched 1985)

Company: Warner-Lambert

1995 sales in millions: $125

Brand name: Aleve (switched 1994)

Company: Procter & Gamble

1995 sales in millions: $125