GAMBLING WITH YOUR HEALTH? JUST BECAUSE THEY'RE ADVERTISED ON TV DOESN'T MEAN NEW PRESCRIPTION MEDICATIONS ARE SAFE.

Byline: Mariko Thompson Staff Writer

One person's miracle drug is another person's poison pill.

For Encino resident Elaine Sherman, Lotronex worked. But the medication, recalled in 2000 after only 10 months on the market, was fatal to some. Lotronex, which treats irritable bowel syndrome, was pulled when side effects forced some patients to have portions of their colons removed. At least five died.

That didn't deter Sherman from seeking the drug, the only one that had worked for her in 20 years of visiting gastroenterologists, homeopaths and nutritionists.

``I tried other countries, and nobody had it but us,'' Sherman said. ``I called pharmacies in Canada. I had friends check the Internet.''

Sherman wasn't alone in her quest. The FDA was swamped with calls from Lotronex users lobbying for limited access to the drug.

The story of Lotronex captures the complexities that surround the issue of drug safety, a web formed by the FDA, pharmaceutical companies, doctors and patients. All have a part to play. The FDA must thoroughly test a pharmaceutical company's drug, doctors must heed warnings before prescribing a medication and patients must adequately weigh pros and cons.

Follow each step, experts say, and it's still a gamble. There's no such thing as the perfect pill. Reactions to drugs are individual and vary with gender, race and age.

The me-too phenomenon

A recent study published in the May 1 issue of the Journal of the American Medical Association shows that the risks posed by new drugs entering the market may be substantial. The study, led by Dr. Karen Lasser of Cambridge Hospital and Harvard Medical School, found that one in five new drugs produced significant side effects that were not discovered until after FDA approval.

Of 548 drugs approved between 1975 and 1999, 56 - roughly 10 percent - later received warnings of serious side effects or were recalled. The figure rose to 20 percent for drugs approved toward the end of the time period studied. The study recommended doctors avoid prescribing new drugs in favor of older established drugs, unless the new drug represented a breakthrough.

A rebuttal piece by Drs. Robert Temple and Martin Himmel of the FDA argued the study overstated the dangers. Drug trials involving a few thousand patients might not reveal all adverse effects - some of them rare - that appear when a drug enters the general population, they wrote. They also saw no need for doctors to wait before prescribing a newly approved drug.

``It is worth observing that existing therapy does not always prove to be completely safe and fully satisfactory and that there is value in having alternatives,'' they wrote.

Local physicians say the study reinforced their belief in proceeding with caution when considering new drugs. Patients suffering from a terminal illness have little to lose. But many drugs introduced to the market are ``me-too drugs,'' one company's version of an existing product.

Taking a chance

``If I had a life-threatening disease, I might take the risk,'' said Carlo Michelotti, chief executive officer of the California Pharmacists Association. ``If it's a me-too drug, I wouldn't be anxious to jump on the bandwagon until it had some history.''

Dr. Kenneth Murray, a family practitioner in North Hollywood, said he waits six months to a year before prescribing new nonbreakthrough medications to his patients. At Providence St. Joseph Medical Center in Burbank, Murray also serves on a committee that determines which drugs to stock at the hospital.

``Compared to 20 years ago, pharmaceuticals today are much more powerful drugs,'' he said. ``The potential to cause harm is enhanced. They really have tremendous effects on the body.''

Doctors say they have a responsibility to prescribe medications properly and monitor the results. Both doctors and pharmacists also must consider drug interactions. Even a drug as seemingly benign as aspirin or ibuprofen can have an adverse effect if taken by the wrong person, said Dr. Michael Hirt, an internist and director of the Center for Integrative Medicine at Encino Tarzana Regional Medical Center.

With Lotronex, some doctors didn't pay attention to the patient profile, said Hirt, who treats Sherman. Lotronex was approved for women with chronic diarrhea caused by irritable bowel syndrome. But some doctors prescribed the medication to IBS sufferers with constipation - a factor in some but not all of the problem cases, according to the FDA.

The FDA and Lotronex maker GlaxoSmithKline continue to discuss a plan that would allow the medication to be prescribed in specific circumstances, said FDA spokesman Jason Brodsky.

``There are two sides to every drug withdrawal,'' Brodsky said. ``Lotronex is a case in point where the benefits of a drug for some meant a dramatic improvement in the quality of life. But for others, the product had serious effects.''

Dr. Greg Thompson runs the Los Angeles County-USC Drug Information Center, which advises health professionals on drugs, including dosages and side effects. He is critical of efforts to revive Lotronex even under restricted conditions.

``This isn't cancer,'' Thompson said. ``Irritable bowel syndrome isn't worth losing your colon over.''

Thompson said doctors and pharmacists need to be more vigilant in reporting adverse reactions to the FDA's MedWatch. The JAMA study estimated that less than 10 percent of adverse effects are reported to MedWatch. Thompson also would like to see a formal last phase added to drug trials in which physicians are required to report adverse effects for at least a year after approval.

``In theory, doctors are supposed to do that now,'' he said. ``But it's a passive participation. We need to be active.''

As seen on TV

The impact of direct marketing by pharmaceutical companies is yet another piece of the drug-safety puzzle. Doctors say patients often demand the medications they see advertised, with little knowledge of the risks.

The JAMA study noted that new drugs are heavily marketed to both doctors and consumers, which means they may be in wide distribution before adverse effects are known.

``I don't feel pharmaceutical companies should market to patients,'' said Dr. David Wong, an internist who serves on the committee that oversees pharmaceuticals at Kaiser Permanente in Panorama City. ``Good marketing is what sells these days.''

In his North Hollywood practice, Murray has seen the effects of this marketing. For years, he has known birth control pills can also reduce acne and, like many doctors, has prescribed them for this off-label use. The makers of one pill took the unusual and costly step of returning to the FDA to get approval for this added use. After television commercials aired for Ortho Tri-Cyclen, many of Murray's female patients asked to switch to that brand.

``It's brilliant marketing,'' Murray said. ``The company can accurately say it's the only birth control pill so approved. The truth of the matter is they all do that.''

Doctors, too, if they have success with a particular medication, can be swept up by hype. So what's a patient who wants to make smart decisions about medications to do?

The main thing patients can control is how educated they are about the medications they take, experts said. Patients should have detailed discussions about benefits and risks with their doctors and pharmacists.

Another thing doctors and patients can do is increase the focus on wellness. Preventive measures such as nutrition and exercise should be the first line of defense, Wong said.

``People want the magic pill,'' he said. ``The truth is, everything has a side effect. There's no free gift.''

The path of new drugs

THE PROCESS of testing a new drug is like drilling for oil. The pharmaceutical company might spend millions of dollars and end up with a dry run.

But sometimes, the side effects that appear in those dry runs become medical breakthroughs. In perhaps the most celebrated case, the erectile dysfunction drug Viagra was originally tested as an anti-hypertension drug.

In other cases, drugs deemed highly toxic are found to have beneficial uses. Thalidomide, a morning-sickness drug banned in 1961 for causing serious birth defects, has been found effective in treating leprosy.

To receive approval by the Food and Drug Administration, the drug must complete three phases of clinical trials.

In Phase 1, initial studies are conducted with a small pool of volunteers, usually between 20 and 80 people. The studies provide preliminary data on effectiveness, how the drug should be administered, and side effects associated with increasing doses.

In Phase 2, several hundred people are tested to determine short-term side effects and risks associated with the drug.

In Phase 3, the trial tests several hundred to several thousand people. The studies form the basis for extrapolating effectiveness and safety to the general population.

As a condition of approval, the FDA may require a fourth phase where the company continues to evaluate the drug once it enters the market.

Critics of the process say the pharmaceutical companies exert too much influence on the FDA. Under fast-track legislation passed by Congress in 1992, the FDA began charging user fees to pharmaceutical companies. The fees allowed the FDA to hire more staff and cut approval time in half.

``Any entity is going to pay attention to the people who pay the bills,'' said Dr. Kenneth Murray, a North Hollywood family practitioner.

The FDA, however, says neither safety nor the agency's neutrality has been compromised, noting the recall rate has remained constant - about 2.7 percent before user fees and 2.8 percent after user fees.

``Some people say, 'Let's extend the process and make it longer,' '' said Dr. Michael Hirt, an internist and director of the Center for Integrative Medicine at Encino Tarzana Regional Medical Center. ``I'm not sure that's the answer. We still have one of the best systems around.''

- M.T.

CAPTION(S):

3 photos, box

Photo:

(1 -- cover -- color) DRUGS OF CHANCE

Raising profile of new prescription medications creates a precarious balance

(2) no caption (roll of the dice, medicine)

David Sprague/Staff Photographer

(3) no caption (roulette table)

Box:

The path of new drugs