When drugs don't mix

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A 29-YEAR-OLD WOMAN took the allergy drug Seldane (generic name, terfenadine) to control her nasal congestion. She was also taking Nizoral (ketoconazole) to cure toenail fungus. The two drugs interacted.

One week later she went to the emergency room after fainting, and three days later died after a cardiac arrest.

How many people die from accidents like this one? The number can only be guessed at, since doctors are not required to report such cases to any central database and in many instances are not aware of what killed a patient.

The inventiveness of drug companies is both a blessing and a curse.

There are now thousands of drug compounds on the market to treat all manner of maladies that went untreated a generation ago. But they have also created a dangerous expectation among patients that every ailment has a pill. The result is what doctors call "drug cocktails," mixtures of several potent chemicals that could interact in unpredictable ways.

Drug cocktails have acquired legitimacy from several lifesaving applications. For certain strains of tuberculosis you need a cocktail of four antibiotics to kill the bacterium. You need a cocktail of four to six antiviral drugs to quell AIDS. But are cocktails worth the risk for lesser ailments?

Six million Americans popped "fenphen," a combination of fenfluramine and phentermine, to control their weight before it was discovered that this drug combo was linked to damaged heart valves.

We know of one 56-year-old nurse in Denver who takes Depakote (divalproex sodium, a mood stabilizer), Tofranil (an antidepressant), Novane (thiothixene, for neural disorders), Desarill (trizodone, a sleeping pill), plus an assortment of other prescription drugs to control her anxiety.

She rationalizes away the risk: "I'm a nurse -- I know what to watch for and what to ask my doctor."

But the doctor may not know, and besides, not every person has the kind of access to medical advice a nurse has. One 30-year-old artist in New York mixes up this mostly over-the-counter cocktail to treat a chronic bug which, she says, she gets about once a month: Tylenol for the headache, NyQuil to help her sleep, an antihistamine for allergies, chamomile tabs for indigestion, St.-John's-wort (a much-touted "natural"antidepressant) for the winter blues and echinacea (an herb purported to be a cold preventive), along with a prescription for Antivert (meclizine, for nausea and dizziness).

So far, she hasn't shown signs of liver damage. Maybe she's just lucky.

"AIDS provided an opportunity to institutionalize [drug cocktails],"

says pharmacologist Joe Graedon, coauthor of The People's Guide to Deadly Drug Interactions (St. Martin's Press, 1995). "Now it's not uncommon for people to take half a dozen pills, most of them to counter side effects [of the other drugs]."

Some dangerous interactions are known (see table). A lot aren't. How could the drug manufacturers know them all, even if their products are well tested? Any number of combinations can be made from the thousands of drugs on the market today.

A single drug can sometimes behave differently from person to person.

Adding a second drug more than doubles that variability by introducing the possibility of interactions, some of which can produce horrendous side effects.

Calcium channel blockers, taken to reduce blood pressure, can produce a dangerous spike in that pressure when given with the antituberculosis drug cocktail of Rifadin and Rimactane (rifampin). That's because the cocktail causes the channel blockers to lose their effectiveness.

Serious heart problems can result from combining some diuretics (also used to treat hypertension) with the painkillers Advil or Motrin.

Antidepressants such as Prozac, Paxil (paroxetine) and Zoloft (sertraline) can be life-threatening when combined with Eldperyl (selegiline), Marplan (isocarpoxazid), Nardil (phenelzine) and Parnate (tranylcypromine) -- and can be dangerous taken with some anticonvulsants.

It can take years before data are gathered together, conclusions drawn and warnings issued. Doctors were still prescribing Seldane to patients also on Nizoral nearly five years after it was discovered that this cocktail could kill. It took the Food & Drug Administration and Seldane's thenmanufacturer, Marion Merrill Dow, another two years to acknowledge the problem.

Do you really need all those pills? "That's a question for your doctor," says Dr. James Lipsky, director of clinical pharmacology at the Mayo Clinic. "But in this age, where everybody has many doctors, you've got to make sure that each one of them knows what the other one prescribed." Don't forget to tell them if you're taking vitamins or herbal remedies. Medicine is a wondrous thing, but it can't free us from all the aches and pains of the human condition. If you must mix pills, read the cautions on the patient package insert carefully. Make sure your pharmacist has a computer system that will flag dangerous combinations.