Smaller dosages may ease side effects and cut drug costs, too


June 14, 1994|By Doug Poldolsky | Doug Poldolsky,Los Angeles Times Syndicate Sun staff writer Sandra Crockett contributed to this article.

Call it "lite" medicine. Researchers are now finding that smaller-than-usual doses of a wide range of drugs pack as potent a wallop as the standard amounts. What's more, cutting the dosage back -- sometimes by 50 percent or more -- can mean far fewer side effects and in some cases dramatic cost savings.

No fewer than 183 drugs now are sold with information for doctors on "low dose" use. Over the past year, more than 200 studies have been published on the safety and efficacy of low-dose drugs aimed at such conditions as high blood pressure, osteoporosis, ulcers, high cholesterol and depression.

The results may especially intrigue people who aren't able to tolerate traditional treatments. About 15 percent of all patients who try the antidepressant Prozac, for example, can't bear early side effects such as nervousness and insomnia. People suffering panic attacks seem especially sensitive.

So researchers at the University of California Medical Center in San Francisco tried a stepped approach. They started 133 patients on only 5 milligrams a day -- a quarter of the standard dose -- and gradually increased the dosage over a week's time. In all, 37 could not tolerate the full 20-milligram strength. But while 22 patients quit the study, 15 showed improvement on doses averaging only 10 milligrams. People with panic disorder particularly benefited from reduced doses, the researchers concluded. Study author Alan Louie points out that low-dose patients were not tested against people given placebos. Nevertheless, he believes the strategy is reasonable for doctors to consider.

Likewise, half doses of Lovastatin may suffice to keep cholesterol levels in check. A study of post-menopausal women reported Feb. 9 in the Journal of the American Medical Association found that most who followed the low-dose approach brought their blood levels of low-density lipoproteins, the "bad" cholesterol that clogs arteries, back to the desirable range.

The research team at the University of Texas Southwestern Medical Center reported that only 10 milligrams of Lovastatin a day rather than the normal 20 milligrams lowered total cholesterol of most women in the study by 19 percent, triglycerides (another fat component) by 16 percent and LDL cholesterol by 22 percent. Levels of high-density lipoproteins, the "good" cholesterol, weren't affected.

Since the researchers found that 10-milligram Lovastatin tablets weren't much cheaper than the 20-milligram pills, patients were prescribed the higher dose and told to break them in half. That approach does not work with all medications -- pills with protective coatings or those designed to dissolve very slowly, for instance. And patients should never alter their own doses without consulting a doctor or pharmacist -- both of whom are directed in their prescriptions by a higher source.

"The FDA makes a decision on the most effective dose," says Dr. Babette Duncan, director of the Drug Information Center at the University of Maryland Medical Center. The FDA tests drugs for their toxicity and side effects. "Every drug has a side effect," she says. "The goal is to have the least amount."

The marketing potential of "lite" drugs hasn't been lost on pharmaceutical companies. Last year, Rhone-Poulenc Rorer got the nod to sell a low-dose, 1.25-milligram version of its hypertension drug Lozol.

And in March, Lederle Labs and Procter & Gamble jointly introduced Ziac, a high-blood-pressure combination drug that contains both a beta blocker and a diuretic in fractions of the standard dosages. Of 550 patients given either a beta blocker or a diuretic at normal doses or Ziac for up to 12 weeks, those on the low-dose combo therapy had the best luck controlling their blood pressure with the fewest side effects.

Problems such as impotence and slowed heartbeat struck fewer than 1 percent of patients on Ziac. About 3 percent of patients on standard doses of diuretics become impotent, and at least as many who take beta blockers may experience an abnormally slowed heartbeat.

In March, Bristol-Myers Squibb introduced a low-dose version of its estrogen replacement drug, Estrace, aimed at preventing osteoporosis in women past menopause.

As Estrace illustrates, some lite drugs involve trade-offs. Research suggests that the new 0.5-milligram dosage causes far fewer side effects -- such as unwanted vaginal bleeding -- than do higher dosage regimens. But over the long term, it works less well against bone loss, according to a California study of 63 postmenopausal women.

Still, "many women might accept a slightly lower level of protection against osteoporosis in exchange for fewer side effects," says Harry Genant, director of the osteoporosis research group at the University of California at San Francisco.

Such cost-benefit ratios should be explored with a doctor or pharmacist. That may require some persistence, since both naturally tend to stick to drug makers' recommendations. But finding the lowest effective dose can make both the medicine and the drug bills easier to swallow.

Doug Poldolsky writes for U.S. News & World Report.

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