Testing Drugs in Older People

by Food and Drug Administration (FDA)

While a 10-milligram dose of Valium (diazepam) for a 35-year-old man might relax his muscles, the same dose might make a 75-year-old woman so relaxed that her muscles lose coordination, causing her to fall and break her hip.

A therapeutic dose of many medications for a younger person may be too strong for an older person.

Bodies change as we get older. With age, muscle tissue declines and fat accumulates, the liver slows down, brain cells change in sensitivity, and our kidneys don't work as efficiently. In fact, the kidney loses one-third of its function between the ages of 30 and 90, and about one-third of people develop a fairly big loss. Because of these changes, drugs may stay in the bodies of older people longer.

Recommended doses of a particular drug are based on pre-market clinical testing evaluating the drug's effectiveness in a few thousand people. Though many people have the impression that drug companies have usually tested drugs exclusively in young individuals, in fact, older people have long been included in clinical studies. However, in the past, there was little attempt to see whether older people responded differently.

In 1983, for instance, according to Robert Temple, M.D., director of the Food and Drug Administration's Office of Drug Evaluation I, FDA analyzed a dozen pending or recently approved new drug applications. Temple said that all the applications included significant numbers of patients over 60 (generally about a third), and in most trials, 5 to 10 percent of patients were older than 70. But the study results were not broken down and compared by age groups. Therefore, if there were differences in response to drugs, these differences were not detected.

Agency Issues Guidelines

To encourage the gathering of reliable data on the effect of drugs on the elderly, FDA recently issued guidelines for pharmaceutical firms. The guidelines were developed over several years and have already had an effect. A 1988 survey of approved drugs showed researchers compared response data from younger and older patients. In addition, most studies included data on excretion of the drug by older patients.

The guidelines ask that, in doing drug studies, manufacturers determine whether a drug is likely to have significant use in the elderly, and, if so, include elderly patients in clinical studies. These studies should then include analysis of effectiveness and adverse effects by age.

Temple explains that studies need to answer two basic questions about how a drug acts in the elderly. First: What does the body do to the drug (metabolism, absorption, distribution, and excretion)? This is known as pharmacokinetics. "Older people handle a drug differently — not necessarily because of age itself, but because they are more likely to have other illnesses or to be on other drugs that can interfere with the metabolism of the very drug they are given. Decreased kidney or liver function, or heart failure, or diminished muscle mass for example, all can affect the body's handling of a drug," Temple said. "This is a major cause of difference in response between young and older people."

The second question is: What does the drug do to the body? This is the pharmacodynamics of the drug. Older people, for example, may be more responsive to drugs that are sedating, or may be more likely to get dizzy or confused from these drugs.

To discover whether older people handle drugs differently from younger people (that is, whether the drug has different pharmacokinetics in the elderly), the guideline suggests two choices: (1) a specific pharmacokinetic study in older persons; and (2) preferably, an attempt to discover all of the causes of variability in pharmacokinetics (because the elderly are more likely to have such problems apart from their age), through use of a "pharmacokinetic screen."

Test Relatively Simple

Temple explains that this is a relatively simple test, in which the researcher measures the concentration of the drug in the blood of all or most of the individuals who receive a particular drug. Only a few blood samples are necessary. The scientists can compare blood levels in various groups to see which factors increase or decrease the concentration of drug. With this information, they can determine how to adjust treatment according to age and other factors such as kidney or liver malfunction.

In addition to studies involving older and younger patients, the new guidelines suggest that "in some cases . . . especially for drugs targeted to older patients or where age-related differences or problems are anticipated, trials might be carried out specifically in the elderly." The guideline adds that attempts should also be made specifically to include people over 75.

The guideline also urges attention to possible interactions of the drug being studied with other drugs elderly patients might use. For instance, many drugs alter the pharmacokinetics of digoxin, a heart drug that is widely prescribed for the elderly. Because this interaction is potentially toxic, evaluation of how a drug affects digoxin is imperative, said Temple.

He added that FDA is developing regulations to require drug manufacturers to include a special geriatric use section in the physician's labeling of all drugs.

"Although a guideline is not strictly a requirement," Temple said, "it does describe an acceptable way to meet FDA's expectations. We certainly would be likely to ask a pharmaceutical manufacturer that had not done so to analyze the data as it pertains to the elderly." But, he adds, "we do not see resistance to this guideline. There is a general consensus among pharmaceutical firms that these guidelines are reasonable suggestions."

Simple Steps

While the guideline is expected to allow much more precise recommendation for use of drugs in older patients, all patients, and particularly older citizens, can take a few simple steps to ensure the safest possible use of drugs.

Here's a list of questions that may be helpful to ask the doctor (or the office nurse):

• What is the drug I'm taking?
• What is the drug supposed to do?
• What are the possible side effects?
• Is the drug habit-forming?
• Should I take the drug with food or avoid food when I take it?
• Should I avoid any particular activities, such as driving a car orexercising?
• At what times of the day should I take the drug?

Patients should be sure to tell their doctors about any drug allergies or other reactions they have had, and about all other medications they are taking, both prescription and over-the-counter. Some people find it useful to bring a list of the drugs they're taking to their appointments. Or they find it easiest to bring all their medications with them so that nothing is omitted and no misunderstandings occur.

The local pharmacist can also be a help. Pharmacy records include a person's name, address, list of allergies, chronic conditions, notations for new prescriptions and refills, and the name of the prescribing doctor. Patients can check their drug histories with the pharmacist and ask about possible drug interactions. For this reason, it's a good idea to go to one pharmacy for all prescriptions.

Do's and Don'ts

To further ensure the safest and most effective drug use, here are some commonsense do's and don't's.

Do call your doctor immediately if you notice any new symptoms or side effects, such as incontinence, confusion, sleeplessness, or impotence. Drugs can have a very wide range of effects. Never assume a change could not be due to the drug. If in doubt, check!

Do store medicines properly. This usually means storing them in a cool, dry place. Some medicine can be stored in the refrigerator. Check with your pharmacist first. The bathroom medicine cabinet is usually not the best place to store drugs. Bathrooms are warm, damp places, and some drugs may lose their potency if exposed to moisture.

Do read the labels and other information and instructions provided with the prescription.

Do throw away expired (or old) medicines. Dump and flush them down the toilet.

Do take the exact amount prescribed.

Don't take medicines in the dark. Turn on the light, and be sure you're taking the correct medicine.

Don't stop taking a drug suddenly without checking with your doctor — even if you feel better.

Don't take drugs prescribed for someone else or give your drug to someone else.

Don't transfer a drug from its original bottle to another.

Don't drink alcoholic beverages while you're taking medication unless your doctor says it's OK. Mixing alcohol with medicine can be dangerous. Of the l00 medicines most commonly prescribed, over half contain at least one substance that reacts badly with alcohol.

Finally, recognize that it is part of your doctor's job to discuss your medicines with you. If your doctor (or his staff) won't take time to talk with you, consider finding another doctor with whom you feel more comfortable and confident and with whom you can talk about possible drug effects.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.