This guideline was very similar to the 1990 FDA guideline in intent. It requested that:
1. Studies should be done in new molecular entities (NMEs) or new chemical entities (NCEs) likely to be used in the elderly, either to treat a disease of aging or because the disease is also common in the elderly.
2. Studies should include patients 65 years and older, and preferably patients aged 75 or older, and advised against arbitrary age cutoff (patients aged 60-65 are not considered elderly).
3. Meaningful numbers, especially in Phase III: a minimum of 100 patients was suggested for a non-geriatric specific disease (e.g. hypertension).
4. Analysis of the database for age-related differences of efficacy, adverse events, dose, and (gender) relationships. A geriatric database may contain data from the main Phase II, III studies or from a geriatric-specific study.
5. Pharmacokinetic studies (PK), either formal pharmacokinetic studies or on a population basis. For the latter, a blood sample is taken from many patients on up to four occasions. The time of dosing is recorded, and the time of samples. The patients must be at 'steady state'. This way, an adequate population PK plot can be built.
6. Pharmacokinetic studies in renal impaired patients if the drug or metabolites are renally excreted. If the NME is excreted and/or metabolized by the liver, a hepatic-impaired study should be undertaken. These studies do not have to be done in elderly patients (they are usually done on a new NME anyway).
7. Usually, differences in the therapeutic response or adverse events are too small to detect at an equivalent plasma level between ordinary adult and elderly patients to make this a requirement. However, separate studies are requested of sedative hypnotic psychoactive drugs or drugs having a significant CNS effect, and, similarly, if Phase II, III studies are suggestive of an age-related difference.
8. Drug interaction studies should be done on digoxin and oral anticoagulants, for these drugs have a narrow therapeutic range and are commonly prescribed in the elderly. These drugs frequently have their serum levels altered by other drugs. Where drugs are heavily metabolized by the liver, the effect of drug enzyme inducers and inhibitors should be explored. Similarly, drugs which will share the same cytochrome P450 enzyme pathways should be tested. Ketoconazole, macrolides, and quini-
dine are given as examples. Finally, other common drugs most likely to be used with the test drug are recommended to be explored for possible synergis-tic or antagonistic drug interactions.
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