Potential for adverse drug reactions and drug-drug interactions of multimedication in the aged: Results from the Berlin aging study

Due to the age-associated increase in morbidity, many elderly subjects are in need of multiple drug treatment. Multimedications, however, carry a high risk for adverse drug reactions (ADR) and drug-drug interactions (DDI). This risk is especially increased in very old patients since age and morbidity lead to significant changes in body composition and organ functions, Nonetheless, representative and specific information on cumulative risks for adverse effects of multimedications in the aged is not yet available. We used data of the ongoing, population-based Berlin Aging Study (N = 516; age range 70-103 years) to evaluate the cumulative potential for ADR and DDI in a subgroup of participants taking five or more drugs (N = 221; 44.4% of the parent population [estimated]; mean age 85.2 +/- 8.3 years). Computerized algorithms were used to screen all medications for potential ADR and DDI based on standardized information which was derived from the German Physician's Desk Reference and a frequently used textbook on ADR and DDI. As expected, the analyses revealed a significant potential for adverse effects of multimedications. Cumulative totals of 12 221 different potential ADR (54.9 per subject) and 1016 different potential DDI (4.6 per subject) were identified. With regard to ADR, the most prevalent ADR-risks were for gastrointestinal upset (99%), headache (96%), postural hypotension (95%), and vertigo (94%). With respect to these risks, the minimum mean number of potentially offending drugs was 2.3, the maximum was 4.5 per subject. Additionally, 89% were at risk for drowsiness, 87% for blurred vision and 67% for confusion. Altogether, diuretics, digitalis and calcium antagonists accounted for 46% of ADR-risks. With regard to DDI, 85% had at least one drug-combination potentially leading to enhanced drug action, 52% had at least one combination potentially leading to reduced action. Most frequently involved in potential DDI were calcium antagonists (20%), digoxin (18%), and thiazides (17%). Most prevalent specific risks due to DDI were postural hypotension (48%), glycoside intoxication (26%), toxic CNS-effects (22%) and hypokalemia (19%). In conclusion, risks for ADR and DDI should be considered carefully and regularly monitored in elderly patients on multimedications. Stopping unnecessary medications, especially with regard to diuretics, digitalis and calcium antagonists, will lead to a marked reduction of the cumulative risks associated with multimedications in old age.