Abstract: OBJECTIVES: The increased risk of adverse events in patients receiving potentially interacting drugs has long been recognized. The purpose of the present study was to evaluate the change in the risk of receiving potentially interacting drugs during a period covering three decades and to examine the relative risk of actual drug combinations. METHODS: The prescriptions from all individuals (about 8,000) with two or more prescriptions during three periods of 15 months, October to December 1983-1984, 1993-1994 and 2003-2004, were collected from an ongoing cohort study in the county of Jämtland, Sweden. The potential interactions were detected by a computerized system. RESULTS: The relative risk (RR) of receiving potentially interacting drugs increased for type C interactions [RR: 1.177, 95% confidence interval (CI): 1.104-1.256] and decreased for type D interactions (RR: 0.714, 95% CI: 0.587-0.868) from the period 1983-1984 to 2003-2004. Polypharmacy for the participants increased by 61%, from 9.05 filled prescriptions per subject in 1983-1984 to 10.6 in 1993-1994 and 14.6 in 2003-2004. The RR was positively correlated to the pronounced increase in polypharmacy; in addition, an exponential relationship was found for the more severe type D interactions. Few interacting drug combinations were responsible for a large proportion of the risk. CONCLUSION: We conclude that the risk of receiving potentially interacting drugs was strongly correlated to the concomitant use of multiple drugs. The pronounced increase in polypharmacy over time implies a growing reason for prescribers and pharmacists to be aware of drug interactions. Recently established national prescription registers should be evaluated for drug interaction vigilance, both clinically and epidemiologically.

Abstract: OBJECTIVE: The widespread use of pharmaceuticals prescribed by different physicians has caused the Swedish government to propose a new legislation with registration of all prescriptions dispensed at the Swedish pharmacies. In the present study, we wanted to examine the frequency, distribution and determinants of potential drug interactions. METHODS: The prescriptions from all individuals (n=8,214) with two or more prescriptions during October 2003 to December 2004 were collected from the ongoing Jämtland cohort study of a total of about 11,000 individuals. Potential drug-drug interactions were detected with a computerized interaction detection system and classified according to clinical relevance (types A-D). RESULTS: On average each individual filled 14.6 (men 14.3, women 14.8) prescriptions during the study period. 3.6% of the individuals used more than 15 different drugs. The number of detected potential drug interactions type A-D was 4,941 (men 1,949, women 2,992). The risk of receiving a potential interaction type A-D was estimated as the cumulative incidence 0.26 (2,116/8,214) overall, 0.22 (748/3,467) for men and 0.29 (1,368/4,747) for women during the 15-month study period. The age adjusted risk, RR(adj), for women was estimated as 1.30. Excluding sex hormones and modulators of the genital system, the RR(adj) was 0.96, with no elevated risk for women. For potential interactions type D, that might have serious clinical consequences, 167 (cumulative incidence 0.0203) individuals (72 men, cumulative incidence 0.0208, 95 women cumulative incidence 0.0200) were detected. The risk of receiving a combination of potentially interacting drugs was positively correlated to age and polypharmacy. The cumulative incidence for elderly was estimated as 0.36 (65-84 years) and 0.39 (85 years and above). The relative risk for individuals with 15 drugs or more was estimated as 3.67 (95% CI 3.46-3.90). CONCLUSION: In a general population there were relatively few severe potential drug interactions. The new Swedish national pharmacy register will provide health care professionals with a powerful tool to systematically review all prescriptions. An alert system should focus on the more potential drug interactions, type C-D, with close monitoring of elderly and patients with polypharmacy.