Exposure to potential drug interactions in primary health care

Harmful drug interactions may occur if one drug alters the effect of another drug. During the course of one year, about one-third of the population are exposed to the concurrent use of two or more drugs (polypharmacy). On average, 15% of individuals with polypharmacy are exposed to drugs carrying a risk of potential interactions. Elderly patients exposed to polypharmacy are at highest risk and should therefore be kept under intensified monitoring. Objective - To analyse the prevalence of potential drug interactions, and to identify patients particularly prone to drug interaction. Design - Database study (Odense University Pharmacoepidemiologic Database). Setting - Individuals exposed to polypharmacy in 1999 were examined for potential drug interactions. Subjects - Inhabitants of the County of Funen (n=471 &#116 732). Main outcome measures - Prevalence of potential drug interactions. Results - One-third of the population were exposed to polypharmacy and among these 15% were exposed to drugs carrying a risk of harmful interaction. Among the elderly with polypharmacy, 25% aged 60-79 years and 36% over 80 years received drugs carrying the risk of interaction. Among individuals exposed to potential drug interaction, 62% were exposed only to one drug interaction and 38% to two or more different drug interactions. The drugs accounting for the highest number of potential interactions were diuretics, NSAIDs, ACE-inhibitors, digoxin, oral antidiabetics, calcium channel blockers, anticoagulants and beta-blockers. When focusing only on major drug interactions, potassium-sparing diuretics and oral anticoagulants were the most frequently involved drugs. Conclusion - Elderly patients exposed to polypharmacy should be kept under intensified monitoring as they are at increased risk of clinically significant drug interactions.     

Drug interactions in Brazilian type 2 diabetes patients

The aim of this paper is to identify the prevalence of the most frequent drug interactions in patients using oral antidiabéticos and their association with capillary glucose and medication adherence. In total, 579 type 2 diabetes mellitus patients from 12 health institutions in Fortaleza, Brazil were interviewed in 2009. A form was applied, including questions on medication use, comorbidities, lifestyle, body mass index and random capillary glucose. Results revealed that 26.7% used five or more different drugs simultaneously and daily. Statistically significant drug interactions occurred between antidiabéticos and diuretics, angiotensin‐converting enzyme inhibitors, anti‐lipidaemics and corticoids. No significant association was found between polypharmacy, medication adherence and glucose. It is important for nurses, in consensus with other health professionals, to consider the possibility of other drugs that mean less risk for diabetes patients’ glucose control or of increased antidiabetics doses.     

Analysis of the association between polypharmacy and socioeconomic position among elderly aged > or =77 years in Sweden

Background: Polypharmacy is an important patient safety concern and has been associated with increased adverse drug reactions, hospitalization, and mortality in the elderly. However, few studies have analyzed the association between socioeconomic position (SEP) and the extent of drug use in older people. Objectives: The aims of this study were to investigate the prevalence of polypharmacy and the association between polypharmacy and SEP, as measured by education, occupation, and income. Methods: For this cross-sectional study, data from a nationally representative sample (Swedish Panel Study of Living Conditions of the Oldest Old [SWEOLD] 2002) aged >/=77 years were analyzed (n = 621). Information on drug use was based on personal interviews, and polypharmacy was defined as concurrent use of >/=5 drugs. Other measurements included were age, sex, education, occupation, income, comorbidity, marital status, and living situation. The association between polypharmacy and SEP was assessed by logistic regression. Results: The mean number of drugs used in the sample was 4.4; in less educated patients, 4.6; more educated, 4.0. Polypharmacy was observed in 42.2% of the elderly. Overall, antithrombotic agents (42.5%), P-blocking agents (28.3%), and high-ceiling diuretics (28.0%) were the most prevalent drugs. Low education was associated with polypharmacy (odd ratio [OR], 1.46; 95% CI, 1.02-2.07), after controlling for age and sex. However, the association between low education level and polypharmacy was not significant after adjustment for age, sex, comorbidity, marital status, and living situation (OR, 1.39; 95% CI, 0.95-2.04). Moreover, we did not observe any association between occupation or income and polypharmacy. Conclusions: The results from this study suggest that >40% of people aged >/=77 years in Sweden are exposed to polypharmacy, defined as the use of >/=5 drugs. There was a higher prevalence of polypharmacy among elderly with low education. However, after controlling for comorbidity, martial status, and living situation, polypharmacy was not related to low education. Further studies in larger populations are needed to elucidate the association between SEP and drug use.     

Is there a need for an alternative in the era of novel anticoagulants?

With the development of the new direct oral anticoagulants, many of the unmet needs of the vitamin K antagonists were fulfilled, such as the absence of dietary interactions, few drug interactions, predictable effects and no need for monitoring. However, growing experience with the direct oral anticoagulants indicates there is still room for improvement. Developing antithrombotic agents that optimize their antithrombotic effect while producing little or no risk of bleeding is a long sought after goal. This and other enhanced attributes of candidate drugs are on the horizon.     

Drug interactions in primary care: impact of a new algorithm on risk determination

BACKGROUND: If managed adequately, many drug interactions do not result in clinical manifestations. Earlier studies may have overestimated the risk arising from drug interactions because they usually reported interaction frequencies and the severity of potential outcomes irrespective of their manageability. OBJECTIVE: Our objective was to estimate the risk associated with drug interactions in a large population when not only the severity of possible clinical events but also measures of their prevention (manageability, modulating factors) are considered. METHODS: We evaluated all drug pairs concurrently prescribed to 9481 adults aged 50 to 75 years who participated in a health-screening examination. Drug interactions were evaluated by use of an algorithm with 4 decision layers (severity, manageability, risk/benefit assessment, and patient-related risk factors), and this risk evaluation was compared with the conventional evaluation solely on the basis of severity. RESULTS: More than 52% of the patients received combination therapy. Interaction information was available in a standard source (DRUGDEX; Thomson MICROMEDEX, Greenwood Village, Colo) for only 1029 of all 13,672 individual prescribed drug pairs. Of the drug pairs, 881 (6.4%) were identified as interacting. Of these 881 interactions, 132 (15.0%) were of major severity but 101 of 132 (76.5%) were considered manageable. Only 31 (23.5%) of 132 major interactions (ie, 31/881 [3.5% of all interacting pairs]) offered no management options and should thus be avoided. CONCLUSION: For many commonly prescribed drug pairs, explicit drug interaction information is currently not available in DRUGDEX. For major interactions with published evidence, the overwhelming majority were manageable, and therefore risk estimates only based on the severity of potential outcomes will grossly overestimate the risk associated with such combinations.     

Drug adherence in patients taking oral anticoagulation therapy

Oral anticoagulation has proven to reduce mortality and morbidity of thromboembolic events. One of the most important determinants of the effectiveness and safety of anticoagulation therapy is the adherence to the prescribed therapy. Vitamin K antagonists are characterized by under-utilization, a narrow therapeutic window and multiple food and drug interactions which contribute to a variable dose–response relationship with the risk of insufficient protection and/or increased bleeding risk. The “new” direct oral anticoagulants have demonstrated equal or superior protection and reduced bleeding risks compared to warfarin and are easier to use because of fixed dosing without monitoring of anticoagulation. Controlling of adherence to the direct oral anticoagulants is difficult. Therefore, continuous and regular medication intake represents a pre-requisite for achieving optimal protection. The present review aims to give an overview about the factors that affect drug adherence in patients taking oral anticoagulation drugs and discusses strategies to improve drug adherence.     

Drug and dietary interactions of the new and emerging oral anticoagulants

Oral warfarin is associated with extensive food and drug interactions, and there is a need to consider such interactions with the new oral anticoagulants (OACs) dabigatran etexilate, rivaroxaban and apixaban. A literature survey was conducted using PubMed, EMBASE and recent abstracts from thrombosis meetings to identify publications related to food, drug and dietary supplement interaction studies with dabigatran etexilate, rivaroxaban and apixaban. Clinical experience regarding food interactions is currently limited. Regarding drug–drug interactions, dabigatran requires caution when used in combination with strong inhibitors or inducers of P‐glycoprotein, such as amiodarone or rifampicin. Rivaroxaban (and possibly apixaban) is contraindicated in combination with drugs that strongly inhibit both cytochrome P450 3A4 and P‐glycoprotein, such as azole antimycotics, and caution is required when used in combination with strong inhibitors of only one of these pathways. Important drug interactions of the new OACs that can lead to adverse clinical reactions may also occur with non‐steroidal anti‐inflammatory drugs and antiplatelet drugs, such as aspirin and clopidogrel. Over‐the‐counter (OTC) medications and food supplements (e.g. St. John’s Wort) may also interact with the new OACs. Given the common long‐term use of drugs for some chronic disorders, the frequent use of OTC medications and the need for multiple treatments in special populations, such as the elderly people, it is essential that the issue of drug interactions is properly evaluated. New OACs offer significant potential advantages to the field of venous thromboprophylaxis, but we should not fail to appreciate their lack of extensive clinical experience.     

Drug-drug and drug-disease interactions in the ED: Analysis of a high-risk population

A study was undertaken to determine the potential for adverse drug interactions (ADIs) and drug-disease interactions (DDIs) in a high-risk population of emergency department (ED) patients and to characterize drug-drug and drug-disease interactions in terms of percentage of patients at risk from existing drug regimens, percentage of patients at risk from ED treatment, relation between number of drugs and potential for interactions, types of drugs and diseases posing greatest potential for interaction, and the differences in a general versus community hospital population with respect to these parameters. Records of 205 consecutive patients, 111 from a general hospital teaching facility ED (Facility 1) and 94 from a community hospital ED (Facility 2) were retrospectively reviewed. The records of all patients receiving three or more medications and all patients older than 50 years of age receiving two or more medications were analyzed by two computer programs for the presence of potential drug-drug and drug-disease interactions. A total of 226 potential ADIs were found in 89 patients (47%), with 50% of ADIs being related to ED treatment. A total of 94 potential DDIs were found in 44 patients (21%), with 34% of DDIs being related to ED treatment. The risk of an ADI rose from 13% for patients taking 2 medications to 82% for patients taking 7 or more medications. Eleven medications and four disease categories were identified as having particular potential for interactions. No significant differences were found between the general and the community hospital populations in these respects. ED patients taking three or more medications and patients older than 50 years of age taking two or more medications are at substantial risk for adverse drug-drug and drug-disease interactions. The risk is increased in patients taking particular drugs or having particular disease states.     

Polypharmacy with common diseases in hospitalized elderly patients

BackgroundElderly persons are exposed to polypharmacy because of multiple chronic conditions. Many risk factors for polypharmacy have been identified including age, race/ethnicity, sex, educational achievement level, health status, and number of chronic diseases. However, drugs prescribed for individual diseases have not been analyzed.ObjectiveThe objective of this study was to analyze each common disease in the elderly with respect to prescribed drugs and polypharmacy.MethodsA 1-year (January through December 2009) cross-sectional study was performed in which all drugs given to hospitalized elderly patients (age, >65 years) were investigated. Common diseases of the elderly were separated into disease groups including hypertension, hyperlipidemia, gastric ulcer, previous stroke, reflux esophagitis, diabetes mellitus, malignancy, osteoporosis, angina pectoris, congestive heart failure, chronic obstructive pulmonary disease, dementia, and depression.ResultsAmong 1768 elderly patients, the mean (range) age of study patients was 78 (65 to 100) years. The mean (SD) number of diseases was 7.7 (3.4), and the number of drugs overall was 4.9 (3.6). The number of drugs and prevalence of polypharmacy were hypertension, 5.2 (3.9 [51%]); hyperlipidemia, 5.6 (3.8 [58%]); gastric ulcer, 5.4 (3.8 [53%]); previous stroke, 5.8 (3.2 [61%]); reflux esophagitis, 5.6 (3.8 [40%]), diabetes mellitus, 5.6 (3.1 [54%]); malignancy, 4.1 (3.1 [37%]); osteoporosis, 5.4 (3.4 [45%]); angina pectoris, 5.7 (3.6 [42%]); congestive heart failure, 6.1 (4.0 [60%]); chronic obstructive pulmonary disease, 5.0 (3.5 [53%]); dementia, 5.1 (3.2 [52%]); and depression, 7.0 (4.2 [73%]).ConclusionsWhen assessing the risk of polypharmacy, physicians should carefully consider the type of any chronic disease. Elderly patients with multiple diseases may be subjected to further polypharmacy.     

New oral anticoagulants: are coagulation units still required?

Chronic antithrombotic therapy involves the use of anticoagulants, antiplatelets given either as monotherapy or in combination for the prevention of thrombotic complications. The most feared and sometimes fatal complication with this therapy is bleeding. It should be considered a “golden rule” that a drug or combination of drugs that maximizes efficiency (decreased thromboembolic risk) will probably be less safe (increased risk of bleeding), and this holds true either for single therapy or during combined therapy. The chances of bleeding indicated by risk tables can be useful but show only a snapshot, and the biological, social, environmental, and drug changes and therapeutic adherence also determine changes in the risk of thrombosis and bleeding. Bleeding is an eventuality that occurs in places of “locus minoris resistentiae,” and the results of careful phase 3 studies thus cannot be completely predictive of outcomes when a medication is introduced on the pharmaceutical market. With the use of warfarin, the International Normalized Ratio (INR) that has been established to indicate adequately balanced therapy is between 2.0 and 3.0. With the new oral anticoagulants, the pharmaceutical companies emphasize that it is not necessary to monitor anticoagulant effects. In studies with different doses of new oral anticoagulants, however, incidence of clinically significant bleeding complications have been directly related to the doses. Therefore, therapeutic excesses can condition bleeding risk and therapeutic limitation can increase thrombotic risk, especially when short-acting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants, setting levels of safety and effectiveness through periodic dosage and monitoring of their anticoagulant effects. Therefore, we still recommend the use of anticoagulation units for monitoring during treatment with the new oral anticoagulants.