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Background: Despite the availability and daily use of computerized drug-drug interaction surveillance systems, exposure to potentially relevant drug-drug interactions (DDIs) continues. DDI management guidelines are often inadequate and clear management options are lacking, which attributes to overriding of DDI signals. Although general criteria for the development and reporting of high-quality clinical practice guidelines have been identified, it appears these have not yet been applied to DDI management guidelines.Objectives: The aim of the study was to assess the clarity and applicability of guidelines for the management of potentially harmful DDIs.Methods: We selected 13 DDIs that are potentially harmful for patients and frequently occur in community pharmacy practice in the Netherlands. The clarity and applicability of the management guidelines of these DDIs were appraised using the appropriate two domains - 'Clarity and presentation' and 'Applicability', of the validated Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument. The appraisal was performed by 12 community pharmacists and 12 general practitioners. The standardized domain scores and mean item scores for 'Clarity and presentation' and 'Applicability' were compared.Results: All DDI management guidelines were generally found to score well on 'Clarity and presentation', but poorly with respect to 'Applicability' (standardized domain scores 68.0 vs 26.1%). Within the domain 'Clarity and presentation', the item 'tools for application' received the lowest scores. Within the domain 'Applicability', cost implications, organizational barriers and key review criteria were all poorly documented. All guidelines presented non-directive advice using words such as 'consider' and 'regularly'.Conclusions: Developers of DDI management guidelines should take the appropriate domains of the AGREE Instrument into consideration in their development processes. The applicability of DDI management guidelines should be pretested before publishing. To improve guideline quality, more attention should particularly be paid to the available tools for applications and cost implications. [ABSTRACT FROM AUTHOR]

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BACKGROUND: The prevention of drug-drug interactions requires a systematic approach for which the concept of clinical risk management can be used. The objective of our study was to measure the frequency, nature and management of drug-drug interaction alerts as these occur in daily practice of Dutch community pharmacies. METHODS: In total, 63 Dutch pharmacies collected all drug-drug interaction alerts during 153 research days (on average 2.4 days/pharmacy), as well as variables related to these alerts, such as involved medicines, first time or recurrent drug-drug interaction, same or different prescribers, patient data (age, sex) and information about the management of drug-drug interactions by the pharmacy. The latter was discriminated into internal procedures only and external action, such as communication with the patient, the prescriber or the anticoagulation clinic and prescription modification. All drug-drug interactions were classified into categories of clinical relevance (A–F) and available evidence (0–4). RESULTS: A total of 43 129 prescription-only medicines were dispensed during the study period. On average, 16.8 interaction alerts per day per pharmacy were collected. Approximately 6% of all prescriptions generated a drug-drug interaction alert. Of all alerts (n = 2572), 31.1% occurred for the first time and with 21% two different prescribers were involved. The 20 most frequently occurring drug-drug interaction alerts accounted for approximately 76% of all alerts. Cardiovascular drugs, NSAIDs, oral contraceptives and antibacterials were most frequently involved. External action was taken in response to 27.3% of the alerts, meaning either a modification of one of the concerned prescriptions (n = 65; 9.3%), communication with the prescriber or anticoagulation clinic (n = 90; 12.8%) or communication with the patient or a relative (n = 547; 77.9%). Where there was no external action (n = 1860; 72.3%), pharmacists concluded in about two-thirds of cases that the drug-drug interaction had been managed in the past. Other reasons not to intervene externally were for instance: incorrect alert; acceptable drug-drug interaction; or outcome of the interaction considered irrelevant. Adjusted for several variables, a first alert was found to be a main determinant for external action. After stratifying for first alerts no other significant determinants were found. CONCLUSIONS: A high frequency of drug-drug interaction alerts was found. Most concerned recurrent alerts, which were the main reason not to act externally. Concerning the assessment phase in the risk-management process, drug-drug interactions with no or low evidence/relevance should be reconsidered. Concerning the management of drug-drug interactions in pharmacies, the opportunity to actively suppress alerts for a certain period of time should be studied in more detail. There are indicators that the management of patient-orientated advice could be improved and a greater degree of consistency developed for the management of first and recurrent interaction alerts. [ABSTRACT FROM AUTHOR]