Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants: an intervention study in community pharmacies.

INTRODUCTION: Direct oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. METHODS: We conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. RESULTS: In total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. CONCLUSIONS: This study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations.

Rhinitis control and medication use in a real-world sample of patients with persistent rhinitis or rhinosinusitis: a community pharmacy study.

BACKGROUND: Little is known about rhinitis control in real-life, nor about the contribution of treatment-related and patient-related factors. OBJECTIVE: This study aimed to examine the level of rhinitis control and rhinitis medication utilization in patients with persistent rhinitis, and to identify predictors of rhinitis control. METHODS: A cross-sectional observational study was conducted in patients with persistent rhinitis recruited in community pharmacies. Participants completed the Rhinitis Control Assessment Test (RCAT), and a questionnaire on patient/rhinitis characteristics, and rhinitis medication use. A visual analogue scale (VAS) for nasal symptoms was also completed. Pharmacy dispensing data was used to calculate adherence to intranasal glucocorticoids. Nasal spray technique was evaluated using a standardized checklist. Predictors of rhinitis control were explored using a linear regression model. RESULTS: A total of 1514 patients, recruited in 215 pharmacies, participated in the study (mean age 48.7 years, 62% female). Almost 60% exhibited suboptimal rhinitis control (RCAT ≤ 21/30). A 50mm cut-off on the VAS yielded 78.1% sensitivity to identify suboptimal rhinitis control. Participants most frequently used intranasal glucocorticoids (55.6%) and intranasal decongestants (47.4%). Only 10.3% of current nasal spray users demonstrated perfect technique. More than half (54.8%) of glucocorticoid users were identified as underadherent. Female sex, self-reported nasal hyperreactivity, active asthma, and use of oral/intranasal decongestants or nasal saline were identified as predictors of worse rhinitis control. CONCLUSION: Suboptimal rhinitis control was common in this real-life sample of persistent rhinitis patients. Improving use of rhinitis medication may be key to increase disease control.

Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.

PURPOSE: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. RESULTS: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)). CONCLUSION: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.

AIMS: The clinical relevance of common pharmacokinetic interactions with non-vitamin K antagonist oral anticoagulants (NOACs) often remains unclear. Therefore, the impact of P-glycoprotein (P-gp) and CYP3A4 inhibitors and inducers on clinical outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. METHODS AND RESULTS: AF patients were included between 2013 and 2019 using Belgian nationwide data. Concomitant use of P-gp/CYP3A4-interacting drugs at the time of NOAC initiation was identified. Among 193 072 NOAC-treated AF patients, 46 194 (23.9%) and 2903 (1.5%) subjects concomitantly used a P-gp/CYP3A4 inhibitor or inducer, respectively. After multivariable adjustment, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding [adjusted hazard ratio (aHR) 1.24, 95% confidence interval (CI) (1.18-1.30)] and all-cause mortality risks [aHR 1.07, 95% CI (1.02-1.11)], but not with thromboembolism in NOAC-treated AF patients. A significantly increased risk of major bleeding was observed with amiodarone [aHR 1.27, 95% CI (1.21-1.34)], diltiazem [aHR 1.28, 95% CI (1.13-1.46)], verapamil [aHR 1.36, 95% CI (1.03-1.80)], ticagrelor [aHR 1.50, 95% CI (1.20-1.87)], and clarithromycin [aHR 1.55, 95% CI (1.14-2.11)]; and in edoxaban [aHR 1.24, 95% CI (1.06-1.45)], rivaroxaban [aHR 1.25, 95% CI (1.16-1.34)], and apixaban users [aHR 1.27, 95% CI (1.16-1.39)], but not in dabigatran users [aHR 1.07, 95% CI (0.94-1.23)]. Concomitant use of P-gp/CYP3A4 inducers (e.g. antiepileptic drugs like levetiracetam) was associated with a significantly higher stroke risk [aHR 1.31, 95% CI (1.03-1.68)], but not with bleeding or all-cause mortality. CONCLUSION: Concomitant use of P-gp/CYP3A4 inhibitors was associated with higher bleeding and all-cause mortality risks in NOAC users, whereas the use of P-gp/CYP3A4 inducers was associated with higher stroke risks.

Minimal Adherence Threshold to Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation to Reduce the Risk of Thromboembolism and Death: A Nationwide Cohort Study.

PURPOSE: Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effect of NOACs is currently unknown. Therefore, we investigated thresholds of NOAC adherence in association with thromboembolic and mortality risks. METHODS: Patients with AF initiating NOACs between 2013 and 2019 were identified in Belgian nationwide data. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability of treatment weighted Cox regression was used to investigate outcomes. RESULTS: 92,111 persons were included (250,750 person-years). Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and < 80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)). Significantly higher risks of all-cause mortality were observed with decreasing levels of NOAC adherence, which were already higher among NOAC users with a one-year PDC of 90-94% versus 100% (aHR 1.09, 95%CI (1.01-1.17)). Findings were similar with once-daily and twice-daily dosed NOACs. CONCLUSION: Poor adherence to NOACs is associated with increased risks of thromboembolism and all-cause mortality. The minimal adherence threshold should be ≥ 90%, preferably even ≥ 95%.

Investigating Levothyroxine Use and Its Association with Thyroid Health in Patients with Hypothyroidism: A Community Pharmacy Study.

Background: To gain maximum therapeutic effect while minimizing side effects, it is imperative for patients with hypothyroidism to use their levothyroxine (LT4) correctly, such as adhering to the prescribed regimen. Little is currently known about how patients actually use LT4 in real life. We investigated the use of LT4, as well as the thyroid health (thyrotropin [TSH] and health-related quality of life [HR-QoL]), and evaluated if proper LT4 use is associated with better thyroid health. Methods: A cross-sectional observational study was conducted in a Belgian community sample of adults using LT4 for hypothyroidism since ≥2 years. Participants completed a self-administered questionnaire on patient characteristics, self-reported adherence to LT4, timing of intake, and co-medication. They also completed the thyroid-specific patient-reported outcome (ThyPRO-39) questionnaire, measuring the HR-QoL. Pharmacy dispensing data were used to calculate the medication possession ratio (MPR). Results: We included 856 participants (mean age 61.4 ± 14.3 years, 86% [740/856] females). Approximately one in four participants (138/563) had out-of-range TSH levels. Generally, ThyPRO-39 scores were in the lower part of the range (indicating better HR-QoL), with the scales "emotional susceptibility" and "tiredness" showing the worst scores. Approximately 28% (178/632) of the participants were classified as non-adherent (MPR <80%), corresponding to at least 73 cumulative days per year without LT4 intake. Twenty-five percent (212/854) of participants self-reported non-adherence, with unintentional non-adherence (forgetfulness) most frequently reported (21.9%, 187/854). Only 39% (329/836) of participants complied with the recommendation of ingesting LT4 ≥ 30 minutes before eating. Additionally, 7% (58/856) of participants concurrently used molecules that bind to LT4, without applying the recommended dosing interval. There was no significant correlation between LT4 usage (adherence, timing of intake, and interaction with complex forming drugs) and TSH or HR-QoL. Conclusions: We found that many participants with hypothyroidism did not use their LT4 as effectively as possible, particularly with respect to timing of administration. However, the participants' HR-QoL seemed largely satisfactory, and there was no significant correlation between correctly using LT4 and thyroid health.

Drug-drug interactions with direct oral anticoagulants: development of a consensus list for ambulatory care.

BACKGROUND: Direct oral anticoagulants (DOACs) can be involved in clinical relevant drug-drug interactions (DDIs) which may compromise safe and effective use. However, assessing the clinical relevance of DDIs with DOACs and managing these interactions optimally, can be challenging in clinical practice. AIM: To develop a practice-oriented list of potentially clinically relevant DDIs with DOACs with corresponding management plans for which it is important to screen in ambulatory care. METHOD: The RAND/UCLA appropriateness method was used to develop the DOACs DDI list. In a first step a preliminary list was compiled of potentially clinically relevant DDIs per DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) using five reference sources. Subsequently, a two-step modified Delphi process involving a multidisciplinary panel (n = 10) including both pharmacists and physicians with expertise in all decision-making disciplines involved in care for patients using DOACs and with diversity of practice setting, was used to reach expert agreement on a final list of DDIs with corresponding management plans. RESULTS: After a two-step consensus round, 71 DDIs for 20 different interacting drugs were included: five pharmacodynamic, nine pharmacokinetic inhibitor and six pharmacokinetic inducer interacting drugs. Considerations raised and discussed by the panellists were related to (1) the necessity of the interacting drug, (2) the manageability of the DDI (whether there are any alternatives), (3) the (clinical) evidence-base for the DDI and (4) the (potential) consequences of the DDI. CONCLUSION: We developed a consensus list with specific and straightforward management plans on potentially clinically relevant DDIs with DOACs, for use in ambulatory care.

Trends in oral anticoagulant use in patients with atrial fibrillation in Belgium from 2013 to 2019: A nationwide cohort study.

AIM: Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, sex and physician's specialty may be present. Therefore, incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC were investigated. METHODS: Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between 2013 and 2019 were identified. OAC use was investigated per half-year. Factors influencing NOAC vs. VKA initiation were identified by multivariable logistic regression. RESULTS: Among 448 661 included OAC-treated AF patients, 297 818 were newly treated. Incident OAC use ranged from 45-49 to 42-44 users/10 000 persons between 2013 and 2019, whereas prevalent OAC use increased from 337 to 435 users/10 000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015, respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (25.3% vs. 33.0% between 2013 and 2019) and female subjects had 5% significantly lower odds of NOAC vs. VKA initiation than men. CONCLUSION: Since 2013, prevalent anticoagulant use increased almost one third in Belgium, while incident use was stable. Potential (N)OAC underuse in women requires further exploration.

The Indispensable Nasal Decongestant: Patients' Views and Perspectives on Nasal Decongestant Overuse.

BACKGROUND: Rhinitis medicamentosa (RM) is a type of nonallergic rhinitis caused by prolonged use of nasal decongestants (NDs). Although it is a preventable phenotype of rhinitis, little is known about patients dealing with this condition. OBJECTIVE: To gain a better understanding of patients' views and experiences of ND overuse, and potential facilitators and barriers to discontinue the overuse. METHODS: We performed a qualitative study using in-depth semistructured interviews with 22 patients who have been using an ND on an almost daily basis for at least 6 months. The interviews were conducted face-to-face, audio-recorded, and transcribed verbatim. Data analysis followed the grounded theory approach. RESULTS: Interviewees described the large impact of nasal congestion on their daily lives. Despite efforts to try other treatment options, the ND was considered the only effective aid to resolve the troublesome symptom. Most participants were aware that the prolonged use was problematic, sometimes leading to hiding behavior in order to avoid criticism by others including their health professionals. Many participants expressed a strong will to discontinue. However, multiple barriers to withdrawal were identified including fear of surgery or the impact of withdrawal on sleep, lack of good alternatives, and negative experiences with past withdrawal attempts. Patients thus face a dilemma in which the barriers to withdrawal currently outweigh the possible benefits. CONCLUSION: The use of NDs is considered indispensable by many chronic users. The facilitators and barriers identified in this study provide opportunities to reduce the use of NDs and the prevalence of RM in the future.

Adherence and persistence to oral anticoagulants in patients with atrial fibrillation: A Belgian nationwide cohort study.

Background: Since non-vitamin K antagonist oral anticoagulants (NOACs) do not require coagulation monitoring, concerns of lower adherence and persistence to NOACs than vitamin K antagonists (VKAs) have been raised. Moreover, little is known on the frequency of permanent cessation and switching between anticoagulants in patients with atrial fibrillation (AF). Therefore, persistence, reinitiation, switching and adherence to oral anticoagulants (OACs) were investigated. Materials and methods: AF patients with a first OAC prescription claim between 2013 and 2019 were identified in Belgian nationwide data. Persistence, reinitiation and switching were estimated using Kaplan-Meier analyses. Adherence was investigated using the proportion of days covered (PDC). Predictors for non-adherence and non-persistence were identified by multivariable logistic regression. Results: Among 277,782 AF patients, 69.6% NOAC and 37.2% VKA users were persistent after 1 year, whereas 44.3% and 18.9% after 5 years, respectively. After one year, 67.1% rivaroxaban, 68.1% dabigatran, 69.8% apixaban, and 76.9% edoxaban users were persistent. Among subjects having discontinued NOAC or VKA treatment, 75.4% and 46.1% reinitiated any OAC within 5 years, respectively. VKAs were more frequently switched to NOACs than vice versa (17.6% versus 2.5% after 1 year). After 1 year, a high PDC (≥ 90%) was observed in 87.8% apixaban, 88.6% dabigatran, 91.3% rivaroxaban, and 94.7% edoxaban users (90.2% NOAC users). Adherence and persistence were higher in older, female subjects, while lower in subjects with dementia or hyperpolypharmacy. Conclusion: Adherence and persistence to NOACs were high. However, 10% of subjects were non-adherent after 1 year and one-fourth did not reinitiate anticoagulation within 5 years after NOAC discontinuation.

Prevalence and management of drug interactions between nonsteroidal anti-inflammatory drugs and antithrombotics in ambulatory care.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents is associated with increased risks of both bleeding and thromboembolism. In this prospective intervention study, community pharmacists screened for NSAID-antithrombotic interactions and contacted the prescribing physician to discuss interaction management. We included 782 interactions; these were found in an older, polymedicated patient population (mean age: 68 y, median of 5 other drugs). Ibuprofen (in 43.0% of cases) and low-dose aspirin (78.8%) were the most frequently involved NSAID and antithrombotic, respectively. Anticoagulants were involved in 16.1% of interaction cases. For 61% of cases, the interacting drugs were prescribed by the same physician. The pharmacist-physician discussion about how to manage the interaction mostly resulted in no change of pharmacotherapy (60.7%); the most frequent reason given by physicians was that the NSAID was for short-term use only. In 39.3% of cases the discussion resulted in a pharmacotherapy change; replacing the NSAID by paracetamol was the most common change.

Community pharmacist counseling improves adherence and asthma control: a nationwide study.

BACKGROUND: Pharmaceutical counseling (PC) interventions have been shown to improve adherence to controller medication and asthma control. However, the real-life impact of these PC interventions in difficult-to-control asthma patients remains unclear. We aimed to assess the effectiveness of PC interventions in real life using nationwide claims data. METHODS: Demographics and drugs use of patients who received ICS in 2017 with or without pharmaceutical counseling were retrieved from a Belgian claims database. Asthma-related drug use from 1 year before first ICS dispensing in 2017 (reference period) was compared with 1 year after. Outcomes were usage of inhaled corticosteroids (ICS) in defined daily doses (DDD), proportion of users of short-acting beta-agonist (SABA), antibiotics, oral corticosteroids (OCS), asthma biologicals and controller-to-total (CTT) ratio. RESULTS: The study population consisted of difficult-to-control asthma patients aged 5-40 years with at least the first interview within 90 days after first ICS dispensing (n = 1350). ICS usage increased significantly in the year after PC intervention compared with the reference period (+ 43.3 DDD/patient, p < 0.05). A nominal decrease was observed in the proportion of SABA (48.0 to 46.2%) and antibiotics (54.5 to 52.7%) after PC intervention compared with the reference period. CTT ratio significantly increased from 0.671 to 0.749 (p < 0.05). The proportion of biological users was nominally lower in the intervention group compared with a control group (n = 50,477) in the post-intervention time period (0.22% versus 0.30%). CONCLUSIONS: This first nationwide study among difficult-to-control asthma patients suggests that community pharmacist counseling is effective in real life to improve controller adherence and asthma control.

Physicians' and pharmacists' views and experiences regarding use of direct oral anticoagulants in clinical practice.

AIM: Direct oral anticoagulants (DOACs) are increasingly used compared to vitamin K antagonists (VKAs). Guidelines advocate a structured multidisciplinary approach in the management of patients treated with DOACs. The aim of this study was to assess the views and experiences of physicians and pharmacists regarding DOAC use in clinical practice. METHODS: An online questionnaire was sent to both primary (general practitioners [GPs], community pharmacists) and secondary healthcare professionals (cardiologists, residents in internal medicine and hospital pharmacists) between March and July 2020. The questionnaire covered four topics: (i) current practice, (ii) prescribing behaviour (only for physicians), (iii) self-perceived knowledge about DOACs and (iv) views and opinions about DOACs versus VKAs. RESULTS: In total, 110 physicians and 111 pharmacists completed the survey. Healthcare professionals in secondary care had more experience with DOACs and felt more confident with higher self-perceived knowledge about DOACs compared to their colleagues in primary care. Healthcare professionals' self-perceived knowledge was more or less complementary, for example physicians felt less confident in managing drug-drug interactions (DDIs) where pharmacists reported being more confident in this topic. Physicians reported uncertainties on the potential impact of risk factors - such as older age, lower body weight and DDIs - on appropriate DOAC dosing. CONCLUSION: Complementarity in physicians' and pharmacists' self-perceived knowledge levels of DOACs may facilitate and necessitate future multidisciplinary collaboration initiatives for the management and follow-up of DOAC patients.

The implementation of risk minimization measures to prevent teratogenic pregnancy outcomes related to oral retinoid and valproate use in Belgium.

INTRODUCTION: Both oral retinoid and valproate containing medicines are highly teratogenic. Their use by women of childbearing age is controlled by risk minimization measures (RMMs) introduced by the European Medicine Agency, including the pregnancy prevention programme (PPP). In 2018, the RMMs were revised as previous measures were insufficient to prevent the use of these medicines during pregnancies. AIM & METHODS: A cross-sectional survey was conducted among patients, physicians and pharmacists to evaluate the implementation of the revised RMMs in Belgium. The primary outcome was compliance with key aspects of the PPP. Differences in compliance between oral retinoid and valproate stakeholders were investigated. The relationship between potential determinants (population characteristics and RMM usage) and compliance was studied via multiple logistic regression. RESULTS: A total of 317 eligible patients, physicians and pharmacists participated. The majority of the studied patients fail to comply with the PPP, mainly driven by poor implementation of pregnancy testing. A large number of healthcare providers is unaware of the available educational materials. CONCLUSION: It is likely that a substantial part of Belgian women of childbearing age using oral retinoids or valproate insufficiently meet the PPP requirements. We propose to better inform healthcare providers about the mandatory PPPs and available educational materials as well as to support them with the implementation of such programmes to improve the safe use of these teratogenic medicines.

Prevalence of alcohol-drug interactions in community-dwelling older patients with polypharmacy.

OBJECTIVES: Alcohol and medication use are increasingly prevalent in the older population. Concurrent use of alcohol and alcohol-interactive (AI) medication can lead to significant adverse consequences. METHODS: Three reference works were used to create an explicit list of drug substances for which information about the interaction with alcohol was available in at least one of them. Additional information was extracted from the Summary of Product Characteristics (SPC). The first aim was to generate a list of 256 substances with standardized advice regarding the concurrent use of each drug with alcohol. The second aim was to observe the prevalence of potential drug-alcohol-interactions. The list was applied to a database containing information about alcohol and medication use of 1,016 community-dwelling older patients (≥70 years) with polypharmacy. RESULTS: About half of the sample population reported to consume alcohol at least once a week. Around 22% were classified as frequent drinkers (5-7 days/week) and 11% as heavier drinkers (>7 units/week). Ninety-three percent alcohol consumers in our sample took at least one chronic drug that potentially interacts with alcohol and 42% used at least one chronic drug for which alcohol use is considered contraindicated. CONCLUSIONS: We developed an explicit list of potentially drug-alcohol-interactions in older adults, with standardized handling advice. We observed that prevalence of potential drug-alcohol-interactions is substantial in community-dwelling older patients with polypharmacy.

Prevalence of alcohol-drug interactions in community-dwelling older patients with polypharmacy.

OBJECTIVES: Alcohol and medication use are increasingly prevalent in the older population. Concurrent use of alcohol and alcohol-interactive (AI) medication can lead to significant adverse consequences. METHODS: Three reference works were used to create an explicit list of drug substances for which information about the interaction with alcohol was available in at least one of them. Additional information was extracted from the Summary of Product Characteristics (SPC). The first aim was to generate a list of 256 substances with standardized advice regarding the concurrent use of each drug with alcohol. The second aim was to observe the prevalence of potential drug-alcohol-interactions. The list was applied to a database containing information about alcohol and medication use of 1,016 community-dwelling older patients (≥70 years) with polypharmacy. RESULTS: About half of the sample population reported to consume alcohol at least once a week. Around 22% were classified as frequent drinkers (5-7 days/week) and 11% as heavier drinkers (>7 units/week). Ninety-three percent alcohol consumers in our sample took at least one chronic drug that potentially interacts with alcohol and 42% used at least one chronic drug for which alcohol use is considered contraindicated. CONCLUSIONS: We developed an explicit list of potentially drug-alcohol-interactions in older adults, with standardized handling advice. We observed that prevalence of potential drug-alcohol-interactions is substantial in community-dwelling older patients with polypharmacy.

Ghent Older People's Prescriptions Community Pharmacy Screening (GheOP3S)-Tool Version 2: Update of a Tool to Detect Drug-Related Problems in Older People in Primary Care.

BACKGROUND: The Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S)-tool was developed in 2016 as a screening tool to detect drug-related problems (DRPs) and to help in performing medication reviews in older people (≥ 65 years). OBJECTIVE: This study aimed to revise and update the GheOP3S-tool. METHODS: Users' comments were collected to improve the usability and appropriateness of the original GheOP3S-tool, followed by a two-round modified Delphi process according to the RAND/UCLA appropriateness method. This included a literature review, a round zero meeting, a first written round (with 15 international and multidisciplinary experts) and a second face-to-face round (with 11 experts) to change, delete or add GheOP3S-criteria. An additional third round with 14 community pharmacists was organised to preserve criteria applicable in the current community pharmacy practice. RESULTS: The updated GheOP3S-tool consists of five lists of DRPs and a new addendum containing medications that should be avoided or used with caution in older people with reduced renal function. During the first two rounds, related criteria were grouped, 14 criteria were added and 17 criteria were deleted from the original tool. All criteria were deemed applicable in round 3. This led to a final tool (version 2) with 64 GheOP3S-criteria. CONCLUSION: GheOP3S-criteria were revised and updated according to experts' agreement on their clinical relevance and recent scientific evidence. Future studies should investigate the impact of pharmacist-led medication reviews with GheOP3S-tool version 2 on clinical, humanistic and economic outcomes in primary care.

Appropriateness of direct oral anticoagulant dosing in patients with atrial fibrillation according to the drug labelling and the EHRA Practical Guide.

BACKGROUND: This study aimed to evaluate the prevalence of potential drug-drug interactions (DDIs) and the appropriateness of direct oral anticoagulant (DOAC) dosing according to both the Summary of Product Characteristics (SmPC) and the European Heart Rhythm Association (EHRA) Practical Guide in a 'real-world' sample of non-valvular atrial fibrillation (NVAF) patients. METHODS AND RESULTS: Data of a cross-sectional observational study in a primary care sample of 654 long-term DOAC users were used for this sub-analysis. A total of 262 potential DDIs were identified in 220 patients (33.6%). Pharmacodynamic DDIs were present in 163 patients (24.9%) and pharmacokinetic DDIs in 82 patients (12.5%). One-third of patients (33.8%) received reduced DOAC dose. According to the dosing recommendations in the SmPC, 81.7% of DOACs were dosed appropriately. According to the EHRA recommendations, 76.6% of DOACs were dosed appropriately. Dosing recommendations were consistent for 90.7% of patients, with both the SmPC and EHRA Practical Guide considering DOACs dosed appropriately in 74.5% of patients, overdosed in 7.8%, underdosed in 7.6% and contraindicated in 0.8%. However, for the remaining 9.3% dosing recommendations differed between SmPC and EHRA. CONCLUSIONS: This 'real-world' analysis of DOAC dosing demonstrated that in about one-third of NVAF patients potential DDIs were present. In 18.3% and 23.4% of patients, DOACs were dosed inappropriately according to the SmPC and EHRA Practical Guide respectively. In almost 10% of the study population dosing advice was inconsistent between both references. More research is needed to ensure appropriate DOAC dosing in this 'grey zone' population.

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants.

OBJECTIVE: This study aimed to assess implementation adherence (how well the patient's actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with and beliefs about NOACs in a real-world sample of long-term NOAC users. METHODS: A cross-sectional observational study was conducted in home-dwelling adults who started taking a NOAC at least 1 year prior to inclusion. Pharmacy dispensing data were used to calculate the Medication Possession Ratio (MPR). Patients were recruited in 158 community pharmacies in Flanders, Belgium. They completed a questionnaire collecting basic characteristics and exploring self-reported adherence to NOACs (using the Medication Adherence Report Scale, MARS) and experiences with and beliefs about NOACs (using the Beliefs about Medicines Questionnaire, BMQ). RESULTS: A total of 766 patients (mean age 76.2±8.8 years, median CHA2DS2-VASc score 4 (IQR=3-4)) were included. The majority (93.5%) used NOAC for stroke prevention in atrial fibrillation. The median MPR was 95.2% (IQR=87.8-99.7) which corresponds with half of the study population not taking their NOAC on at least 17 cumulative days per year. Almost 21% of participants reported non-adherence on the MARS (score <25), with unintentional non-adherence (forgetfulness) most frequently reported (15.4%). Although two-thirds of NOAC users indicated to experience adverse drug reactions, the BMQ demonstrated a positive attitude towards NOAC therapy, where necessity beliefs outweigh the concerns. CONCLUSIONS: Our data indicate that long-term NOAC users have high implementation adherence and a positive attitude towards NOAC therapy. However, taking into account patients' thromboembolic risk and NOACs' short half-lives, further optimisation of NOAC use seems warranted in this population.