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.

Self-Management of Medication on a Cardiology Ward: Feasibility and Safety of the SelfMED Intervention.

An intervention, SelfMED, was introduced to facilitate patient self-management of medication during hospitalization. This study aimed to evaluate the feasibility and safety of the SelfMED intervention. All patients in a cardiology ward in a Belgian regional hospital were assessed for suitability for inclusion, applying an evidence-based stepped assessment tool. Patients eligible for medication self-management and willing to participate were included in the study (i.e., consecutive sampling). Patients who self-managed their medication were closely monitored by nurses. The feasibility of medication self-management was evaluated by implementation and completion rates and the opinions of cardiologists. Safety was evaluated by medication administration errors and errors in patients' registration of intake. Of 159 patients assessed for eligibility to self-manage medication in-hospital, 61 were included. A total of 367 medicines were self-managed. Pill counts showed 3 administration errors (0.8%), and on 6 occasions (1.7%) the patient's registration of the intake was incorrect. SelfMED was deemed feasible within the hospital ward. In cardiologists' opinions, SelfMED requires substantial time investment. In summary, SelfMED facilitated patient medication self-management in-hospital. As an essential step in the preparation for a full trial, this study showed it is feasible and safe to implement the intervention and identified some possibilities for refinement.

Management of allergic rhinitis symptoms in the pharmacy Pocket guide 2022.

Background: Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication-related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods: Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence-based, integrated care approach. Results: This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence-based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion: This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.

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.

Impact of P-glycoprotein and/or CYP3A4-interacting drugs on effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: A meta-analysis.

AIMS: P-glycoprotein (P-gp) and CYP3A4-interacting drugs influence plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs). However, the clinical relevance is questioned. Therefore, the impact of pharmacokinetically-interacting drugs on the effectiveness and safety of NOACs in patients with atrial fibrillation (AF) was investigated. METHODS: A meta-analysis was performed based on randomized controlled trials and observational studies retrieved from Pubmed and Embase that investigated the impact of concomitantly used P-gp/CYP3A4-interacting drugs on the risk-benefit profile of NOACs in AF patients. RESULTS: Fifteen studies were included, investigating 21 711 and 306 421 NOAC-treated AF patients with and without P-gp/CYP3A4 inhibitor use respectively, while only 1 study included P-gp/CYP3A4 inducers. In NOAC-treated AF patients, concomitant use of P-gp/CYP3A4 inhibitors was associated with significantly higher major bleeding (relative risk [RR] 1.10, 95% confidence interval [CI; 1.01-1.19]) and all-cause mortality risks (RR 1.14, 95%CI [1.05-1.23]) compared to not using P-gp/CYP3A4 inhibitors, while the risks of stroke/systemic embolism (RR 0.88, 95%CI [0.77-1.01]), intracranial bleeding (RR 0.89, 95%CI [0.68-1.15]) and gastrointestinal bleeding (RR 1.09, 95%CI [0.91-1.30]) were not significantly different. Concomitant use of amiodarone with NOACs was associated with lower thromboembolic (RR 0.75, 95%CI [0.61-0.92]), similar major bleeding (RR 0.92, 95%CI [0.80-1.07]) but higher mortality risks (RR 1.21, 95%CI [1.05-1.39]). Coadministration of verapamil or diltiazem was associated with higher major bleeding risks (RR 1.64, 95%CI [1.31-2.06]), but comparable thromboembolic (RR 1.10, 95%CI [0.75-1.61]) and mortality risks (RR 1.01, 95%CI [0.77-1.33]). CONCLUSION: Given the higher bleeding and mortality risks in NOAC-treated AF patients concomitantly using P-gp/CYP3A4 inhibitors, close monitoring is warranted.

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.

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis.

PURPOSE: Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed. METHODS AND RESULTS: After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m2, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients. CONCLUSION: The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m2) and on differences between NOACs in these patients.

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.