Developing practical recommendations for drug-disease interactions in patients with hypertension.

Background: Hypertension, a significant risk factor for cardiovascular diseases, demands proactive management as cardiovascular diseases remain the leading cause of death worldwide. Reducing systolic and diastolic blood pressure levels below recommended reference values of <140/90 mmHg can lead to a significant reduction of the risk of CVD and all-cause mortality. However, treatment of hypertension can be difficult and the presence of comorbidities could further complicate this treatment. Drugs used to manage these comorbidities may inadvertently have an impact on blood pressure, resulting in a phenomenon known as drug-disease interaction. This study aims to assess the safety of medication that can affect blood pressure in patients with hypertension and provide practical recommendations for healthcare professionals. Methods: For the development of recommendations for the drug-disease interaction (DDSI) hypertension, a six-step plan that combined literature selection and multidisciplinary expert opinion was used. The process involved (1) defining the scope of the DDSI and selecting relevant drugs, (2) collecting evidence, (3) data-extraction, (4) reaching of expert consensus, (5) publication and implementation of the recommendations in healthcare systems and (6) updating the information. Results: An increase of 10 mmHg in systolic blood pressure and 5 mmHg in diastolic blood pressure was defined as clinically relevant. Corticosteroids, danazol, and yohimbine caused a clinically relevant DDSI with hypertension. Several other drugs with warnings for hypertension in the official product information were assessed to have no clinically relevant DDSI due to minor influence or lack of data on blood pressure. Drugs with evidence for a relevant change in blood pressure which are prescribed under close monitoring of blood pressure according to clinical guidelines, were deemed to be not clinically relevant for signalling. Conclusion: This study provides specific recommendations that can be implemented directly in clinical practice, for example, in clinical decision support systems, potentially resulting in safer drug use in patients with hypertension and better healthcare by reducing alert fatigue. Future research should focus on evaluating the effectiveness of implementation strategies and their impact on reducing unsafe use of medication in patients with hypertension.

Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.

PURPOSE: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. METHODS: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. RESULTS: Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C. CONCLUSION: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.

High-throughput Analysis of Capillary Density in Skeletal Muscle Cross Sections.

Capillary density in skeletal muscles is key to estimate exercise capacity in healthy individuals, athletes, and those with muscle-related pathologies. Here, we present a step-by-step, high-throughput semi-automated method for quantifying capillary density from whole human skeletal muscle cross-sections, in areas of the muscle occupied by myofibers. We provide a detailed protocol for immunofluorescence staining, image acquisition, processing, and quantification. Image processing is performed in ImageJ, and data analysis is conducted in R. The provided protocol allows high-throughput quantification of capillary density. Key features • This protocol builds upon the method and results described in Abbassi-Daloii et al. (2023b). • It includes step-by-step details on image acquisition and image processing of the entire muscle section. • It enables high-throughput and semi-automated image quantification of capillary density. • It provides a robust analysis for determining capillary density over the entire muscle cross section.

Facile electrochemical affinity measurements of small and large molecules.

A novel miniaturized sensor for electrochemical detection that contains graphene- and gold nanoparticles was functionalized with proteins. Using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) it was possible to observe and quantify interactions of molecules with these proteins. The protein binders included carbohydrate ligands as small as carbohydrates up to COVID-19 spike protein variants engaged in protein-protein interactions. The system uses off-the-shelf sensors combined with an affordable potentiostat and yet is sensitive enough for small ligand binding.

Hydrogen Evolution Electrocatalysis with a Molecular Cobalt Bis(alkylimidazole)methane Complex in DMF: a Critical Activity Analysis.

[Co(HBMIMPh2 )2 ](BF4 )2 (1) [HBMIMPh2 =bis(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)methane] was investigated for its electrocatalytic hydrogen evolution performance in DMF using voltammetry and during controlled potential/current electrolysis (CPE/CCE) in a novel in-line product detection setup. Performances were benchmarked against three reported molecular cobalt hydrogen evolution reaction (HER) electrocatalysts, [Co(dmgBF2 )2 (solv)2 ] (2) (dmgBF2 =difluoroboryldimethylglyoximato), [Co(TPP)] (3) (TPP=5,10,15,20-tetraphenylporphyrinato), and [Co(bapbpy)Cl](Cl) (4) [bapbpy=6,6'-bis-(2-aminopyridyl)-2,2'-bipyridine], showing distinct performances differences with 1 being the runner up in H2 evolution during CPE and the best catalyst in terms of overpotential and Faradaic efficiency during CCE. After bulk electrolysis, for all of the complexes, a deposit on the glassy carbon electrode was observed, and post-electrolysis X-ray photoelectron spectroscopy (XPS) analysis of the deposit formed from 1 demonstrated only a minor cobalt contribution (0.23 %), mainly consisting of Co2+ . Rinse tests on the deposits derived from 1 and 2 showed that the initially observed distinct activity was (partly) preserved for the deposits. These observations indicate that the molecular design of the complexes dictates the features of the formed deposit and therewith the observed activity.

Combining metal-metal cooperativity, metal-ligand cooperativity and chemical non-innocence in diiron carbonyl complexes.

Several metalloenzymes, including [FeFe]-hydrogenase, employ cofactors wherein multiple metal atoms work together with surrounding ligands that mediate heterolytic and concerted proton-electron transfer (CPET) bond activation steps. Herein, we report a new dinucleating PNNP expanded pincer ligand, which can bind two low-valent iron atoms in close proximity to enable metal-metal cooperativity (MMC). In addition, reversible partial dearomatization of the ligand's naphthyridine core enables both heterolytic metal-ligand cooperativity (MLC) and chemical non-innocence through CPET steps. Thermochemical and computational studies show how a change in ligand binding mode can lower the bond dissociation free energy of ligand C(sp3)-H bonds by ∼25 kcal mol-1. H-atom abstraction enabled trapping of an unstable intermediate, which undergoes facile loss of two carbonyl ligands to form an unusual paramagnetic (S = ) complex containing a mixed-valent iron(0)-iron(i) core bound within a partially dearomatized PNNP ligand. Finally, cyclic voltammetry experiments showed that these diiron complexes show catalytic activity for the electrochemical hydrogen evolution reaction. This work presents the first example of a ligand system that enables MMC, heterolytic MLC and chemical non-innocence, thereby providing important insights and opportunities for the development of bimetallic systems that exploit these features to enable new (catalytic) reactivity.

Efficiency of different flows for apneic oxygenation when using high flow nasal oxygen application - a technical simulation.

BACKGROUND: Preoxygenation and application of apneic oxygenation are standard to prevent patients from desaturation e.g. during emergency intubation. The time before desaturation occurs can be prolonged by applying high flow oxygen into the airway. Aim of this study was to scientifically assess the flow that is necessary to avoid nitrogen entering the airway of a manikin model during application of pure oxygen via high flow nasal oxygen. METHODS: We measured oxygen content over a 20-min observation period for each method in a preoxygenated test lung applied to a human manikin, allowing either room air entering the airway in control group, or applying pure oxygen via high flow nasal oxygen at flows of 10, 20, 40, 60 and 80 L/min via nasal cannula in the other groups. Our formal hypothesis was that there would be no difference in oxygen fraction decrease between the groups. RESULTS: Oxygen content in the test lung dropped from 97 ± 1% at baseline in all groups to 43 ± 1% in the control group (p < 0.001 compared to all other groups), to 92 ± 1% in the 10 L/min group, 92 ± 1% in the 20 L/min group, 90 ± 1% in the 40 L/min group, 89 ± 0% in the 60 L/min group and 87 ± 0% in the 80 L/min group. Apart from comparisons 10 l/ min vs. 20 L/min group (p = .715) and 10/L/min vs. 40 L/min group (p = .018), p was < 0.009 for all other comparisons. CONCLUSIONS: Simulating apneic oxygenation in a preoxygenated manikin connected to a test lung over 20 min by applying high flow nasal oxygen resulted in the highest oxygen content at a flow of 10 L/min; higher flows resulted in slightly decreased oxygen percentages in the test lung.

Management of drug-disease interactions: a best practice from the Netherlands.

Background Drug-disease interactions are situations where pharmacotherapy may have a negative effect on patients' comorbidities. In these cases, it can be necessary to avoid that drug, adjust its dose or monitor therapy. In the Netherlands, pharmacists have developed a best practice how to systematically evaluate drug-disease interactions based on pharmacological considerations and implement recommendations for specific drug-disease interactions. Aim To describe the development of recommendations for drug-disease interactions and the implementation in prescribing and dispensing practice in the Netherlands. Setting Pharmacies and physicians' practices in primary care and hospitals in the Netherlands. Development A multi-disciplinary expert panel assessed if diseases had clinically relevant drug-disease interactions and evaluated drug-disease interactions by literature review and expert opinion, and subsequently developed practice recommendations. Implementation The recommendations were implemented in all clinical decision support systems in primary care and hospitals throughout the Netherlands. Evaluation Recommendations were developed for 57 diseases and conditions. Cardiovascular diseases have the most drug-disease interactions (n = 12, e.g. long QT-syndrome, heart failure), followed by conditions related to the reproductive system (n = 7, e.g. pregnancy). The number of drugs with recommendations differed between 6 for endometriosis and tympanostomy tubes, and up to 1171 in the case of porphyria or even all drugs for pregnancy. Conclusion Practice recommendations for drug-disease interactions were developed, and implemented in prescribing and dispensing practice. These recommendations support both pharmacists and physicians by signalling clinically relevant drug-disease interactions at point of care, thereby improving medication safety. This practice may be adopted and contribute to safer medication use in other countries as well.

Medication-Related Problems in Liver Transplant Recipients in the Outpatient Setting: A Dutch Cohort Study.

Background: After liver transplantation (LTx), adherence to immunosuppressive medication and avoidance of contra-indicated drugs is essential for long-term survival. This study aimed to investigate the prevalence, types and severity of medication-related problems (MRPs) and interventions initiated by a clinical pharmacist (CP) in a cohort of LTx recipients in the outpatient setting. Method: This study was a retrospective, observational study in LTx recipients that visited the outpatient clinic for an annual check-up. A 20-minutes consultation with a CP consisted of medication reconciliation and consultation about medication, adherence, and adverse drug reactions (ADRs). Discrepancies between actual and intended drug use, and MRPs were identified and the severity of MRPs was assessed. Potential interventions were discussed with the patient and the treating physician and evaluated after one year. Results: The CP counseled 64 LTx recipients and found 96 discrepancies in 37 patients. Most discrepancies (60.4%, n = 58) concerned missing medications. In total, 98 MRPs were identified in 53 patients (median 2; range 1-5 per patient), with a total of 113 interventions. Most frequent MRPs were: ADRs (22.4%, n = 22), nonadherence (19.3%, n = 19), unnecessary drugs (16.3%, n = 16) and undertreatment (12.2%, n = 12). Interventions most frequently proposed included optimization of dosage regimen (21.2%, n = 24), individualized recommendation regarding compliance (16.8%, n = 19) and drug discontinuation (12.4%, n = 14). After one year, 15 of the 19 patients (79%) experienced no longer compliance issues and 27 of the 29 patients (93%) used no drugs with indication issues anymore. Conclusion: The CP in an outpatient monitoring program for LTx recipients can signal relevant discrepancies and MRPs. This leads to interventions that are accepted by both the patients and the physicians, with a positive effect after one year.

[Allergic reactions to COVID-19 vaccines]. / Overgevoeligheidsreacties op covid-19-vaccins.

In 2021 many people in the Netherlands will be vaccinated against COVID-19. The mass vaccination and the new types of vaccines trigger questions about the safety of these vaccines. In this paper we discuss: (1) what reactions are expected from COVID-19 vaccines, (2) what precautions are needed when vaccinating people, and (3) how to act when allergic reactions occur. The COVID-19 vaccines include the first vaccines produced with the mRNA platform. The most frequent adverse reactions are comparable with other vaccines. Allergic reactions to COVID-19 vaccines are rare but can occur. These reactions may be related to excipients in the vaccines, like polyethylene glycol. In case of a possible allergic reaction, a doctor, in consultation with an allergist, can investigate whether vaccination is safe in the future and whether precautions are necessary. Allergic reactions to vaccine components must be recorded completely and unambiguously in the patient file.

No association between use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID-19 in the COvid MEdicaTion (COMET) study.

Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.

Development of Comprehensible Prescription Label Instructions: A Study Protocol for a Mixed-Methods Approach.

INTRODUCTION: Patients receive information about their medication from different sources, including prescription labels. These labels are physically attached to each package dispensed to patients and contain the most important instructions on how to use the medication correctly. However, many patients experience difficulties in understanding and applying the instructions on these labels correctly, especially patients with limited health literacy. The aim of this study is to investigate the comprehensibility of prescription label instructions among patients with adequate and limited health literacy skills, and to implement improvements in primary health care. METHODS: We used a mixed-methods approach, which consisted of four phases. Phase 1 (desk research) was divided into a systematic literature review on the comprehensibility of prescription label instructions (1a) and a content analysis of the textual elements in Dutch prescription label instructions (1b). In phase 2 (patient studies), semi-structured interviews were conducted to investigate the comprehensibility of seven prescription labels among patients with different health literacy skills (2a), and a quantitative study in which the comprehensibility of six optimized prescription labels was compared among patients with different health literacy skills (2b). Patient studies were conducted in eight Dutch pharmacies. In phase 3 optimized prescription label instructions were implemented in national medication databases which has been supported by a guideline (3a), and education of pharmacy workers (3b). Phase 4 consists of evaluating the optimized prescription label instructions by experiences from patients and pharmacists. ANTICIPATED RESULTS: This mixed-methods approach will result in scientific publications of the individual studies, and a guideline on how to compose comprehensible prescription label instructions to be put on medication packages. Optimized prescription label instructions will be implemented in national medication databases. DISCUSSION: This protocol describes a mixed-method research to compose and implement comprehensible prescription label instructions and will lead to knowledge about the comprehensibility of textual elements in these labels, with specific attention for patients with limited health literacy. Implementation of optimized prescription label instructions will lead to a better understanding of them, which may contribute to improved medication adherence. A limitation is that non-textual aspects of prescription labels are not investigated.

The Development of Practice Recommendations for Drug-Disease Interactions by Literature Review and Expert Opinion.

BACKGROUND: Drug-disease interactions negatively affect the benefit/risk ratio of drugs for specific populations. In these conditions drugs should be avoided, adjusted, or accompanied by extra monitoring. The motivation for many drug-disease interactions in the Summary of Product Characteristics (SmPC) is sometimes insufficiently supported by (accessible) evidence. As a consequence the translation of SmPC to clinical practice may lead to non-specific recommendations. For the translation of this information to the real world, it is necessary to evaluate the available knowledge about drug-disease interactions, and to formulate specific recommendations for prescribers and pharmacists. The aim of this paper is to describe a standardized method how to develop practice recommendations for drug-disease interactions by literature review and expert opinion. METHODS: The development of recommendations for drug-disease interactions will follow a six-step plan involving a multidisciplinary expert panel (1). The scope of the drug-disease interaction will be specified by defining the disease and by describing relevant effects of this drug-disease interaction. Drugs possibly involved in this drug-disease interaction are selected by checking the official product information, literature, and expert opinion (2). Evidence will be collected from the official product information, guidelines, handbooks, and primary literature (3). Study characteristics and outcomes will be evaluated and presented in standardized reports, including preliminary conclusions on the clinical relevance and practice recommendations (4). The multidisciplinary expert panel will discuss the reports and will either adopt or adjust the conclusions (5). Practice recommendations will be integrated in clinical decision support systems and published (6). The results of the evaluated drug-disease interactions will remain up-to-date by screening new risk information, periodic literature review, and (re)assessments initiated by health care providers. ACTIONABLE RECOMMENDATIONS: The practice recommendations will result in advices for specific DDSI. The content and considerations of these DDSIs will be published and implemented in all Clinical Decision Support Systems in the Netherlands. DISCUSSION: The recommendations result in professional guidance in the context of individual patient care. The professional will be supported in the decision making in concerning pharmacotherapy for the treatment of a medical problem, and the clinical risks of the proposed medication in combination with specific diseases.

COvid MEdicaTion (COMET) study: protocol for a cohort study.

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19.

Prevalence and Accuracy of Information on CYP2D6, CYP2C19, and CYP2C9 Related Substrate and Inhibitor Co-Prescriptions in the General Population: A Cross-Sectional Descriptive Study as Part of the PharmLines Initiative.

BACKGROUND: Drug-drug interaction (DDI) is one of the main contributors to adverse drug reactions and therefore, it is important to study its frequency in the population. We aimed to investigate frequency and concordance on CYP2D6, CYP2C19, and CYP2C9 (CYP2D6/2C19/2C9)-mediated potential DDIs at the Lifelines cohort and linked data from the pharmacy database IADB.nl. METHODS: As part of the University of Groningen PharmLines Initiative, data were collected on CYP2D6/2C19/2C9-related substrate/inhibitors from entry questionnaires of Lifelines participants and linked information from the pharmacy database IADB.nl. CYP2D6/2C19/2C9 related co-prescriptions were divided based on the type of drugs i.e. chronically used medication (CM) or occasionally used medication (OM). This resulted in the combination of two chronically used drugs (CM-CM), chronically and occasionally used medication (CM-OM), and two occasionally used drugs (OM-OM). To measure the agreement level, cohen's kappa statistics and test characteristics were used. Results were stratified by time window, gender, and age. RESULTS: Among 80,837 medicine users in the Lifelines, about 1-2 per hundred participants were exposed to a CYP2D6/2C19/2C9-mediated potential DDI. Overall, the overlapping time window of three months produced the highest mean kappa values between the databases i.e. 0.545 (95% CI:0.544-0.545), 0.512 (95% CI:0.511-0.512), and 0.374 (95% CI:0.373-0.375), respectively. CM-CM had a better level of agreement (good) than CM-OM (fair to moderate) and OM-OM combination (poor to moderate). The influence of gender on concordance values was different for different CYPs. Among older persons, agreement levels were higher than for the younger population. CONCLUSIONS: CYP2D6/2C19/2C9-mediated potential DDIs were frequent and concordance of data varied by time window, type of combination, sex and age. Subsequent studies should rather use a combination of self-reported and pharmacy database information.

Medication safety in patients with hepatic impairment: A survey of community pharmacists' knowledge level and their practice in caring for these patients.

AIMS: To study community pharmacists' level of knowledge on medication safety in patients with hepatic impairment and their practice in caring for these patients. METHODS: Pharmacists from Dutch community pharmacies (n = 1545) were invited to participate in an online survey. The survey consisted of 27 questions covering 2 main topics: knowledge and current practice. The level of knowledge was measured by a 6-item knowledge test. Multiple linear regression was used to identify predictors of correctly answered responses. RESULTS: In total, 338 pharmacists (22%) completed the questionnaire. The mean knowledge score was 2.8 (standard deviation 1.6). Only 30.3% of respondents were able to appropriately advise on use of analgesics in severe cirrhosis. Postgraduate education on hepatic impairment, knowledge of recently developed practical guidance, and fewer years of practice were associated with a higher level of knowledge. In total, 70.4% indicated to evaluate medication safety in a patient with hepatic impairment at least once weekly. In the past 6 months, 83.3% of respondents consulted a prescriber about a patient with hepatic impairment. Frequently encountered barriers in practice were insufficient knowledge on the topic and a lack of essential patient information (i.e. diagnosis and severity of the impairment). CONCLUSION: Community pharmacists regularly evaluate the safety of medication in patients with hepatic impairment, yet their level of knowledge was insufficient and additional education is needed. Pharmacists experienced several difficulties in providing pharmaceutical care. If these issues are resolved, pharmacists can play a more active role in ensuring medication safety in their patients with hepatic impairment.

Safe use of medication in patients with cirrhosis: pharmacokinetic and pharmacodynamic considerations.

Introduction: The global burden of cirrhosis is rising, and clinicians increasingly face the challenge of safely prescribing medicines for complications of hepatic disease and comorbidities. Prescribing in patients with cirrhosis is complicated by alterations that can occur in the pharmacology of medicines.Areas covered: This paper provides an overview of current knowledge on the pharmacokinetics and pharmacodynamics of medicines in patients with cirrhosis. We describe the pathophysiological changes that occur and their consequences on pharmacokinetic parameters. We explain that the influence of cirrhosis on the pharmacokinetics depends on several drug and patient characteristics. Patients with cirrhosis also have an increased susceptibility to some toxicological effects of medicines, such as renal impairment and hematological toxicity, which we describe in detail. In addition, we discuss approaches to apply this knowledge in practice and improve safe medication use in patients with cirrhosis.Expert opinion: Tailored pharmacotherapy is needed to ensure safe and appropriate use of medicines in patients with cirrhosis. Clinicians are supported by freely available recommendations on safe drug use in cirrhosis published on a website. In addition, a regular evaluation of medication use in patients with cirrhosis could resolve and prevent medication-related problems.