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

The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug–drug interaction (DDI):Co-medication of metoprolol and paroxetine or fluoxetine in the elderly

Purpose: Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. Method: Dispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (60years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005. Results: A total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences=3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences=1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences=2320) than paroxetine/fluoxetine users (incidences=1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD=0.47) regardless whether they were prescribed paroxetine/fluoxetine. Conclusion: Despite the signalling software, metoprolol-paroxetine/fluoxetine combinations are still observed in the elderly population. The clinical impact of these interactions needs further investigation

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

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

Contains fulltext : 218240.pdf (Publisher’s version ) (Open Access)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

The impact of CYP2D6 mediated drug-drug interaction:A systematic review on a combination of metoprolol and paroxetine/fluoxetine

AIM: Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI. METHOD: Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087). RESULTS: We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol-related side effects. In a case-control study, the DDI was not significantly associated with bradycardia. CONCLUSION: Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta-blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol-related side effects is necessary

Improving antibacterial prescribing safety in the management of COPD exacerbations:systematic review of observational and clinical studies on potential drug interactions associated with frequently prescribed antibacterials among COPD patients

BACKGROUND: Guidelines advise the use of antibacterials (ABs) in the management of COPD exacerbations. COPD patients often have multiple comorbidities, such as diabetes mellitus and cardiac diseases, leading to polypharmacy. Consequently, drug-drug interactions (DDIs) may frequently occur, and may cause serious adverse events and treatment failure. OBJECTIVES: (i) To review DDIs related to frequently prescribed ABs among COPD patients from observational and clinical studies. (ii) To improve AB prescribing safety in clinical practice by structuring DDIs according to comorbidities of COPD. METHODS: We conducted a systematic review by searching PubMed and Embase up to 8 February 2018 for clinical trials, cohort and case-control studies reporting DDIs of ABs used for COPD. Study design, subjects, sample size, pharmacological mechanism of DDI and effect of interaction were extracted. We evaluated levels of DDIs and quality of evidence according to established criteria and structured the data by possible comorbidities. RESULTS: In all, 318 articles were eligible for review, describing a wide range of drugs used for comorbidities and their potential DDIs with ABs. DDIs between ABs and co-administered drugs could be subdivided into: (i) co-administered drugs altering the pharmacokinetics of ABs; and (ii) ABs interfering with the pharmacokinetics of co-administered drugs. The DDIs could lead to therapeutic failures or toxicities. CONCLUSIONS: DDIs related to ABs with clinical significance may involve a wide range of indicated drugs to treat comorbidities in COPD. The evidence presented can support (computer-supported) decision-making by health practitioners when prescribing ABs during COPD exacerbations in the case of co-medication

Informational needs of general practitioners regarding discharge medication: content, timing and pharmacotherapeutic advice

textabstractObjective: To investigate the needs of Dutch general practitioners on discharge medication, both regarding content, timing and the appreciation of pharma-cotherapeutic advices from clinical pharmacists. Setting: A general teaching hospital in Amsterdam, the Netherlands. Method: A prospective observational study was performed. A questionnaire with regard to the content, optimal timing (including way of information transfer) and appreciation of pharmacotherapeutic advices was posted to 464 general practitioners. One reminder was sent. Main outcome measure: Description of the needs of general practitioners was assessed. For each question and categories of comments frequency tables were made. The Fisher-exact test was used to study associations between the answers to the questions. Results: In total, 149 general practitioners (32%) responded. Most general practitioners (75%) experienced a delay in receiving discharge medication information and preferred to receive this on the day of discharge. GPs wished to receive this information mainly through e-mail (44%). There was a significant correlation (P = 0.002) between general practitioners who wanted to know whether and why medication had been stopped (87%) and changed (88%) during hospital admission. The general practitioners (88%) appreciated pharmacotherapeutic advices from clinical pharmacists. Conclusion: This study indicates how information transfer on discharge medication to GPs can be optimised in the Netherlands. The information arrives late and GPs want to be informed on the day of discharge mainly by e-mail. GPs wish to know why medication is changed or discontinued and appreciate pharmacotherapeutic advices from clinical pharmacists

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

The use of opioids at the end of life: the knowledge level of Dutch physicians as a potential barrier to effective pain management

<p>Abstract</p> <p>Background</p> <p>Pain is still one of the most frequently occurring symptoms at the end of life, although it can be treated satisfactorily in most cases if the physician has adequate knowledge. In the Netherlands, almost 60% of the patients with non-acute illnesses die at home where end of life care is coordinated by the general practitioner (GP); about 30% die in hospitals (cared for by clinical specialists), and about 10% in nursing homes (cared for by elderly care physicians).</p> <p>The research question of this study is: what is the level of knowledge of Dutch physicians concerning pain management and the use of opioids at the end of life?</p> <p>Methods</p> <p>A written questionnaire was sent to a random sample of physicians of specialties most often involved in end of life care in the Netherlands. The questionnaire was completed by 406 physicians, response rate 41%.</p> <p>Results</p> <p>Almost all physicians were aware of the most basal knowledge about opioids, e.g. that it is important for treatment purposes to distinguish nociceptive from neuropathic pain (97%). Approximately half of the physicians (46%) did not know that decreased renal function raises plasma concentration of morphine(-metabolites) and 34% of the clinical specialists erroneously thought opioids are the favoured drug for palliative sedation.</p> <p>Although 91% knew that opioids titrated against pain do not shorten life, 10% sometimes or often gave higher dosages than needed with the explicit aim to hasten death. About half felt sometimes or often pressured by relatives to hasten death by increasing opioiddosage.</p> <p>The large majority (83%) of physicians was interested in additional education about subjects related to the end of life, the most popular subject was opioid rotation (46%).</p> <p>Conclusions</p> <p>Although the basic knowledge of physicians was adequate, there seemed to be a lack of knowledge in several areas, which can be a barrier for good pain management at the end of life. From this study four areas emerge, in which it seems likely that an improvement can improve the quality of pain management at the end of life for many patients in the Netherlands: 1)palliative sedation; 2)expected effect of opioids on survival; and 3) opioid rotation.</p

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

INTRODUCTION: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. METHODS AND ANALYSIS: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. ETHICS AND DISSEMINATION: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings