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.

The Development and Proof of Principle Test of TRIAGE: A Practical Question Set to Identify and Discuss Medication-Related Problems in Community Pharmacy.

The pharmacy counter is a good place to identify and discuss medication-related problems. However, there is a lack of practical communication tools to support pharmacy technicians (PTs) in initiating a conversation with patients. This study aimed to develop and test a practical set of questions for PTs, called TRIAGE, to identify problems during encounters. TRIAGE was developed based on insight from the literature, focus groups with PTs and pharmacists, and input from patients and experts. In 10 community pharmacies, 17 PTs used TRIAGE during encounters with patients who collected their cardiovascular medication. For each encounter, PTs registered the identified problems and suggested solutions. A total of 105 TRIAGE conversations were held, 66 for first refill and 39 for follow-up refill prescriptions. In 15 (23%) first refill prescription encounters, a problem was identified. These problems concerned forgetting to take the medication, a complex medication regime or (fear of) side effects. In three (8%) follow-up refill prescription encounters, a problem was identified. Most of the problems were solved on the spot. Pharmacy technicians indicated that they identified medication-related problems with TRIAGE that otherwise would be left unnoticed. They appreciated TRIAGE as a useful instrument for starting the conversation with patients about medication use.

Exposure Variability and Target Attainment of Vancomycin: A Systematic Review Comparing Intermittent and Continuous Infusion.

BACKGROUND: Studies comparing the clinical outcomes between vancomycin intermittent infusion (InI) and continuous infusion (CoI) treated patients are generally underpowered. Moreover, due to large differences in the design and efficacy end points in these studies, a meta-analysis of the currently available data is not feasible. Therefore, this systematic review aimed to compare the exposure variability and target attainment with vancomycin during InI and CoI. PATIENTS AND METHODS: A literature search was performed, and clinical studies reporting on vancomycin-treated populations were selected. After exclusion of reviews, case reports, and articles not published in the English language, 505 articles were screened for reported data on vancomycin serum concentrations. A total of 34 studies were included in the review. Relative standard deviations reported in the included studies were assessed, and vancomycin serum concentration variability and target attainment were compared between vancomycin InI and CoI. RESULTS: The variability in serum concentrations was significantly larger for InI than for CoI (relative standard deviations 46.5% and 32.1%, respectively; P = 0.001). Notably, variability appeared to be independent of the study population or design. Studies directly comparing target attainment between both modes of administration denoted higher and faster target attainment with CoI in all instances. CONCLUSIONS: In conclusion, CoI was associated with lower variabilities in the serum concentration and favorable target attainment rates compared with InI. These findings are important because vancomycin exposure is considered a major predictor of the patients' clinical outcomes. However, the role of lower serum concentration variability and higher target attainment rates in achieving better clinical outcomes needs to be evaluated in patients treated with vancomycin CoI compared with InI.

Switching From Intermittent to Continuous Infusion of Vancomycin in Critically Ill Patients: Toward a More Robust Exposure.

BACKGROUND: To increase target attainment rates, switching the mode of administration from intermittent (InI) to continuous infusion (CoI) has been proposed. In this study, target attainment rates and interpatient variation in exposure were compared between vancomycin InI- and CoI-treated critically ill patients. METHODS: An observational cohort study was conducted among critically ill patients admitted to a level-2 intensive care unit. Adult patients (18 years or older) treated with intravenous vancomycin for various indications, including sepsis, pneumonia, and endocarditis between 2007 and 2013 were eligible for inclusion. In 2010, vancomycin mode of administration switched from intermittent to continuous. Vancomycin was administered through intravenous infusion, and dosing was guided by therapeutic drug monitoring. Target attainment rates and variations in serum concentration and estimated area under the curve (AUC) were compared between groups. RESULTS: The target attainment rate for therapeutic vancomycin exposure was higher in the group treated with CoI than in patients treated with InI (48% versus 19%, P < 0.001). Furthermore, between-patient variation in vancomycin serum concentration was nearly twice as high in intermittently infused patients compared with continuously infused patients. Finally, the correlation between serum concentration and AUC was stronger among patients on vancomycin continuous infusion than that of the intermittently dosed group (r 0.93 versus 0.72). CONCLUSIONS: Switching from intermittent to continuous infusion of vancomycin in a critically ill population provided higher target attainment rates and a more robust drug exposure. Furthermore, continuous infusion yielded stronger concentration-AUC correlations facilitating a single sample therapeutic drug monitoring strategy with AUC targets. A switch to continuous infusion may therefore improve clinical outcomes in vancomycin-treated critically ill patients.