Tacrolimus (TAC) is a narrow-therapeutic-range immunosuppressant drug used after organ transplantation. A therapeutic failure is possible if drug levels are not within the therapeutic range after the first year of treatment. Pharmacogenetic variants and drug–drug interactions (DDIs) are involved. We describe a patient case of a young man (16 years old) with a renal transplant receiving therapy including TAC, mycophenolic acid (MFA), prednisone and omeprazole for prophylaxis of gastric and duodenal ulceration. The patient showed great fluctuation in TAC blood concentration/oral dose ratio, as well as pharmacotherapy adverse effects (AEs) and frequent diarrhea episodes. Additionally, decreased kidney function was found. A pharmacotherapeutic follow-up, including pharmacogenetic analysis, was carried out. The selection of the genes studied was based on the previous literature (CYP3A5, CYP3A4, POR, ABCB1, PXR and CYP2C19). A drug interaction with omeprazole was reported and the nephrologist switched to rabeprazole. A lower TAC concentration/dose ratio was achieved, and the patient’s condition improved. In addition, the TTT haplotype of ATP Binding Cassette Subfamily B member 1 (ABCB1) and Pregnane X Receptor (PXR) gene variants seemed to affect TAC pharmacotherapy in the studied patient and could explain the occurrence of long-term adverse effects post-transplantation. These findings suggest that polymorphic variants and co-treatments must be considered in order to achieve the effectiveness of the immunosuppressive therapy with TAC, especially when polymedicated patients are involved. Moreover, pharmacogenetics could influence the drug concentration at the cellular level, both in lymphocyte and in renal tissue, and should be explored in future studies.

Achieving clinical effectiveness with vitamin K antagonists (VKAs) requires a Time in Therapeutic Range (TTR) above 65%. TTR is influenced by genetics (CYP2C9, VKORC1, CYP4F2), treatment adherence, and knowledge. The SAMe-TT2R2 algorithm is used to assess VKA treatment suitability. In this case report, SAMe-TT2R2 and pharmacogenetic analysis were used to improve oral anticoagulant management in a patient with poor control of INR. An 84-year-old, obese male with atrial fibrillation, undergoing acenocoumarol therapy, had a suboptimal TTR. An assessment with the SAMe-TT2R2 algorithm indicated a favorable profile for VKA use. An educational intervention on vitamin K-rich foods was conducted, and his physician was informed about the interaction between omeprazole and acenocoumarol, recommending its replacement with pantoprazole. This intervention was accepted by the physician and, three months post-intervention, the patient’s TTR improved to 100%. Poor adherence and limited knowledge contributed to treatment failures in patients with a good VKA profile. Pharmaceutical interventions significantly improved TTR management. Patients with favorable genetic and clinical profiles could achieve adequate control of their anticoagulant medication through these interventions. Predictive tools may help select patients who can effectively and safely use VKAs through pharmaceutical interventions.

“Protégete del sol, protégete del Lupus”. Integración curricular en el grado de Farmacia a través de la Metodología aprendizaje Servicio

Introduction Poor long-term adherence to antihypertensive medication remains a major challenge in hypertension management, particularly among older adults, contributing to suboptimal blood pressure control, cardiovascular morbidity and reduced quality of life. Nurse-led educational and behavioural interventions delivered in primary care may improve medication adherence; however, evidence from pragmatic cluster randomised trials integrated into routine clinical practice remains limited. This study aims to evaluate whether a nurse-led multidimensional educational and behavioural intervention improves adherence to antihypertensive treatment among older adults with hypertension in primary care. Methods and analysis NURSE-ADHERE-HTN is an ongoing pragmatic, open-label, cluster randomised controlled trial being conducted in 14 primary care centres of the Navarra Health Service–Osasunbidea, Spain. The trial was prospectively registered in the ISRCTN registry (ISRCTN35559821). Primary care centres were centrally allocated in a 1:1 ratio to the intervention or usual-care group, with seven centres per group and two participating nurses per centre. The target sample size is 280 participants aged 60 years or older with hypertension, prescribed at least one antihypertensive medication and identified as non-adherent using the 4-item Morisky Medication Adherence Scale (MMAS-4). The intervention consists of a nurse-led multidimensional educational and behavioural programme integrated into routine primary care, comprising individualised education, motivational interviewing, review of antihypertensive treatment and medication-taking routines, Mediterranean diet counselling, physical activity support and telephone reinforcement. The primary outcome will be adherence to antihypertensive treatment at 6 months, assessed using the MMAS-4 in accordance with the licensed wording, structure and standardised scoring method. Adherence will also be assessed at baseline and 12 months, with the 12-month assessment used to evaluate whether any intervention effect observed at 6 months is maintained over time. Electronic prescription dispensing records will provide a complementary measure of adherence. Secondary outcomes will include blood pressure assessed using 24-hour ambulatory monitoring, health-related quality of life, cardiovascular-related emergency department visits and hospital admissions, symptoms of anxiety and depression, Mediterranean diet adherence, physical activity, reasons for non-adherence, anthropometric and selected laboratory variables, medication burden and concordance between adherence measures. Outcomes will be assessed at baseline, 6 months and 12 months. Prespecified exploratory analyses will assess effect modification by sex. Statistical analyses will account for clustering at the primary care centre level. Ethics and dissemination The study was approved by the Navarra Clinical Research Ethics Committee (reference PI_2023/92). Written informed consent is obtained from all participants before enrolment. Findings will be disseminated through peer-reviewed publications, conference presentations and reports to healthcare stakeholders. Trial registration number ISRCTN35559821.

Introduction: Anticoagulation treatment with VKA presents an optimal risk-benefit balance in patients with a Time in Therapeutic Range (TTR) >70%. Pharmacist integration in the primary health care team, using innovative tools such as the SAME-TT2R2 and pharmacogenetics information, could enhance the management of anticoagulated patients. This study aims to assess the effectiveness of a medication review with follow up service by community pharmacists, in collaboration with Primary Care for patients treated with VKA. Methods and analysis: A randomized controlled study with blinded outcome assessment will be conducted. Patients treated with VKA with TTR<70% from 2 health care centres will be included. Primary outcome is TTR during last 6 months. Secondary outcomes will be: adherence, vitamin K intake, patient’s knowledge, pharmacogenetics and SAME-TT2R2’s clinical utility, costs, quality of life and satisfaction. Potential clinical, economic, and humanistic impact of the interventions will be retrospectively analysed using CLEO tool. Intervention group will receive a medication review with follow up, physicians will receive an evidence-based report patient´s medicine-related problems, genetic and clinical limitations for the use of VKA. Patients will be followed for 6 months. Sample size: 130 patients will be recruited for 90% power based on the most conservative scenarios. Multivariate, cost-effectiveness analyses will be used. Ethics and dissemination: The study design was approved by the ethical committee of Aragon. The trial is registered at Clinical Trials.gov dated 25/05/2017: NCT03154489. Trial results will be published in peer-reviewed journals and at conferences.