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Polypharmacy in older adults represents a global challenge in public health, especially in the use of psychotropic drugs, requiring more effective management to ensure optimal treatments and minimize associated risks. Methods: This descriptive study was based on the documentary analysis of bibliographic sources from Scielo, Medigraphic, Scopus, Science Direct, PubMed and Elsevier, with emphasis on polyneuropsychopharmacy in the geriatric population. In addition, the bibliographic organization was carried out through the Mendeley manager and the descriptors “polypharmacy” and “older person” were used, obtained from the Health Sciences category, selecting a total of 11 bibliographic sources in English and Spanish from the last 5 years. Results: the results reveal that polypharmacy is more common in women and vulnerable people, generating health and quality of life problems. Drug interactions can be potentiated or inhibited, negatively affecting treatment. Globally, the use of medications in older adults has increased, with the prevalence of polypharmacy varying between countries. In Cuba, it is frequent and age-related, posing challenges in geriatrics. Associated symptoms range from cognitive problems to falls and dizziness, and studies suggest a link between polypharmacy and higher mortality rates. The adverse effects of medications can be misinterpreted, affecting functionality and quality of life. Conclusions: polypharmacy in older adults is a global health problem that requires personalized prescriptions and monitoring of adverse reactions. Prioritizing non-drug treatments is essential, implementing specific criteria to improve quality of life and reduce medical complications., La polifarmacia en adultos mayores representa un desafío global en salud pública, especialmente en el uso de psicofármacos, requiriendo una gestión más efectiva para asegurar tratamientos óptimos y minimizar riesgos asociados. Métodos: Este estudio descriptivo se basó en el análisis documental de fuentes bibliográficas de Scielo, Medigraphic, Scopus, Science Direct, PubMed y Elsevier, con énfasis en la polineuropsicofarmacia en la población geriátrica. Además, la organización bibliográfica se realizó a través del gestor Mendeley y se utilizaron los descriptores “polifarmacia” y “persona mayor”, obtenidos de la categoría Ciencias de la Salud, seleccionando un total de 11 fuentes bibliográficas en inglés y español de los últimos 5 años. Resultados: los resultados revelan que la polifarmacia es más común en mujeres y personas vulnerables, generando problemas de salud y calidad de vida. Las interacciones medicamentosas pueden potenciarse o inhibirse, afectando negativamente el tratamiento. A nivel global, el uso de medicamentos en adultos mayores ha aumentado, variando la prevalencia de polifarmacia entre países. En Cuba, es frecuente y relacionado con la edad, planteando desafíos en geriatría. Los síntomas asociados van desde problemas cognitivos hasta caídas y mareos, y estudios sugieren una relación entre polifarmacia y tasas de mortalidad más altas. Los efectos adversos de los medicamentos pueden malinterpretarse, afectando la funcionalidad y calidad de vida. Conclusiones: la polifarmacia en adultos mayores es un problema mundial de salud que requiere prescripciones personalizadas y monitoreo de reacciones adversas. Priorizar tratamientos no medicamentosos es esencial, implementando criterios específicos para mejorar la calidad de vida y reducir complicaciones médicas.

Purpose of review This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined. Recent findings Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex. Summary Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting.

Breast cancer is the most frequently diagnosed malignancy in women. Tamoxifen is the adjuvant drug of choice in the endocrine treatment of estrogen receptor-positive breast cancer. It has effects that are very useful with respect to the vaginal epithelium and bone, in addition, it is cardioprotective. On the other hand, it should be noted that after the diagnosis of the disease, there are notable physical and psychological changes that have a great impact on the patient and that, in many cases, is linked to the appearance of depression. The aim of this work was to analyze the evidence regarding the possible interactions between tamoxifen and different antidepressants, as well as their adverse effects in breast cancer patients receiving tamoxifen treatment. For this, a systematic review of the articles published in the last 10 years in the Science Direct, Dialnet, Scielo, Medigraphic and PubMed databases was carried out. After the final selection of 12 documents, the results indicate that the choice of antidepressant in the case of women with breast cancer undergoing treatment with tamoxifen should be made based on the profile, side effects, and possible drug interaction potential. It is essential to pay special attention to the importance of the interactions that can occur between tamoxifen and antidepressants, since this interaction can have an impact on the prognosis of breast cancer and the indication of antidepressants arises from non-oncology specialists. In short, it is essential to take into account that there is no clinical evidence that supports prescribing one antidepressant instead of another with respect to their efficacy and safety, therefore attention must be paid to the different interactions that may arise., El cáncer de mama constituye el tumor maligno diagnosticado con más frecuencia en mujeres. El tamoxifeno es la droga adyuvante de elección en el tratamiento endocrino del cáncer de mama con receptores estrogénicos positivos. Posee efectos que resultan muy útiles con respecto al epitelio vaginal y el hueso, además, es cardioprotector. Por otra parte, cabe señalar que después del diagnóstico de la enfermedad, se producen notables alteraciones físicas y psicológicas que tienen un gran impacto en la paciente y que, en muchos casos, se vincula a la aparición de depresión. El objetivo principal de este trabajo fue analizar la evidencia en relación con las posibles interacciones entre el tamoxifeno y distintos antidepresivos, así como sus efectos adversos en pacientes de cáncer de mama en tratamiento con tamoxifeno. Para ello, se llevó a cabo una revisión sistemática de los artículos publicados en los últimos 10 años en las bases de datos Science Direct, Dialnet, Scielo, Medigraphic y PubMed. Tras la selección final de 12 documentos, los resultados señalan la elección de antidepresivo en el caso de mujeres con cáncer de mama en tratamiento con tamoxifeno debe realizarse atendiendo al perfil, los efectos secundarios y el potencial de interacción medicamentoso posible. Es fundamental prestar especial atención a la importancia que tienen las interacciones que se pueden producir entre el tamoxifeno y los antidepresivos, puesto que dicha interacción puede repercutir en el pronóstico del cáncer de mama y la indicación de los antidepresivos surge de parte de especialistas no oncológicos. En definitiva, es fundamental tener en consideración que no hay evidencia clínica que secunde prescribir un antidepresivo en lugar de otro con respecto a la eficacia y la seguridad de los mismos, por ello se debe prestar atención a las diferentes interacciones que puedan surgir.

Background: Psychosis is considered a mental disorder characterized by loss of contact with reality. Antipsychotics are a group of very effective medications for the treatment of psychotic episodes. Objective: Recognize adverse cutaneous reactions of antipsychotic drugs Methodology: Bibliographic search in Spanish and English for the most relevant information in the databases pubmed, scielo, medline, national and international libraries specialized in the topics discussed in this review article. Results: 13 articles were found that generally demonstrate that the most frequent cutaneous adverse effects of antipsychotic medications include: exanthematous eruptions, changes in skin pigmentation, photosensitivity, urticaria, pruritus, pigmentation problems, acne, alopecia, fixed drug eruptions and lichenoid reactions. Conclusion: Adverse cutaneous reactions to antipsychotics are rare, most skin lesions are benign and easy to treat. However, more prospective studies are needed in people from different groups to comprehensively confirm such reactions., Antecedentes: La psicosis es considerada un trastorno de la mente caracterizado por la pérdida de contacto con la realidad. Los antipsicóticos son un grupo de medicamentos muy eficaces para el tratamiento de los episodios psicóticos. Objetivo: Reconocer las reacciones adversas cutáneas de los fármacos antipsicóticos Metodología: Búsqueda bibliográfica en español e inglés de la información más relevante en las bases de datos pubmed, scielo , medline, bibliotecas nacionales e internacionales especializadas en los temas tratados en el presente artículo de revisión. Resultados: Se encontraron 13 artículos de los de forma general demuestran que los efectos adversos cutáneos más frecuentes de los medicamentos antipsicóticos incluyen: erupciones exantemáticas, cambios en la pigmentación de la piel, fotosensibilidad, urticaria, prurito, los problemas de pigmentación, el acné, la alopecia, las erupciones fijas por fármacos y las reacciones liquenoides. Conclusión: Las reacciones adversas cutáneas por antipsicóticos son poco frecuentes, la mayoría de las lesiones cutáneas son benignas y fáciles de tratar. Sin embargo, se necesitan más estudios prospectivos en personas de diferentes grupos para confirmar de manera global tales reacciones.

Background: Psychosis is considered a mental disorder characterized by loss of contact with reality. Antipsychotics are a group of very effective medications for the treatment of psychotic episodes. Objective: Recognize adverse cutaneous reactions of antipsychotic drugs Methodology: Bibliographic search in Spanish and English for the most relevant information in the databases pubmed, scielo, medline, national and international libraries specialized in the topics discussed in this review article. Results: 13 articles were found that generally demonstrate that the most frequent cutaneous adverse effects of antipsychotic medications include: exanthematous eruptions, changes in skin pigmentation, photosensitivity, urticaria, pruritus, pigmentation problems, acne, alopecia, fixed drug eruptions and lichenoid reactions. Conclusion: Adverse cutaneous reactions to antipsychotics are rare, most skin lesions are benign and easy to treat. However, more prospective studies are needed in people from different groups to comprehensively confirm such reactions., Antecedentes: La psicosis es considerada un trastorno de la mente caracterizado por la pérdida de contacto con la realidad. Los antipsicóticos son un grupo de medicamentos muy eficaces para el tratamiento de los episodios psicóticos. Objetivo: Reconocer las reacciones adversas cutáneas de los fármacos antipsicóticos Metodología: Búsqueda bibliográfica en español e inglés de la información más relevante en las bases de datos pubmed, scielo , medline, bibliotecas nacionales e internacionales especializadas en los temas tratados en el presente artículo de revisión. Resultados: Se encontraron 13 artículos de los de forma general demuestran que los efectos adversos cutáneos más frecuentes de los medicamentos antipsicóticos incluyen: erupciones exantemáticas, cambios en la pigmentación de la piel, fotosensibilidad, urticaria, prurito, los problemas de pigmentación, el acné, la alopecia, las erupciones fijas por fármacos y las reacciones liquenoides. Conclusión: Las reacciones adversas cutáneas por antipsicóticos son poco frecuentes, la mayoría de las lesiones cutáneas son benignas y fáciles de tratar. Sin embargo, se necesitan más estudios prospectivos en personas de diferentes grupos para confirmar de manera global tales reacciones.

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

Drug–drug interactions (DDIs) between warfarin (WF) and fluoropyrimidines are well known. Co-administration of WF and 5-fluorouracil (5-FU) leads to elevations in prothrombin time international normalised ratio (PT-INR). The inhibition of drug metabolism through suppression of CYP activity is a possible cause of prolonged PT-INR elevations. 5-FU and its metabolites are suspected to inhibit CYPs, but the precise mechanisms of action remain unknown. This study aimed to investigate the possible DDI effects of the co-administration of 5-FU with WF using PT-INR and PT-INR/dose ratio as pharmacodynamic parameters. Retrospective case series data were collected from patients who received parenteral 5-FU chemotherapy from April 2009 to December 2019 at the University of the Ryukyus Hospital. Seven patients who received 5-FU in combination with WF were analysed. There was a significant increase in PT-INR and PT-INR/dose during the co-administration of WF and 5-FU (p= 0.0018 and p= 0.0187, respectively; paired t-test). The findings demonstrated significant DDI between 5-FU and WF evident as elevated PT-INR and PT-INR/dose ratio.

Drug–drug interactions (DDIs) between warfarin (WF) and fluoropyrimidines are well known. Co-administration of WF and 5-fluorouracil (5-FU) leads to elevations in prothrombin time international normalised ratio (PT-INR). The inhibition of drug metabolism through suppression of CYP activity is a possible cause of prolonged PT-INR elevations. 5-FU and its metabolites are suspected to inhibit CYPs, but the precise mechanisms of action remain unknown. This study aimed to investigate the possible DDI effects of the co-administration of 5-FU with WF using PT-INR and PT-INR/dose ratio as pharmacodynamic parameters. Retrospective case series data were collected from patients who received parenteral 5-FU chemotherapy from April 2009 to December 2019 at the University of the Ryukyus Hospital. Seven patients who received 5-FU in combination with WF were analysed. There was a significant increase in PT-INR and PT-INR/dose during the co-administration of WF and 5-FU (p= 0.0018 and p= 0.0187, respectively; paired t-test). The findings demonstrated significant DDI between 5-FU and WF evident as elevated PT-INR and PT-INR/dose ratio.

[No abstract available]

[No abstract available]

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

The potential for drug-drug interactions (pDDIs) is higher with cardiac medications, and reports of pDDIs in cardiovascular patients are more common. Multimorbidity, a greater number of drugs prescribed, longer hospital stays, complexity of disease, physiological changes with advancing age or conditions like renal failure, shock, hepatic disease like cirrhosis or acute viral hepatitis, stages of disease, and the influence of heart disease on drug metabolism make patients with CVD especially susceptible to DDIs. Our research found that pDDIs occurred at a much higher rate than expected in the Cardiology Division. Incidence of pDDIs was observed to rise with age, polypharmacy, and duration of hospital stay; pDDIs were also more common in males than females. Most of the interactions were of a pharmacodynamic character and were considered to be quite serious. Most pDDIs involved aspirin and clopidogrel, then aspirin and enalapril, and finally enalapril and enalapril. The surveillance of pDDIs in cardiac inpatients may benefit from the creation of such a database in hospitals.

Background: Patients with cancer are managed across the whole healthcare spectrum. This complex system of interdependencies has high potential for errors to occur. This is a focus area for pharmacists, who possess the skillset to optimise cancer care across the health care system, identifying errors and other medication-related problems (MRP). Aim(s): The aim of this study was to identify and describe the impact of the pharmacist's contribution in reducing cancer therapy-related errors. Method(s): A search of English-language publications in Embase, Medline and CINAHL was conducted. Databases were searched from 1 January 2010 until 29 September 2020 to identify all quantitative studies of a descriptive, observational or experimental design. Articles describing pharmacist-led interventions in adults receiving one or more cancer therapies including oral chemotherapy, intravenous chemotherapy or immunotherapy compared to no intervention, usual care or a service delivered by another healthcare professional were included. Researchers screened articles to identify eligible studies, and then data were extracted using a standardised data collection sheet. Quality assessment was undertaken using the modified Cochrane and the Newcastle Ottawa risk of bias tools. Data were reported as number or percentage. Result(s): Of 2292 papers identified, nine studies were eligible for inclusion in this review. Pharmacist interventions consistently showed an increased identification of medication errors and medication-related problems. Pharmacist contributions in many of the included studies comprised medication reviews and monitoring, laboratory monitoring, adverse drug reaction and drug-drug interaction management, adherence monitoring and medication counselling. All studies showed pharmacist intervention in cancer care resulted in fewer errors compared to control arms. Error minimisation was described for parenteral and oral cancer therapies and also for supportive medications such as

Background: Patients with cancer are managed across the whole healthcare spectrum. This complex system of interdependencies has high potential for errors to occur. This is a focus area for pharmacists, who possess the skillset to optimise cancer care across the health care system, identifying errors and other medication-related problems (MRP). Aim(s): The aim of this study was to identify and describe the impact of the pharmacist's contribution in reducing cancer therapy-related errors. Method(s): A search of English-language publications in Embase, Medline and CINAHL was conducted. Databases were searched from 1 January 2010 until 29 September 2020 to identify all quantitative studies of a descriptive, observational or experimental design. Articles describing pharmacist-led interventions in adults receiving one or more cancer therapies including oral chemotherapy, intravenous chemotherapy or immunotherapy compared to no intervention, usual care or a service delivered by another healthcare professional were included. Researchers screened articles to identify eligible studies, and then data were extracted using a standardised data collection sheet. Quality assessment was undertaken using the modified Cochrane and the Newcastle Ottawa risk of bias tools. Data were reported as number or percentage. Result(s): Of 2292 papers identified, nine studies were eligible for inclusion in this review. Pharmacist interventions consistently showed an increased identification of medication errors and medication-related problems. Pharmacist contributions in many of the included studies comprised medication reviews and monitoring, laboratory monitoring, adverse drug reaction and drug-drug interaction management, adherence monitoring and medication counselling. All studies showed pharmacist intervention in cancer care resulted in fewer errors compared to control arms. Error minimisation was described for parenteral and oral cancer therapies and also for supportive medications such as

Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.

Background: Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Methods: This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool's HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients' preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired Results: Among 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, -1.1 to -0.8) after patients switched to BIC/FTC/TAF ( Conclusions: Treatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF.

Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.

Single-tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high-income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV-related neurological disease, or associated opportunistic infections, which include co-infections, and primarily age- and lifestyle-related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR - bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) - in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co-infection; HLA-B*5701 status; drug-drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence-friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non-inferior to dolutegravir-based regimens previously recommended by most guidelines for treatment initiation in large double-blind, randomised clinical trials in treatment-naive or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.Copyright © 2020 British HIV Association

Single-tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high-income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV-related neurological disease, or associated opportunistic infections, which include co-infections, and primarily age- and lifestyle-related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR - bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) - in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co-infection; HLA-B*5701 status; drug-drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence-friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non-inferior to dolutegravir-based regimens previously recommended by most guidelines for treatment initiation in large double-blind, randomised clinical trials in treatment-naive or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.Copyright © 2020 British HIV Association

The potential to interaction of herbal medicines with Oral Anticoagulants (OACs) and Antiplatelet (AAPs) drugs is a concern for health professionals today. Factors such as age, polymedication or genetic polymorphisms can favor the appearance of interactions or the worsening of adverse reactions. Objectives: Detect potential interactions between herbal medicines and synthetic drugs in patients at Pharmacy Offices in the Seville metropolitan area, as well as document and discuss their possible relevance considering risk factors according to the data provided in the Bibliography and the patients potentially involved. Material and Methods: search in monographs EMA (European Medicines Agency) and ESCOP (European Scientific Cooperative On Phytotherapy), Phytotherapy Books and Manuals and Databases. Application of an anonymous questionnaire on the use of medicinal plants in Pharmacy Office patients. Results: as a consequence of the bibliographic review, 26 herbal drugs have been selected, of which only 9 have potential interactions described in the reference monographs EMA and ESCOP. For some drugs, such as ginkgo leaf, many studies are available and have shown their potentiating effects on antiplatelet activity, while others such as ginseng root show more contradictory results. Studies on the influence of genetic polymorphisms in pharmacodynamic pathways on the result of the interaction are also available on the cranberry fruit and the garlic bulb. 21,4% (n = 54) of the patients surveyed in the Pharmacy Offices consumed some of these herbal medicines. Four cases of potential interactions were detected, based on a possible increase in INR and risk of bleeding, with risk factors such as advanced age (> 70 years), daily use of herbal medicine and polypharmacy. Conclusion: the available evidence must be taken into account in clinical practice and in future studies, taking extreme precautions when associating these drugs, despite the fact that in some cases the causality of th, El potencial de interacción de los fitoterápicos con fármacos Anticoagulantes Orales (ACOs) y Antiagregantes plaquetarios (AAPs) supone una preocupación para los profesionales de la salud en la actualidad. Factores como la edad, la polimedicación o los polimorfismos genéticos pueden favorecer la aparición de interacciones o el agravamiento de reacciones adversas. Objetivos: Detectar potenciales interacciones entre fitoterápicos y fármacos de síntesis en pacientes de Oficinas de farmacia del área metropolitana de Sevilla, así como documentar y discutir su posible relevancia considerando factores de riesgo de acuerdo con los datos aportados en Bibliografía y los pacientes potencialmente implicados. Material y Métodos: Búsqueda en monografías EMA (European Medicines Agency) y ESCOP (European Scientific Cooperative On Phytotherapy), Libros y Manuales de Fitoterapia y Bases de datos. Aplicación de un cuestionario anónimo sobre el uso de plantas medicinales en los pacientes de Oficina de Farmacia. Resultados: Consecuencia de la revisión bibliográfica, se han seleccionado 26 drogas vegetales, de las cuales sólo 9 tienen descritas interacciones potenciales en las monografías de referencia EMA y ESCOP. De algunas drogas, como la hoja de ginkgo, se dispone de muchos estudios y se han demostrado sus efectos potenciadores de la actividad antiagregante, mientras que otras como la raíz de ginseng muestran resultados más contradictorios. Del fruto de arándano rojo y el bulbo de ajo se dispone además de estudios sobre la influencia de los polimorfismos genéticos en vías farmacodinámicas sobre el resultado de la interacción. El 21,4% (n=54) de los pacientes encuestados en las Oficinas de Farmacia consumía alguno de estos fitoterápicos. Se detectaron 4 casos de interacciones potenciales, basadas en un posible aumento del INR y riesgo de hemorragias, concurriendo en estos pacientes factores de riesgo como edad avanzada (>70 años), consumo diario del fitoterápico y polimedicación. Conc

We present a CRISPR-based multi-gene knockout screening system and toolkits for extensible assembly of barcoded high-order combinatorial guide RNA libraries en masse. We apply this system for systematically identifying not only pairwise but also three-way synergistic therapeutic target combinations and successfully validate double- and triple-combination regimens for suppression of cancer cell growth and protection against Parkinson's disease-associated toxicity. This system overcomes the practical challenges of experimenting on a large number of high-order genetic and drug combinations and can be applied to uncover the rare synergistic interactions between druggable targets. © 2020 The Author(s); Studying high-order druggable gene interactions that mimic the actions of targeted drug combinations is practically challenging. Zhou et al. describe an extensible CombiGEM-CRISPR system for screening high-order combinations, leading to identification of double- and triple-combination regimens that suppress ovarian cancer growth and Parkinson's disease-associated toxicity. © 2020 The Author(s)

Aims: To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is). Methods: The FDA adverse event reporting system (FAERS) was queried (2004–2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug–drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed). Results: Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96–1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42–1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62–0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors. Conclusions: Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.

Doravirine (DOR) is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus‐1 (HIV‐1). Its use in combination with rifapentine (RPT), an anti‐tuberculosis antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV‐1 co‐infected with tuberculosis. We conducted a prospective, phase I, open label, two‐period, fixed sequence, drug interaction study to evaluate the effect of once‐weekly RPT and isoniazid (INH) on the pharmacokinetics of DOR in healthy volunteers. DOR 100 mg was administered alone twice‐daily for 4 days in period 1. In period 2, once‐weekly RPT+INH was co‐administered with multiple doses of DOR 100 mg twice‐daily for study days 7, 14, and 21. Plasma was obtained for DOR pharmacokinetics when given alone and co‐administered with RPT+INH. Eleven healthy volunteers enrolled and completed the study. The geometric mean ratios and 90% confidence intervals for DOR AUC0‐12 and C12 in the presence of RPT+INH compared to DOR alone were 0.71 (0.60‐0.85) and 0.69 (0.54‐0.89), respectively. Although exposures were moderately reduced in the presence of RPT+INH, trough DOR values were within the concentration range associated with virological suppression. These results demonstrate that a modest decrease in doravirine exposure would unlikely be clinically relevant in a virally suppressed patient co‐administered once‐weekly RPT+INH.

In this thesis we aimed to further explore the relevance of dosing algorithms for VKAs compared to standard dosing and how these algorithms perform in different age groups. We also aimed to evaluate the influence of drug interactions on the safety of DOACs in daily clinical practice and whether health care practitioners take into account drug interactions when deciding on the prescribed dose of DOACs. We also study the cost-effectiveness of a variety of clinical and genotype-guided dosing algorithms for VKAs versus DOACs. In Chapter 2, a study is presented in which we compared the anticoagulant effect of dosing algorithms for acenocoumarol and phenprocoumon including clinical patient characteristics with standard care in the Netherlands. Chapter 3 describes a study in which we compared the effect of genotype-guided dosing of acenocoumarol or phenprocoumon in younger and older patients. Chapter 4 of this thesis focuses on the influence of drug interactions on the safety of DOACs. We conducted a case control study in the UK Clinical Practice Research Datalink to investigate the association between concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs and major bleeding among DOAC users. In Chapter 5, we describe the frequency of adjustments of DOAC treatment including dose adjustment, discontinuation of use, and switching to a VKA when interacting drugs were concomitantly used. In Chapter 6, we assessed the cost-effectiveness of DOACs versus different clinical and genotype-guided dosing algorithms for acenocoumarol and phenprocoumon as well as standard care in Dutch patients with atrial fibrillation. Finally, in Chapter 7, we summarize our main findings and discuss them in a broader perspective, discuss strengths and limitations and present recommendations for daily practice and further research. Our studies contribute to the knowledge on factors that influence the benefit risk of those oral anticoagulants and thereby will contribute to the

This research employs text and data mining methods to gain valuable knowledge for human drugs. Specifically, computational methods are developed for three topics, namely drug-side-effect prediction, drug-target identification, and drug-drug-interaction detection. The key innovations of the proposed methods lie in the feature space construction using medical domain knowledge, generation of reliable negative samples, and successful application of machine learning algorithms. The drug-side-effect prediction problems are studied in Chapters 3-5. Side-effects are secondary phenotypic responses of human organisms to drug treatments. Side-effect prediction is an important topic for drugs especially in post-marketing surveillance because they cause significant fatality and severe morbidity. To overcome the limitations of existing computational methods such as lack of proper drug representation and reliable negative samples, this thesis presents three novel methods. The first method is to predict side-effects for single drug medication as described in Chapter 3. A comprehensive drug similarity framework is developed by integrating several types of similarities measured by representative features of drugs first. Then reliable negative samples are generated through analyzing the comprehensive drug similarities. Trained with generated reliable negatives, the prediction performance of four classical classifiers are improved significantly, outperforming those state-of-the-art methods. Chapter 4 describes the method proposed to predict side-effects for combined medication of multi-drugs. A scoring method on a drug-disease-gene tripartite network is developed to prioritize interacting drugs, paving a way to generate credible negative samples for side-effect prediction of combined medication. It creatively characterized a drug with its chemical structures, target proteins, substituents, and enriched pathways. The drug-drug pairs are represented as novel feature vectors to train bina

Environmental stressors come in many different forms and affect every level of ecological organization. In a natural environment, organisms experience mixtures of stressors at various doses or strengths of exposure that could be constantly changing, both temporally and spatially. Complex environmental regimes and interactions among multiple stressors can have a profound effect on both the short-term fitness of organisms and their long-term evolutionary dynamics. This dissertation uses a bacterium-drug system to study drug-drug, drug-temperature, and gene-gene interactions. The first question we ask is how bacteria evolve to combat new stressors. Through an interaction network clustering approach followed by transcriptomic analysis, we show that Escherichia coli may have co-opted its cellular response to temperature stress for antibiotic stress because these stressors share similar physiological effects. We also found that antibiotic stress modifies the thermal response of E. coli by altering both its optimal growth temperature and temperature breadth. Next, we ask how we can identify and quantify dose-dependent drug interactions, including interactions among more than two components, i.e., higher-order interactions. To do this, we introduce a novel visual representation termed interaction landscape to directly map local dose-dependent interactions and the transitions between different interaction classes. Finally, we ask how gene-gene interactions change in fluctuating environments. We showed that changes in the type and magnitude of environmental fluctuations could affect fitness due to the differences in epistatic interactions of mutations. We quantify structural features of fitness landscapes by calculating the ruggedness across broad concentration gradients of various antibiotics. We show that fluctuating environments frequently lead to epistasis sign switches (from negative to positive or vice versa) on the pairwise level, as a potential mechanism to either pro

This research employs text and data mining methods to gain valuable knowledge for human drugs. Specifically, computational methods are developed for three topics, namely drug-side-effect prediction, drug-target identification, and drug-drug-interaction detection. The key innovations of the proposed methods lie in the feature space construction using medical domain knowledge, generation of reliable negative samples, and successful application of machine learning algorithms. The drug-side-effect prediction problems are studied in Chapters 3-5. Side-effects are secondary phenotypic responses of human organisms to drug treatments. Side-effect prediction is an important topic for drugs especially in post-marketing surveillance because they cause significant fatality and severe morbidity. To overcome the limitations of existing computational methods such as lack of proper drug representation and reliable negative samples, this thesis presents three novel methods. The first method is to predict side-effects for single drug medication as described in Chapter 3. A comprehensive drug similarity framework is developed by integrating several types of similarities measured by representative features of drugs first. Then reliable negative samples are generated through analyzing the comprehensive drug similarities. Trained with generated reliable negatives, the prediction performance of four classical classifiers are improved significantly, outperforming those state-of-the-art methods. Chapter 4 describes the method proposed to predict side-effects for combined medication of multi-drugs. A scoring method on a drug-disease-gene tripartite network is developed to prioritize interacting drugs, paving a way to generate credible negative samples for side-effect prediction of combined medication. It creatively characterized a drug with its chemical structures, target proteins, substituents, and enriched pathways. The drug-drug pairs are represented as novel feature vectors to train bina

A 68-year-old man develops acute hepatocellular injury during treatment with direct-acting antiviral agents (DAA) for hepatitis C. Medical history reveals the intake of tamoxifen as adjuvant treatment for breast cancer, currently in remission. After stopping tamoxifen, despite the continuation of the anti-HCV agents, a complete resolution of liver injury occurs. This interesting case illustrates tamoxifen hepatotoxicity induced by CYP3A4 interaction with direct anti-HCV agents. It stresses the importance of checking for interactions before starting treatment for hepatitis C.

Environmental stressors come in many different forms and affect every level of ecological organization. In a natural environment, organisms experience mixtures of stressors at various doses or strengths of exposure that could be constantly changing, both temporally and spatially. Complex environmental regimes and interactions among multiple stressors can have a profound effect on both the short-term fitness of organisms and their long-term evolutionary dynamics. This dissertation uses a bacterium-drug system to study drug-drug, drug-temperature, and gene-gene interactions. The first question we ask is how bacteria evolve to combat new stressors. Through an interaction network clustering approach followed by transcriptomic analysis, we show that Escherichia coli may have co-opted its cellular response to temperature stress for antibiotic stress because these stressors share similar physiological effects. We also found that antibiotic stress modifies the thermal response of E. coli by altering both its optimal growth temperature and temperature breadth. Next, we ask how we can identify and quantify dose-dependent drug interactions, including interactions among more than two components, i.e., higher-order interactions. To do this, we introduce a novel visual representation termed interaction landscape to directly map local dose-dependent interactions and the transitions between different interaction classes. Finally, we ask how gene-gene interactions change in fluctuating environments. We showed that changes in the type and magnitude of environmental fluctuations could affect fitness due to the differences in epistatic interactions of mutations. We quantify structural features of fitness landscapes by calculating the ruggedness across broad concentration gradients of various antibiotics. We show that fluctuating environments frequently lead to epistasis sign switches (from negative to positive or vice versa) on the pairwise level, as a potential mechanism to either pro

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. The current study evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin-3-gallate, theaflavin-3 '-gallate and theaflavin-3,3 '-digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (C-max) and area under the plasma concentration-time curve (AUC(0)-(8)) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1-mediated rosuvastatin and estrone-3-sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of V-max/K-m) of rosuvastatin was decreased following treatment with TFs. Black tea extracts also reduced OATP2B1-mediated rosuvastatin uptake. These results suggest that black tea reduces the plasma concentrations of rosuvastatin by inhibiting the intestinal OATP2B1-mediated transport of rosuvastatin.

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. The current study evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin-3-gallate, theaflavin-3 '-gallate and theaflavin-3,3 '-digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (C-max) and area under the plasma concentration-time curve (AUC(0)-(8)) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1-mediated rosuvastatin and estrone-3-sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of V-max/K-m) of rosuvastatin was decreased following treatment with TFs. Black tea extracts also reduced OATP2B1-mediated rosuvastatin uptake. These results suggest that black tea reduces the plasma concentrations of rosuvastatin by inhibiting the intestinal OATP2B1-mediated transport of rosuvastatin.

Modern antiretroviral therapy (ART) extends life expectancy for people living with HIV (PLWH). However, most older PLWH (≥50 years) "aged" with HIV and were exposed to historical HIV care practices and older, more toxic ART. In PLWH with exposure to older and multiple ART regimens, the drug interactions between ART frequently used in treatment-experienced persons and commonly used immunosuppressants remain a significant challenge. However, the advent of newer ART classes (eg, integrase non-strand transfer inhibitors) and more advanced HIV genetic resistance testing may allow optimization of ART regimens with minimal drug interactions. Here, we present a case series of three PLWH whose complicated ART interacted (or was at risk for interacting) with their post-liver transplant immunosuppression. After a review of their proviral DNA resistance testing, they successfully transitioned onto safer integrase non-strand transfer inhibitor-containing ART regimens without viral blips or evidence of organ rejection.

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. The current study evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin-3-gallate, theaflavin-3 '-gallate and theaflavin-3,3 '-digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (C-max) and area under the plasma concentration-time curve (AUC(0)-(8)) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1-mediated rosuvastatin and estrone-3-sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of V-max/K-m) of rosuvastatin was decreased following treatment with TFs. Black tea extracts also reduced OATP2B1-mediated rosuvastatin uptake. These results suggest that black tea reduces the plasma concentrations of rosuvastatin by inhibiting the intestinal OATP2B1-mediated transport of rosuvastatin.

Background: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD). Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation. Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)). Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Current guidelines recommend caution in prescribing concomitant use of direct-acting oral anticoagulants (DOACs) and antiepileptic drugs due to drug–drug interactions leading to potential risk of DOACs subtherapeutic concentration and treatment failure. Herein we report a significant interaction between carbamazepine (CZP) and apixaban, causing subtherapeutic concentration of the drug in a patient with atrial fibrillation who had a transient ischemic attack (TIA) episode. Another anti-Xa DOAC, edoxaban, administered to the patient after TIA occurrence did not show significant interaction with CZP. In addition to confirm that cautions should be used when antiepileptic and DOACs are concomitantly prescribed, the present case also demonstrates that, in the management of certain subsets of patients who need anticoagulant treatment, measurement of DOAC plasma concentration can help guide a personalized management and avoid adverse clinical outcomes.

Idiopathic pulmonary fibrosis (IPF) is a progressivediseasewithamediansurvivalof 3–5 years (1, 2). The approval of nintedanib and pirfenidone by regulatory agencies worldwide has dramatically altered the landscape for testing new drugs for IPF treatment. These drugs slowed the progression of the FVC decline observed in IPF cohorts in phase III randomized, double-blind, placebo-controlled trials (3, 4).

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Società Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0–9.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients.

High rate of cardiovascular morbidity dictates the need for wide use of antithrombotic agents in clinical practice. Therapy which based on drugs with different mechanisms of action on the thrombocytic component of homeostasis appears to be especially promising as having synergic antiplatelet effect. The most common antiplatelet therapy is a combination of acetylsalicylic acid and clopidogrel usually referred to as a dual antiplatelet therapy (DAT). Current consensus recommends intake of proton pump inhibitors (PPI) during DAT to reduce the risk of gastrointestinal complications. However, recent studies showed that this approach is associated with severe cardiovascular disorders, such as myocardial infarction, stroke, unstable angina, necessity of coronary interventions, and coronary death. So, it seems to be important to develop strategies for the differential use of PPI in patients receiving DAT. The article presents the reviews of the literature on the above issues with the results of studies of various PPI effect on clinical outcomes in patients taking clopidogrel., Высокая заболеваемость и смертность от сердечно-сосудистых заболеваний привели к необходимости широкого использования антитромбоцитарных средств в клинической практике. Наиболее перспективной представляется комбинированная антиагрегантная терапия с использованием препаратов, имеющих разные механизмы влияния на тромбоцитарное звено гемостаза, за счет чего можно добиться выраженного синергического эффекта. В нашей стране преимущественно назначается комбинация ацетилсалициловой кислоты и клопидогреля, которую часто называют двойной антитромбоцитарной терапией (ДАТ). Для уменьшения рисков развития желудочно-кишечных осложнений при использовании ДАТ рекомендован прием ингибиторов протонной помпы (ИПП), однако в некоторых исследованиях упоминается, что одновременное назначение ИПП и клопидогреля в перспективе повышает риск возникновения неблагоприятных сердечно-сосудистых событий, к которым относятся инфаркт миокарда, инсульт, нестабильная стенокардия, необходимость повторных коронарных вмешательств и коронарная смерть. В связи с этим представляется актуальной выработка подходов дифференцированного применения ИПП у пациентов, получающих ДАТ. Представлен обзор литературы по обозначенной выше проблематике, приведены результаты исследований по изучению влияния различных ИПП на клинические исходы у больных, принимающих клопидогрель., Висока захворюваність і смертність від серцево-судинних захворювань призвели до необхідності широкого використання антитромбоцитарних засобів у клінічній практиці. Найбільш перспективною вважається комбінована антиагрегантна терапія з використанням препаратів, що мають різні механізми впливу на тромбоцитарну ланку гемостазу, за рахунок чого можна досягти вираженого синергічного ефекту. У нашій країні переважно призначається комбінація ацетилсаліцилової кислоти і клопідогрелю, яку часто називають подвійною антитромбоцитарною терапією (ПАТ). Для зменшення ризиків розвитку шлунково-кишкових ускладнень при використанні ПАТ рекомендований прийом інгібіторів протонної помпи (ІПП), проте в деяких дослідженнях згадується, що одночасне призначення ІПП та клопідогрелю в перспективі підвищує ризик виникнення несприятливих серцево-судинних подій, до яких відносять інфаркт міо-карда, інсульт, нестабільну стенокардію, необхідність повторних коронарних втручань і коронарну смерть. У зв’язку з цим представляється актуальною проблема розробки підходів диференційованого застосування ІПП у пацієнтів, які отримують ПАТ. Надано огляд літератури з означеної вище проблематики, наведено результати досліджень із вивчення впливу різних ІПП на клінічні наслідки у хворих, які приймають клопі-догрель.

Drug interactions are the result of co-administration of several drugs. The present study aimed to identify the animal populations that have the greatest exposure to polypharmacy in veterinary clinics located in urban areas of the province of Heredia,Costa Rica, as well as the report of the main pharmacological interactions registered inn these. It was found that the canine species is the one that comes more frequentlyto consultation and in turn is the one that is expo sed more frequently to the polymerization,and this brings with it greater probability of drug interactions. The maindocumented interactions are with antifungals, anti-inflammatories, glucocorticoids,and antibacterials., Las interacciones farmacológicas son el resultado de la administración conjunta de varios medicamentos. El presente trabajo tuvo como objetivo identificar las poblacionesanimales que poseen mayor exposición a la polifarmacia en clínicas veterinari asubi cadas en zonas urbanas de la provincia de Heredia, en Costa Rica; así comoel reporte de las principales interacciones farmacológicas registradas en estas. Seencontró que la especie canina es la que acude con mayor frecuencia a consulta y, a suvez, es la que se expone con mayor frecuencia a la polimedicación, trayendo consigomayor probabilidad de interacciones medicamentosas. Las principales interaccionesdocumentadas son con antifúngicos, antiinflamatorios, glucocorticoides y antibacterianos.

According to the World Health Organization (WHO) adverse reaction called any not sought damaging response occurring at doses normally used in man for the treatment, prophylaxis or diagnosis; as a result, are not considered adverse drug reactions poisonings caused by voluntary or involuntary ingestion of excessive doses of a drug. There are two fundamental types of adverse drug reactions: quantitative type or A type of Augmented, which are common, non-serious, related to the dose and relatively expected or predictable; reactions adverse qualitative or type B Bizarre which are pharmacologically distinct from normal responses and depend on an abnormal reactivity of the sick (idiosyncrasy, hypersensitivity), are relatively uncommon, in general they cannot be predicted or avoided, not related to the dose and tend to be much more severe than type A. Type B reactions or qualitative highlights the bone marrow aplasia independent dose produced by chloramphenicol with an incidence of 1/30000. The following methods are used in the detection of adverse reactions: • Voluntary reporting or yellow card. • Hospital intensive monitoring. • Review of the local medical literature. • Analysis of vital statistics. • Clinical trials. • Case-control studies., Se denomina reacción adversa según la Organización Mundial de la Salud (OMS) cualquier respuesta perjudicial no buscada que aparece a las dosis habitualmente empleadas en el hombre para el tratamiento, profilaxis o diagnóstico; en consecuencia, no se consideran reacciones adversas medicamentosas las intoxicaciones provocadas por la ingestión voluntaria o involuntaria de dosis excesivas de un medicamento. Se distinguen dos tipos fundamentales de reacciones adversas a medicamentos: las de tipo cuantitativo o tipo A de Augmented, que son frecuentes, no graves, relacionadas con la dosis y relativamente esperables o previsibles; las reacciones adversas de tipo cualitativo o de tipo B de Bizarre que son farmacológicamente distintas de las respuestas normales y dependen de una reactividad anormal del enfermo (idiosincrasia, hipersensibilidad), son relativamente poco frecuentes, en general no pueden predecirse ni evitarse, no guardan relación con la dosis y suelen ser mucho más graves que las de tipo A. Entre las reacciones de tipo B o cualitativo destaca la aplasia medular dosis independiente producida por el cloranfenicol con una incidencia de 1/30000. En la detección de reacciones adversas se utilizan los siguientes métodos: • Notificación voluntaria o tarjeta amarilla. • Monitorización intensiva hospitalaria. • Revisión de la literatura médica local. • Análisis de estadísticas vitales. • Ensayos clínicos. • Estudios de casos y controles.

In USA and Europe, more than 50% of adults aged 75 years old or older are taking a lifelong antiplatelet treatment, of which half are for secondary prevention of vascular diseases [1]. The major side effect of the aforementioned therapy is the risk of major bleeding, particularly from the upper gastrointestinal tract. However, clinical guidelines on secondary prevention of vascular events do not recommend proton pump inhibitors (PPIs), which could reduce the incidence of bleeding by 70-90%. This is probably due to the adverse effects of the PPIs, as stated in a recent Mayo Clinic's review [2], and because in aspirin trials, the gastrointestinal bleeds have a low mortality and permanent disability rates. However, most of the populations of the aspirin trials were younger than 75 years of age, and thus, up to now, the agespecific risk of bleeding in patients on long-term antiplatelet treatment after vascular events has not been sufficiently studied