Efecto de los fármacos modificadores del PH sobre los inhibidores de la tirosin quinasa: contrastando información / Effect of gastric-acid-reducing agents on the tyrosine kinasa inhibitors: contrasting information

Objetivos: Los inhibidores de la tirosin quinasa (ITK) comprenden un conjunto de moléculas ampliamente utilizadas actualmente en onco-hematología. Los ITK han supuesto una ventaja para los pacientes, de forma que la administración oral favorece su autonomía, pero a su vez, su absorción gastrointestinal y, por ende, su biodisponibilidad, puede verse alterada por el PH-gástrico. Las interacciones con los fármacos modificadores del PH son un problema conocido y una consulta frecuente. El objetivo del estudio fue analizar las interacciones ITK-fármacos modificadores del PH-gástrico y las discrepancias en diferentes bases de datos. Con los resultados, se elaboró una tabla, para proporcionar a los pacientes la información correcta y consensuada, y no generar así inseguridad que comprometa la adherencia al tratamiento o confianza hacia el profesional sanitario. Métodos: Se exportaron de la web de la Agencia Española del Medicamento y Productos Sanitarios los fármacos clasificados como ITK directos (ATC: L01XE). Se consultó la interacción de éstos con los IBP, Anti-H2 y antiácidos en diversas fuentes y se resumieron los hallazgos.Resultados y conclusiones: Para establecer una fuerte recomendación, es necesario consultar varias bases de datos, ya que las discrepancias o la información insuficiente pueden llevar a recomendaciones erróneas. Es importante establecer un consenso entre profesionales para realizar la recomendación correcta, y no ver comprometida la eficacia del tratamiento, con las importantes consecuencias que ello conllevaría. (AU)

Objectives: Tyrosine kinase inhibitors (TKIs) include a group of molecules widely used in oncohematology today. Using the oral administration route of TKIs offers an advantage for the patient; favoring patient autonomy, however, oral administration also causes relevant new problems. Gastrointestinal absorption and, therefore, bioavailability, can be altered by gastric PH. Interactions of these TKIs with gastric acid reducing (GAR) drugs are a known problem and a frequent query in clinical practice. The aim was to analyze ITK-GAR drugs interactions and discrepancies in different databases. Based on the results, a table was elaborated to provide the correct and consensed information, and thus not generate insecurity that compromises the adherence to the treatment or trust towards the healthcare professional.Methods: Drugs classified as direct ITKs (ATC: L01XE) were exported from the Spanish Agency for Medicines and Health Products website. Their interaction with PPIs, Anti-H2 and antacids was consulted in different databases and findings were summarized.Results and conclusions: To establish a strong recommendation, it is necessary to consult several databases, because of discrepancies or insufficient information can lead to erroneous recommendations. It is important to establish a consensus among professionals to make the correct recommendation, and not compromising the effectiveness of the treatment, which would entail important consequences. (AU)

Monitorización farmacocinética de terapias biológicas en enfermedad inflamatoria intestinal / Pharmacokinetic monitoring of biological therapies in inflammatory bowel disease

Objective: To analyze the activity developed by a multidisciplinary team of pharmacists, digestive specialists and clinical analysts for the therapeutic drug monitoring (TDM) of anti-TNFa therapies in inflammatory bowel disease (IBD).Methods: A prospective observational study (January-December 2019) was conducted of referrals from digestive specialists to the Clinical Pharmacokinetics Unit (CPU) of our general hospital for the TDM of anti-TNFa drugs (infliximab/adalimumab) in adults with IBD. Serum anti-TNFa concentrations were quantified in our Clinical Analysis Laboratory using lateral flow chromatography. When concentrations were undetectable, the presence of anti-drug antibodies (ADAs) was analyzed.CPU recommendations were based on the correct interpretation of anti-TNFa concentrations, therapeutic algorithms, and populational pharmacokinetic models implemented using MW-Pharm++® software. Results: Referrals were received for 84 patients (81.0% with Crohn’s disease, 8.3% with ADAs) treated with infliximab (46.4%) or adalimumab (53.6%); 64.3% were also treated with concomitant immunomodulators (IMMs). Sixty-three referrals (75.0%) were for proactive monitoring (treatment optimization) and the remainder for reactive monitoring after therapeutic failure. Anti-TNFa concentrations were subtherapeutic in 36.9% of patients, therapeutic in 39.3%, and supratherapeutic in 23.8%. Subtherapeutic/undetectable concentrations were significantly more frequent (p≤0.004) in patients treated with infliximab versus adalimumab (64.1% vs.. 13.3%) and in concomitant IMM non-adherents versus adherents (85.7% vs. 25.5%). Conclusions: Anti-TNFa TDM is frequently proactive in patients with IBD. The wide variability in anti-TNFa concentrations is in part explained by the type of anti-TNFa drug and adherence to IMM. (AU)

Objetivo: Analizar la actividad desarrollada por un equipo multidisciplinar formado por farmacéuticos, digestólogos y analistas clínicos para la monitorización farmacocinética (TDM) de terapias anti-TNFa en la enfermedad inflamatoria intestinal (EII).Métodos: Estudio observacional prospectivo (enero–diciembre 2019) de las interconsultas de TDM de anti-TNFa (infliximab/adalimumab) en pacientes adultos con EII, solicitadas por digestólogos a la Unidad de Farmacocinética Clínica (UFC) del Servicio de Farmacia de un hospital general. Las concentraciones séricas (Cs) de anti-TNFa fueron cuantificadas en el Laboratorio de Análisis Clínicos mediante cromatografía de flujo lateral. Cuando las Cs fueron indetectables, se analizó la presencia de anticuerpos anti-fármaco (AAF).La UFC realizó recomendaciones en base a la correcta interpretación de las Cs de anti-TNFa, algoritmos terapéuticos y modelos farmacocinéticos poblacionales implementados en el programa informático de ajuste bayesiano MW-Pharm++®. Resultados: Se solicitaron interconsultas para 84 pacientes (81,0% enfermedad de Crohn, 8,3% AAF positivos) con infliximab (46,4%) ó adalimumab (53,6%). 64,3% recibía otros inmunomoduladores (IMM) concomitantes. 63 interconsultas (75,0%) se relacionaron con monitorización ‘pro-activa’ (optimizar tratamiento); el resto fueron ‘re-activas’ a fallo terapéutico. Se observaron Cs de anti-TNFa subterapéuticas en 36,9% de pacientes, terapéuticas en 39,3% y supraterapéuticas en 23,8%. Las Cs subterapéuticas/indetectables fueron significativamente (p≤0,004) más frecuentes en pacientes tratados con infliximab versus adalimumab (64,1% vs. 13,3%); y en ‘no-adherentes’ versus ‘sí-adherentes’ al IMM concomitante (85,7% vs. 25,5%). Conclusiones: En estos pacientes, la TDM de anti-TNFa es frecuentemente ‘pro-activa’. Existe gran variabilidad en las Cs de anti-TNFa, explicada en parte por el fármaco anti-TNFa y la adherencia al IMM. (AU)

[Central venous catheters-related infections in patients with parenteral nutrition]. / Infecciones relacionadas con el catéter venoso central en pacientes con nutrición parenteral total.

INTRODUCTION: Infections related to central venous catheters (CVC) are complications with a high prevalence and possible serious consequences. Administration of total parenteral nutrition (TPN) is a risk factor, although the information available for these patients and conventional inpatient units is scarce. OBJECTIVE: To determine the rate of catheter-related bacteremia (CRB) in patients with TPN and to identify possible relationships with administration route or place of insertion, to determinate the current situation and identify possible preventive measures. METHOD: Prospective-observational study of 13 months. All adult patients who received TPN were included. Infection rate used was the CRB per 1,000 days of CVC. RESULTS: 176 CVC were registered in 159 patients. In 47% of CVC, vein access was jugular vein, despite being a location of greatest risk of infection. In critically ill patients, which followed a zero bacteremia project, there was no cases of infection. In other patients, bacteremia rate was 13.10 per 1,000 days of CVC. The average time elapsed between catheter insertion and infection was 11 days (range: 4-22) and the most frequent species were S. epidermidis (38%) and S. hominis (19%). DISCUSSION: In our environment there is a high rate of BRC in non-critical patients, with a high proportion of CVC in locations with higher risk of infection, despite not having found in the sample a higher rate of infection depending on the access route. Place of insertion, operating room face ward, is related to a lower rate of BRC. Measures to standardize clinical practice may reduce its incidence. The zero bacteremia project is confirmed as a highly effective method.

[Impact of pharmacotherapeutic warnings on the prescription of clopidogrel and proton pump inhibitors in hospitalised patients]. / Impacto de las alertas farmacoterapéuticas sobre la prescripción de clopidogrel e inhibidores de la bomba de protones en pacientes ingresados.

OBJECTIVE: To estimate the frequency of clopidogrel prescriptions in association with proton pump inhibitors (PPIs) in patients hospitalised with circulatory pathologies, after the publication of several warnings about this association. To identify and quantify the magnitude of the factors related to the prescription of both drugs. METHODOLOGY: Observational, analytical, longitudinal, and retrospective study assessing changes in prescription of clopidogrel-PPIs association after and before the first official warning (about these drugs' interactions) was published. We selected all patients with a code indicating a circulatory system disease in the Minimum Basic Data Set, who had been prescribed clopidogrel during hospital admission. We also evaluated proton pump inhibitor use in these patients (omeprazole and pantoprazole). RESULTS: 5678 patients diagnosed with circulatory diseases were admitted during 2009, and clopidogrel was prescribed in 13.6% of them. In the pre-warning period, clopidogrel-PPIs prescriptions were significantly higher than in the post-warning period (80, 8% vs 48, 6%), especially in omeprazole. The combined prescription was lower if the circulatory diagnosis was the main cause for hospitalisation, if the patient had heart disease, if the patient was admitted in Internal Medicine/Cardiology or Intensive care units, and if the period of time was further from warning. CONCLUSION: Combined prescription has decreased since the first warning, above all in patients with a primary circulatory heart disease. Omeprazole is a potent CYP2C19 inhibitor, so it was used in lower rates than pantoprazole in association with clopidogrel. Medical departments related to cardiovascular disease followed the warning more than others.

[A project for the implementation of a unit-dose drug dispensation system in an intensive care unit]. / Proyecto de implantación del sistema de distribución de medicamentos en dosis unitarias en una unidad de cuidados intensivos.

OBJECTIVE: To describe the implementation of a unitary dose drug dispensation system (UDDDS) with computerized medical orders in an intensive care unit (ICU) including 10 multi-purpose offices, and to obtain a medication error index as an indicator of the process quality. METHOD: A UDDDS with computerized medical orders for intensive care was defined. By consensus among nurses, intensivists and pharmacists, the administration of high-risk drugs by perfusion or through a gastric tube was protocolized, and computerized medical orders were adapted to ICU dynamics, with both fluid therapy and enteral and parenteral nutrition becoming fully integrated. A prospective observational 8-month study with 15 cross-sectional time points was performed to estimate the overall error index and mean error per drug use process stage. The error index is estimated by dividing the number of errors into error opportunities, and is expressed as a percentage. RESULTS: Computerized medical orders favored compliance with consensus protocols defined in software programs at the pharmacy department, even though the degree of adhesion degree was not quantitized. They also allowed a validation of all medical prescriptions by a pharmacist before dispensation. The total number of errors detected during the study period was 86. Error opportunities were 26,695, and the overall error index was 0.32%. During the study an error occurred every 312.5 error opportunities.