Priscilla Karilline Do Vale Bezerra

Background: Hypomagnesemia, characterized by decreased levels of magnesium in the blood, is common among patients with cancer and may be related to the administration of proton pump inhibitors (PPIs) and/or platinum derivatives. Objective: To evaluate the safety and potential impact on serum magnesium levels of concomitant use of the PPI omeprazole in patients receiving a platinum derivative. Methods: This prospective, randomized, double-blind, single-dose, placebo-controlled study involved fixed doses of PPI administered on an outpatient basis. It spanned 4 cycles of platinum-based combination chemotherapy (21 days per cycle), and entailed a screening period (14 days before chemotherapy), 2 PPI treatment periods (total of 60 days), and a follow-up period (1 cycle). Patients recruited between May 2019 and March 2020 at 3 hospitals in Brazil were randomly assigned to receive placebo or PPI in a 1:1 ratio. Data analysis employed a linear mixed-effects model and Kaplan–Meier analysis. Results: A total of 164 patients were included in the study, 83 in the placebo group and 81 in the PPI group. Blood magnesium levels showed a modest decrease over time (by approximately 20%) across all patients. A correlation was observed between treatment duration and decrease in serum magnesium in the total sample (β = –0.035, 95% confidence interval [CI] –0.048 to –0.0021; p < 0.001). Compared with the placebo group, the PPI group showed a slightly greater decline (β = –0.121, 95% CI –0.231 to –0.011; p = 0.031). Additionally, no differences were noted between groups regarding the occurrence of neuropathy (p = 0.77), anorexia (p = 0.77), diarrhea (p = 0.34), or constipation (p = 0.39). Omeprazole use was associated with a lower incidence of nausea and vomiting (p = 0.005). Conclusion: These exploratory findings suggest that the concomitant use of omeprazole with platinum derivatives may be associated with a slightly faster rate of serum magnesium depletion than occurs with chemotherapy alone, but without clinical relevance or occurrence of frank hypomagnesemia. Keywords: magnesium, clinical oncology, platinum compounds, proton pump inhibitors, adverse effects Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2 RÉSUMÉ Contexte : L’hypomagnésémie se caractérise par une réduction des taux de magnésium dans le sang. Elle est répandue chez les patients atteints d’un cancer et peut être liée à l’administration d’inhibiteurs de la pompe à protons (IPP) et/ou de dérivés du platine. Objectif : Évaluer l’innocuité et l’incidence potentielle sur les taux sériques de magnésium de l’utilisation concomitante de l’IPP oméprazole chez des patients recevant un dérivé du platine. Méthodologie : Cette étude prospective, randomisée, à double insu, à dose unique et contrôlée par placebo portait sur des doses fixes d’IPP administrées en ambulatoire. Elle s’est déroulée pendant 4 cycles de chimiothérapie combinée à base de platine (21 jours par cycle) et comprenait une période de sélection (14 jours avant la chimiothérapie), deux périodes de traitement à l’IPP (comprenant 60 jours au total) et une période de suivi (1 cycle). Des patients recrutés dans 3 hôpitaux du Brésil entre mai 2019 et mars 2020 ont été répartis de manière aléatoire pour recevoir soit un placebo, soit un IPP, selon un ratio de 1:1. Un modèle linéaire à effets mixtes ainsi qu’une analyse de Kaplan-Meier ont été utilisés pour l’analyse des données. Résultats : Au total, 164 patients ont été inclus dans l’étude : 83 dans le groupe placebo et 81 dans le groupe IPP. Une diminution modeste avec le temps (environ 20 %) des taux sanguins de magnésium chez l’ensemble des patients a été constatée. Une corrélation a été observée entre la durée du traitement et la diminution du magnésium sérique chez l’ensemble des patients (β = –0,035; intervalle de confiance [IC] à 95 % : –0,048 à –0,002 1; p < 0,001). Cette diminution était légèrement plus marquée dans le groupe IPP que dans le groupe placebo (β = –0,121; IC à 95 % : –0,231 à –0,011; p = 0,031). De plus, aucune différence n’a été observée entre les groupes concernant la survenuede neuropathie (p = 0,77), d’anorexie (p = 0,77), de diarrhée (p = 0,34) ou de constipation p = 0,39). L’utilisation de l’oméprazole était associée à une incidence plus faible de nausées et de vomissements (p = 0,005). Conclusion : Ces résultats exploratoires indiquent que l’utilisation concomitante de l’oméprazole avec des dérivés du platine pourrait être associée à une diminution légèrement plus rapide des taux sériques de magnésiumque celle observée avec la chimiothérapie seule, sans toutefois présenter de pertinence clinique ni entraîner la survenue d’une hypomagnésémie franche. Mots-clés : magnésium, oncologie clinique, composés du platine, inhibiteurs de la pompe à protons, effets indésirables Inscription à l’essai clinique : Brazilian Registry of Clinical Trials (ReBEC) RBR-8vsb7k2

Objectives: To evaluate the impact on clinical parameters and maternal-foetal outcomes of serious drug interactions in high-risk hospitalized pregnant women. Methods: A prospective cohort study including 571 pregnant women hospitalized between September 2019 and June 2022, with an average age of 30.6 years, mostly diagnosed with hypertensive syndromes (69.7%) and gestational diabetes (57.1%). Drug interactions were characterized daily through Lexicomp®, with monitoring of clinical parameters linked to their mechanisms of action. We used a multivariable logistic regression model with demographic and treatment variables to identify factors associated with drug interactions. In a second model, we analysed the impact of serious drug interactions on clinical outcomes, including maternal-foetal outcomes such as macrosomia, foetal tachycardia, amniotic fluid abnormalities, and prematurity. Key findings: We identified 203 pregnant women with one or more serious drug interactions (35.6%), and the risk factors were gestational age (adjusted odds ratio [AOR]: 0.96; 95% CI: 0.93–0.98), diagnosis of hypertension (AOR: 3.00; 95% CI: 2.49–6.41), number of medications (AOR: 1.09; 95% CI: 1.03–1.15), and length of hospitalization (AOR: 1.18; 95% CI: 1.12–1.26). Dipyrone and acetylsalicylic acid co-administration increased systolic blood pressure (AOR: 2.12; 95% CI: 1.01–4.47), while scopolamine and levomepromazine resulted in greater drowsiness (AOR: 5.38; 95% CI: 1.66–17.40) and a temperature increase (AOR: 5.96; 95% CI: 1.23–28.98). Conclusion: High-risk pregnant women of lower gestational age or with hypertensive syndromes are exposed to severe drug interactions, yet these interactions show limited clinical impact and do not significantly affect maternal-foetal outcomes.

To characterize severe potential drug interactions in maternal intensive care, and to determine their frequency, risk factors and potential risk medications. An observational and longitudinal study conducted between December 2014 and December 2015 in a maternal intensive care unit. Clinical data were collected and severe potential drug interactions were identified on pregnant inpatients. The drug interactions were classified by type, prevalence and exposure rate. A multivariate logistic regression model was used to identify the severe potential drug interactions and the related drugs (p<0.05). A total of 95.1% of patients were exposed to, at least, one potential drug interaction; in that, 91.7% 33.9% were related to, respectively, moderate and severe potential drug interactions. The patients were exposed, on average, on 69.2% of days they were in the intensive care unit. The main drugs involved in more severe drug interactions were magnesium sulfate, metoclopramide, propranolol and diazepam. The severe potential drug interactions were observed in almost all patients of the study, and, approximately one third of those interactions were related to greater severity and resulted in exposure during long hospital stay. The higher number of prescribed drugs and its previous use of medications at home increase the occurrence of severe potential drug interactions.