Background Selective serotonin reuptake inhibitors (SSRIs) may increase the risk ofmajor bleeding by decreasing platelet function or decreasing vitamin K antagonist(VKA) metabolism via cytochrome... Show moreBackground Selective serotonin reuptake inhibitors (SSRIs) may increase the risk ofmajor bleeding by decreasing platelet function or decreasing vitamin K antagonist(VKA) metabolism via cytochrome P450 (CYP) inhibition. Aims To determine whether SSRIs are associated with major bleeding during VKAtreatment and investigate the possible mechanisms. Methods In this cohort study, information on SSRI use and bleeding complicationswas obtained from patient records of VKAinitiators between 2006 and 2018 from twoanticoagulation clinics. Conditional logistic regression and time-dependent Cox re-gression were used to estimate the effect of SSRIs on a high international normalizedratio (INR >= 5) within 2 months after SSRI initiation and on major bleeding during theentire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9inhibitors. Results A total of 58,918 patients were included, of whom 1,504 were SSRI users.SSRI initiation versus nonuse was associated with a 2.41-fold (95% confidence interval[CI]: 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95% CI: 1.33-7.43)among CYP2C9-inhibiting SSRI users. The adjusted hazard ratio of major bleeding was1.22 (95% CI: 0.99-1.50) in all SSRI users and 1.31 (95% CI: 0.62-2.72) in CYP2C9-inhibiting SSRI users compared with nonusers. Conclusion SSRI use is associated with an increased risk of high INR and might beassociated with major bleeding. The risk of a high INR was slightly more elevated forCYP2C9-inhibiting SSRI users,suggesting theremight bea pharmacokineticinteraction(byCYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation Show less
Berger, F.A.; Weteringen, W. van; Sijs, H. van der; Hunfeld, N.G.M.; Bunge, J.J.H.; Groot, N.M.S. de; ... ; Gelder, T. van 2021
QTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in... Show moreQTc interval prolongation is an adverse effect associated with the use of fluoroquinolones and macrolides. Ciprofloxacin and erythromycin are both frequently prescribed QTc-prolonging drugs in critically ill patients. Critically ill patients may be more vulnerable to developing QTc prolongation, as several risk factors can be present at the same time. Therefore, it is important to know the QTc-prolonging potential of these drugs in the intensive care unit (ICU) population. The aim of this study was to assess the dynamics of the QTc interval over a 24-hour dose interval during intravenous ciprofloxacin and low-dose erythromycin treatment. Therefore, an observational study was performed in ICU patients (>= 18 years) receiving ciprofloxacin 400 mg t.i.d. or erythromycin 100 mg b.i.d. intravenously. Continuous ECG data were collected from 2 h before to 24 h after the first administration. QT-analyses were performed using high-end holter software. The effect was determined with a two-sample t-test for clustered data on all QTc values. A linear mixed model by maximum likelihood was applied, for which QTc values were assessed for the available time intervals and therapy. No evident effect over time on therapy with ciprofloxacin and erythromycin was observed on QTc time. There was no significant difference (p = 0.22) in QTc values between the ciprofloxacin group (mean 393 ms) and ciprofloxacin control group (mean 386 ms). The erythromycin group (mean 405 ms) and erythromycin control group (mean 404 ms) neither showed a significant difference (p = 0.80). In 0.6% of the registrations (1.138 out of 198.270 samples) the duration of the QTc interval was longer than 500 ms. The index groups showed slightly more recorded QTc intervals over 500 ms. To conclude, this study could not identify differences in the QTc interval between the treatments analyzed. Show less
Elens, L.; Langman, L.J.; Hesselink, D.A.; Bergan, S.; Moes, D.J.A.R.; Molinaro, M.; ... ; Lemaitre, F. 2020
Background: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none... Show moreBackground: COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals. Methods: This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature. Results: Management of drug-drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight. Conclusions: With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided. Show less
