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Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase^®.

ABSTRACT: We aimed to perform an analysis of individual case safety reports retrieved after the Standardized MedDRA Query "Pregnancy and neonatal topics" for which Direct-Acting Oral Anticoagulants (DOACs) were claimed as suspected/interacting drugs. Additionally, to investigate if exists a disproportion of cases reporting "Pregnancy and neonatal topics" adverse events rather than other adverse events for DOACs in comparison with all other drugs registered in VigiBase or warfarin. VigiBase, the World Health Organization (WHO)'s global database of individual case safety reports was used as data source. Forty-two cases of abortion were detected of which 18 (42.8%) had alternative causes for its occurrence. Fourteen cases reported congenital anomaly (8 cases) or low birth weight baby/fetal growth restriction (6 cases) of which 62.5% and 33.3% had at least one confounder, respectively. In the disproportionality analyses, a potential safety signal for spontaneous abortion emerged for rivaroxaban (Reporting Odds Ratio, ROR 2.70; 95% CI 1.79-4.07) and apixaban (ROR 6.76; 95% CI 2.99-15.25). However, when the same analyses were performed using only cases without alternative causes, no statistically significant associations for rivaroxaban when compared to all other drugs (ROR 1.05; 95% CI 0.54-2.02) or warfarin (ROR 0.79; 95% CI 0.47-1.32) were found. For apixaban, we found a statistically significant ROR for induced abortion when compared to all other drugs or warfarin. For the majority of cases claiming DOACs-induced teratogenic effects, spontaneous or induced abortion there was at least one alternative cause explaining the occurrence of the adverse events. For rivaroxaban, when cases without confounders were considered, no safety signals emerged. However, for apixaban, we found a potential safety signal suggesting an increased probability of reporting spontaneous/induced abortion rather than other events when compared to all other drugs or warfarin.

SUBMITTER: Sessa M

PROVIDER: S-EPMC6510783 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase<sup>®</sup>.

Sessa Maurizio M Mascolo Annamaria A Callréus Torbjörn T Capuano Annalisa A Rossi Francesco F Andersen Morten M

Scientific reports 20190510 1

We aimed to perform an analysis of individual case safety reports retrieved after the Standardized MedDRA Query "Pregnancy and neonatal topics" for which Direct-Acting Oral Anticoagulants (DOACs) were claimed as suspected/interacting drugs. Additionally, to investigate if exists a disproportion of cases reporting "Pregnancy and neonatal topics" adverse events rather than other adverse events for DOACs in comparison with all other drugs registered in VigiBase or warfarin. VigiBase, the World Heal ...[more]

PMID: 31076635

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Project description:Background & aimsUse of direct-acting oral anticoagulants (DOACs) is increasing, but little is known about the associated risks in patients undergoing colonoscopy with polypectomy. We aimed to determine the risk of post-polypectomy complications in patients prescribed DOACs.MethodsWe performed a retrospective analysis using Optum's de-identified Clinformatics Data Mart Database (2003-2016) (a de-identified administrative database from a large national insurance provider) to identify adults who underwent colonoscopy with polypectomy or endoscopic mucosal resection (EMR) from January 1, 2011, through December 31, 2015. We collected data from 11,504 patients prescribed antithrombotic agents (1590 DOAC, 3471 warfarin, and 6443 clopidogrel) and 599,983 patients not prescribed antithrombotics of interest (controls). We compared 30-day post-polypectomy complications, including gastrointestinal bleeding (GIB), cerebrovascular accident (CVA), myocardial infarction (MI), and hospital admissions, of patients prescribed DOACs, warfarin, or clopidogrel vs controls.ResultsPost-polypectomy complications were uncommon but occurred in a significantly higher proportion of patients receiving any antithrombotic vs controls (P < .001). The percentage of patients in the DOAC group with GIB was 0.63% (95% CI, 0.3%-1.2%) vs 0.2% (95% CI, 0.2%-0.3%) in controls. The percentage of patients with CVA in the DOAC group was 0.06% (95% CI, 0.01%-0.35%) vs 0.04% (95% CI, 0.04%-0.05%) in controls. After we adjusted for bridge anticoagulation, EMR, Charlson comorbidity index (CCI), and CHADS2 (congestive heart failure, hypertension, age over 75, diabetes, stroke [double weight]) score, patients prescribed DOACs no longer had a statistically significant increase in the odds of GIB (odds ratio [OR], 0.90; 95% CI, 0.44-1.85), CVA (OR, 0.45; 95% CI, 0.06-3.28), MI (OR, 1.07; 95% CI, 0.14-7.72), or hospital admission (OR, 0.86; 95% CI, 0.64-1.16). Clopidogrel, warfarin, bridge anticoagulation, higher CHADS2, CCI, and EMR were associated with increased odds of complications.ConclusionIn our retrospective analysis of a large national dataset, we found that patients prescribed DOACs did not have significantly increased adjusted odds of post-polypectomy GIB, MI, CVA, or hospital admission. Bridge anticoagulation, higher CHADS2 score, CCI, and EMR were risk factors for GIB, MI, CVA, and hospital admissions. Studies are needed to determine the optimal peri-procedural dose for high-risk patients.

Project description:Introduction: Clozapine is primarily reserved for treatment-resistant schizophrenia due to safety concerns associated with its use. Infections have been reported with clozapine, which may lead to elevated serum levels of the drug. However, the existing literature on this topic is limited. Therefore, we conducted a study using VigiBase® to investigate the potential over-reporting of infections associated with clozapine, to explore the presence of dose-dependency, and to investigate the underlying mechanism. Methods: Disproportionality analyses were performed using VigiBase to assess the association between clozapine and all types of infections, the association between clozapine-associated infections and neutropenia, the association between clozapine-associated infections and agranulocytosis, the dose-effect relationship between clozapine and infections, and the interaction between clozapine and the main strong CYP450 inhibitors using reports carried out until 11 April 2023. Results: A statistically significant signal of infections was observed with clozapine, as indicated by an information component of 0.43 [95% CI: (0.41-0.45)]. The most commonly reported infections were respiratory and gastrointestinal in nature. Neutropenia showed weaker association with clozapine-associated reports of infections compared to other clozapine-associated reports [X2 (1, N = 204,073) = 454; p < 0.005], while agranulocytosis demonstrated a stronger association with clozapine-associated reports of infections [X2 (1, N = 204,073) = 56; p < 0.005]. No evidence of dose-dependency was observed. Among the 17 tested CYP inhibitors, significant drug-drug interactions were found with clarithromycin, metronidazole, valproic acid, lansoprazole, omeprazole, amiodarone, and esomeprazole. Discussion: Our study revealed a significant safety signal between clozapine use and infections, predominantly respiratory and gastrointestinal infections. The co-administration of clozapine with valproic acid or proton pump inhibitors may potentially contribute to an increased risk of infection. Further vigilance is warranted in clinical practice, and consideration of therapeutic drug monitoring of clozapine in cases involving concomitant use of these drugs or in the presence of infections may be beneficial.

Project description:IntroductionThe Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS).ObjectiveSignals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA).MethodsSDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase®). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models.ResultsThe median overlap between EVDAS and FAERS or VigiBase® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase®. Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy.ConclusionsOrganizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.

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Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase^®.

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Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase<sup>®</sup>.

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Dataset Information

Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase®.

Publications

Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase<sup>®</sup>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Direct-acting oral anticoagulants (DOACs) in pregnancy: new insight from VigiBase^®.