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Aims: Pharmacovigilance signals of heart failure (HF) following exposure to protein kinase inhibitors (PKIs) have been detected in recent years. Our aim was to identify the PKIs most frequently associated with the development of HF. Methods: Using the French National Healthcare Database, all patients newly exposed to a PKI between January 2011 and June 2014 were followed up for 18 months. Specific hospitalization diagnosis and long-term HF-related disease codes were used to identify HF patients. HF incidence rate ratios (IRRs) were measured and adjusted hazard ratios (aHRs) were estimated using a Cox model. Sensitivity analyses were performed to limit the potential indication and competitive risk bias. Results: Thirteen PKIs were studied. Among the 49 714 new PKI users registered during the study period, the mean IRR of HF was 3.38 per 100 person-years, with a median time to onset of 155 days. We found a significant increase in the incidence of HF for six medicinal products: pazopanib (aHR = 2.42, 95% confidence interval [CI] 1.67-3.52), dasatinib (aHR = 2.22, 95% CI 1.42-3.44), ruxolitinib (aHR = 2.11, 95% CI 1.69-2.64), crizotinib (aHR = 1.71, 95% CI 1.07-2.72), everolimus (aHR = 1.45, 95% CI 1.26-1.67) and vemurafenib (aHR = 1.37, 95% CI 1.01-1.86). Sensitivity analyses were consistent with our primary analysis. Conclusions: The current study provides knowledge on HF following exposure to a PKI. Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two medicinal products with results slightly above the significance threshold, namely, crizotinib and vemurafenib, in our sensitivity analyses. [ABSTRACT FROM AUTHOR]

Concomitant nonsteroidal anti‐inflammatory drug (NSAIDs) and antithrombotic drug use is associated with an increased risk of bleeding, mainly gastrointestinal. The goal of this study was to quantify the transient increase in the risk of hospitalization for bleeding associated with NSAID use in patients treated with antiplatelet agents or anticoagulants. We performed a unidirectional case‐crossover study using the EGB (Échantillon généraliste de bénéficiaires), a permanent random sample of the French nationwide health database. Patients receiving antithrombotic therapy and hospitalized for bleeding between 2009 and 2017 were included. We compared their NSAID exposure during a 15‐day hazard window immediately before hospital admission to 3 earlier 15‐day control windows. The risk of hospitalization for bleeding associated with the recent use of NSAIDs was estimated using conditional logistic regression to estimate odds ratios (ORs). During the study period, 33 patients treated with anticoagulants and 253 treated with antiplatelet agents received NSAIDs and were included in the case‐crossover analysis. We found an increased risk of hospitalization for gastrointestinal bleeding after exposure to NSAIDs, with an adjusted OR of 3.59 (95%CI, 1.58‐8.17) in patients receiving anticoagulant therapy and 1.44 (95%CI, 1.07‐1.94) in patients receiving antiplatelet therapy. The risk of nongastrointestinal bleeding was also increased after exposure to NSAIDs with an adjusted OR of 2.72 (95%CI, 1.23‐6.04) in patients exposed to anticoagulant therapy. The risk of gastrointestinal and nongastrointestinal bleeding increases after NSAID use in patients treated with anticoagulants, while the risk of gastrointestinal bleeding increases, but to a lesser extent in those treated with antiplatelets. [ABSTRACT FROM AUTHOR]

Psychotropic drugs (PD) are often used close to a cancer diagnosis and may be considered as a way of coping. We aimed to determine the incidence of anxiolytics, hypnotics, antidepressants, and antipsychotics initiation around a diagnosis of chronic myelogenous leukemia (CML). Population‐based cohort: Data were extracted from Systeme National des données de Santé (SNDS, the French health insurance database) at the regional level (Midi‐Pyrenees area, 2.9 million inhabitants). All newly diagnosed patients treated by a CML tyrosine kinase inhibitor (TKI) between 10/01/2011 and 04/01/2014 were included. Pre‐CML (9 months before to 3 months before first TKI prescription—F‐TKI) and CML (3 months before to 9 months after F‐TKI) phases were defined. The main evaluation criterion was the initiation of PD during CML phase. Determinants associated with this incident PD use were studied through a logistic regression model. We compared pre‐CML and CML healthcare consumption. The cohort included 103 patients (mean age of 60.8 years). PD initiation rate was 35.9%, anxiolytics being the most initiated PD (59.5%). Advanced age was associated with PD initiation (adjusted OR = 1.029, 95% CI = 1.001–1.056). The number of consultations during the pre‐CML phase and female gender tended to be associated with increased risk of PD initiation in univariate analysis. For PD initiators, healthcare consumption was greater in CML but not in pre‐CML phase. PD initiation is a frequent finding around a CML diagnosis. Its risk increases with age. It could be a way to identify a subgroup with higher healthcare consumption. [ABSTRACT FROM AUTHOR]

Patients suffering from B‐cell non‐Hodgkin lymphomas (B‐NHL) have an increased likelihood of being exposed to proton pump inhibitors (PPIs), related to several factors which have been reported in the literature. PPIs are among the drugs most likely to be prescribed inappropriately. Consequently, B‐NHL patients could be particularly at risk of inappropriate PPI prescription, with potential adverse drug reactions. We aimed to evaluate the incidence of PPIs use and to identify factors associated with PPIs initiation during the active treatment phase of B‐NHL. We conducted a new‐user cohort study using regional data from the French national health insurance database in the Midi‐Pyrénées region (southwestern France). Incident B‐NHL patients were selected according to an algorithm of selection, validated with data from a cancer registry. Our study revealed that 48.9% (95% confidence interval [CI]: 45.2–52.6) of patients initiated PPIs during chemotherapy after B‐NHL diagnosis. According to information available in the SNDS, recommended indications for PPI prescriptions were identified in 21.1% of cases. Median duration of treatment was 65.3 days (CI: 35–112). Determinants of PPIs initiation were peptic ulcer disease, gastroprotection (appropriate or not) for medications considered at risk (NSAIDs, glucocorticoids and anticoagulants), age, nonfollicular lymphoma, polypharmacy, gastroenterologists' consultations and being hospitalized in a university hospital. Around 50% of patients initiated PPI treatment during the chemotherapy phase with only one‐fifth identified as appropriate prescriptions and with long durations of treatment in most cases. Given this background, appropriate PPI prescription should be promoted in B‐NHL to avoid potential inappropriate chronic use and related adverse events. [ABSTRACT FROM AUTHOR]

In adults, statins safety profile is well known. However, literature data on their adverse drug reactions (ADRs) remain scarce in children in real‐life setting. In order to better characterize ADRs related to 'real‐life' use of statins in children, we reviewed statin‐related ADRs recorded in the World Health Organization (WHO) global database of individual case safety reports (ICSRs), VigiBase. Methods. Individual case safety reports (ICSRs) in children (2–11 years) and adolescents (12–17 years) associated with statins from January 1, 1987, to July 18, 2017, were extracted from VigiBase. Characteristics of ICSRs, type of ADRs according to MedDRA classification (SOC and PT), and ICSR seriousness were described using SAS 9.4. A total of 311 ICSRs were identified for 8 statins with 712 ADRs. Musculoskeletal disorders (n = 85, 27.3%) were the first registered ADRs followed by general disorders (n = 67, 21.5%; mainly asthenia and pain). More than 1 out of 5 ADRs were 'injury, poisoning and procedural complications' (n = 67), mainly accidental or intentional exposures (n = 44, 14.1%), overdoses (n = 14, 4.5%), or off‐label use (n = 11, 3.5%). Overall, 133 (42.8%) reports were 'serious', including 11 deaths. Deaths mainly involved adolescents with intentional overdose and completed suicide with other associated drugs in 75% of reports. Our study identified rare but serious safety issues (rhabdomyolysis, myalgia, and hepatocellular injury). These ADRs can impact quality of life or lead to life‐threatening complications in children. Our results should be supplemented with other data sources. Spontaneous statin ADR reports in children to pharmacovigilance networks must be promoted. [ABSTRACT FROM AUTHOR]