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WhatIs Known and Objective. Anti‐EGFR (epidermal growth factor receptor) drugs are indicated for non‐small‐cell lung cancer (NSCLC). This review summarises the information available to date on the first anti‐EGFRs granted market authorisation: erlotinib TARCEVA®, gefitinib IRESSA®, afatinib GIOTRIF®, dacomitinib VIZIMPRO®, and osimertinib TAGRISSO®. Methods. A literature search was conducted in the PubMed database including studies published in English using the terms gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Furthermore, bibliographies of selected references were also studied for relevant articles. Clinical trial (CT) data were extracted from clinicaltrials.gov (ongoing trials and adverse events (AEs)). Assessment of AEs for these drugs was conducted using global pharmacovigilance data from VigiBase®. Results and Discussion. Erlotinib and gefitinib are first‐generation anti‐EGFR drugs, able to bind competitively and reversibly to the ATP‐ (adenosine triphosphate‐) binding site of the EGFR exon 19 and exon 21 mutations. Afatinib and dacomitinib are second‐generation anti‐EGFRs able to bind covalently and irreversibly to the ATP site and inhibit EGFR and HER (human epidermal growth factor receptor) such as HER2 and HER4 enzyme activity. Osimertinib is a third‐generation PKI and overcomes the EGFR T790M gatekeeper mutation through covalent binding at the ATP site. Medical interactions with these drugs are reported, notably with cytochrome P450 inducers or inhibitors. The most reported AEs in CTs are cutaneous reactions and gastrointestinal disorders. The occurrence of cutaneous reactions is less reported with third generation than with first‐ and second‐generation anti‐EGFR drugs. These results are consistent with the results from the VigiBase® global pharmacovigilance database. What Is New and Conclusion. This review summarises current knowledge regarding five anti‐EGFRs in the literature. The third‐generation anti‐EGFR appears to be more effective than the first and second generations and is indicated as first‐line therapy. This trial is registered with NCT01523587, NCT01466660, NCT01774721, NCT01360554, and NCT02296125. [ABSTRACT FROM AUTHOR]

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]

Introduction: Fluoroquinolones are widely used to treat bacterial infections. Many in vitro and in vivo studies have established a chemical relationship between fluoroquinolones' particular chemical structure and photosensitivity. The aim of this study was to establish a relationship between the chemical structure of fluoroquinolones and the risk of photosensitivity adverse effects from real-world data.Methods: All the Individual Case Safety Reports (ICSRs) related to fluoroquinolones and registered in the World Health Organization global database (VigiBase®) up to December 31, 2017 were collected. A disproportionality analysis was performed in order to quantify the photosensitivity risk for each fluoroquinolone by calculating their reporting odds ratio (ROR).Results: Up to December 31, 2017, 282,805 ICSRs related to fluoroquinolones were selected, of which 1647 were photosensitivity adverse event cases. Sparfloxacin had the highest adjusted ROR of 161.10 (95% confidence interval [CI] 133.66-194.02) followed by grepafloxacin (40.30 [26.30-59.60]) closely followed by lomefloxacin (32.61 [28.61-37.07]), then enoxacin (11.04 [8.33-14.32]) and fleroxacin (8.22 [5.06-12.56]).Conclusion: This study confirms the high reporting rate of photosensitivity adverse effects for sparfloxacin from real-world data. Moreover, our data suggest more photosensitivity adverse effects reporting for fluoroquinolones with a halogen at their 8th position. [ABSTRACT FROM AUTHOR]