Portuguese Pharmacovigilance System Research Articles

Hepatotoxicity Related to Agomelatine and Other New Antidepressants

Antidepressants have been associated with a low incidence of idiosyncratic hepatic injury. Some of them, nefazodone or amineptine, were observed to induce severe hepatic injury and withdrawn from the market. Recently, some cases of this severe condition have been reported in association with agomelatine use. Therefore, the objective of this study is to learn the risk of hepatic damage with agomelatine as compared with other new antidepressants. We took data from the Spanish, French, Italian, and Portuguese pharmacovigilance system databases. A case/noncase approach to assess the strength of the association between whichever antidepressant and hepatotoxicity was performed; cases were defined as reports of hepatotoxicity; noncases were reports of all reactions other than hepatotoxicity. Exposure was the recording of a new antidepressant in a report, whether or not it was suspected of causing the reaction. During the period surveyed, 3300 cases of hepatotoxicity were collected for the antidepressants assessed. They represent 10.3% of all cases collected for these drugs; the corresponding figure for all drugs was 6.0%. Meanwhile, 63 cases of hepatotoxicity associated with agomelatine were collected since its introduction until the end of the period studied; they account for a percentage of 14.6. Agomelatine was statistically associated with hepatotoxicity in Spain [reporting odds ratio (ROR), 4.9 (95% confidence interval [CI], 2.4-9.7)], France (ROR, 2.4 [95% CI, 1.5-3.7]), and Italy (ROR, 5.1 [95% CI, 1.7-14.0]). Current results support the idea of agomelatine to be related to a higher hepatotoxicity risk. Physicians should consider early discontinuation if the condition is suspected; health authorities should promptly explore the best regulatory actions to be taken.

Safety profiles of adalimumab, etanercept and infliximab: a pharmacovigilance study using a measure of disproportionality in a database of spontaneously reported adverse events

Despite being effective, the biologics approved for treating rheumatoid arthritis have been associated with serious adverse events. This study is aimed at comparing the safety profiles of adalimumab, etanercept and infliximab by analysing the disproportionalities of the associations between the different adverse events and the different biologics in the Portuguese spontaneous reporting database. Adverse events spontaneously reported to the Portuguese pharmacovigilance system (PPS) between 2009 and 2011 were included. Adverse events were classified according to MedDRA in the primary system organ class. The reporting odds ratio (ROR) and its 95% confidence intervals (CI) were calculated for each biologic regarding the various categories of adverse events. Microsoft Excel was used to perform all the calculations. The PPS received 12167 adverse events reported for all drugs, of which 741 were reported for biologics: 157 for adalimumab, 132 for etanercept and 452 for infliximab. Compared with the all other drugs, adalimumab, etanercept and infliximab were all disproportionately associated with 'infections and infestations' (ROR: 6·65, 95% CI: 4·50-9·83; ROR: 2·74, 95% CI: 1·56-4·81; ROR: 2·95, CI 95%: 2·16-4·02, respectively) and with 'neoplasms benign, malignant and unspecified' (ROR: 7·23, 95% CI: 3·92-13·33; ROR: 6·26, 95% IC: 3·12-12·57; ROR: 3·94, 95% CI: 2·41-6·44, respectively), etanercept with 'general disorders and administration site conditions' (ROR: 2·08, 95% CI: 1·44-3·02) and infliximab with 'immune system disorders' (ROR: 5·17, 95% CI: 3·50-7·64), 'respiratory, thoracic and mediastinal disorders' (ROR: 1·80, 95% CI: 1·31-2·48) and 'investigations' (ROR: 1·82, 95% CI: 1·19-2·78). When interpreting the results one should take into consideration the number of patients exposed and should not only rely on the number of adverse events reported. Although the disproportionalities found for adalimumab and etanercept may suggest strong associations with particular adverse events, caution is needed when drawing conclusions on the association between infliximab and the adverse events analysed. In the light of the present findings, these results deserve further evaluation.

PS-024 Monitoring of adverse drug reactions in patients treated with new oral anticoagulants

BackgroundData on the adverse effects of newly marketed drugs are limited. The monitoring of adverse drug reactions (ADR) through active pharmacovigilance is vital to patient safety.The new oral anticoagulants dabigatran...

Drug-induced anaphylaxis: a decade review of reporting to the Portuguese Pharmacovigilance Authority

Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance authority during the past decade. Patients' demographic data and implicated drugs were analyzed as well as the severity of the ADR and time trends. This study was a retrospective analysis of episodes of anaphylaxis, defined according to the Second Symposium on the Definition and Management of Anaphylaxis Criteria, reported to the Portuguese Pharmacovigilance System between 1 January 2000 and 1 November 2010 Amongst the 16,157 ADR reported to the Portuguese Pharmacovigilance System during the 10-year study period, we found 918 (6 %) cases of anaphylaxis that met the proposed criteria. The age of the patients varied from 7 days to 91 years, with 87 cases (9 %) of anaphylaxis involving patients under 18 years of age. There was an overall female predominance (67 %), but the majority of pediatric patients were male (56 %). There was a trend toward increased reporting as the decade progressed, and 31 % (284) of all anaphylaxis cases were reported during the last 2 years of the study period. Of the anaphylaxis episodes reported, 19 % led to hospitalization and 24 (3 %) had a fatal outcome. Antibiotics were responsible for most cases (17 %) followed by nonsteroidal anti-inflammatory drugs/acetaminophen (13 %), antineoplastic/cytotoxic drugs and immune-modulators. Vaccines and radiographic contrast media were also important contributors to an anaphylactic event. In this series of drug-related anaphylaxis, we found that most of the reported episodes were associated with widely used drugs, such as antibiotics and analgesics. Anaphylaxis can occur at any age. The female gender was more highly represented, with the exception of pediatric patients.