Objectives To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine. Design Prescription-event monitoring studies. Setting Prescriptions were obtained for each cohort in the immediate post-marketing period. Subjects Event data were obtained for a total of 43 363 patients. Main outcome measure Reporting of sedation or drowsiness. Results The odds ratios (adjusted for age and sex) for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P = 0

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This study found no evidence of an increased risk of suicidal ideation during treatment with atomoxetine, compared to the period prior to starting treatment. Amongst age specific subgroups, this risk may change. Nonetheless, individual case assessment suggested a causal relationship in some patients, hence physicians need to be aware of the possibility of developing this event, and furthermore consider how best to detect it in this paediatric population. This study demonstrates the importance of combining quantitative statistical analyses with a qualitative case series assessment.

This study has shown that the treatment with pioglitazone was associated with a low incidence of hypoglycaemia. The factors possibly increasing the risk of hypoglycaemia were concomitant therapy with sulfonylurea or insulin and female gender.

Oral non-steroidal anti-inflammatory drugs (NSAIDs) are known to be associated with an increased risk of bleeding. The NSAID, flurbiprofen, in the form of 8.75 mg lozenge or oromucosal spray is indicated for the symptomatic relief of sore throat. Despite the low dose as compared to alternative flurbiprofen preparations, concerns have been raised regarding its safety in terms of haemorrhagic events. This systematic review was conducted to identify existing evidence on the risk of haemorrhagic events with flurbiprofen 8.75 mg dose (any formulation), particularly where this may be due to potential interactions with other medicinal products. The systematic review examined studies reporting haemorrhagic events in patients receiving flurbiprofen 8.75 mg dose. Six individual electronic databases were searched up to 28th April 2020. Records were initially screened for relevance followed by further review of potentially eligible studies. Data extraction was performed for eligible studies and risk of bias in studies was assessed. The search strategy identified 1093 individual records. Of these, 1038 records were excluded after initial review; the majority of these records related to flurbiprofen in alternative formulations with alternative doses (e.g., eye drops, skin patches, oral tablets) thus were not considered relevant for further review. The 55 remaining records related to flurbiprofen 8.75 mg dose (any formulation) or flurbiprofen lozenge/oromucosal spray where the dose was not specified. After further review, 52 of these records were not considered eligible. Thus, only three records were included in this systematic review. The three studies reported a total of five haemorrhagic events in patients taking flurbiprofen 8.75 mg lozenge; the corresponding risk in each of the studies was 8.33, 1.98 and 1.96%. Where possible, comparison of flurbiprofen 8.75 mg lozenge to placebo produced risk ratios of 0.96 (95% CI 0.07, 13.25) and 2.00 (95% CI 0.10, 118.0). This systematic review found limited evidence on the risk of haemorrhagic events with flurbiprofen when used at a dose of 8.75 mg. Counts were low across all studies and results comparing flurbiprofen and placebo treatment arms were non-significant. However, scarcity of studies and low certainty of evidence for the outcome of haemorrhagic events limits the conclusions of this systematic review.

Introduction Although the direct oral anticoagulant rivaroxaban is recommended for stroke prevention in patients with non-valvular atrial fibrillation based on Phase III clinical trials, there is still a need for additional safety data from everyday clinical practice. The ROSE study was initiated to collect further information on the safety and utilisation of rivaroxaban in a broader range of patient groups in routine clinical practice. Methods and results The ROSE study was conducted in hospitals in England and Wales. Consenting adults with non-valvular atrial fibrillation newly started on rivaroxaban were eligible and followed up for 12 weeks. Data was derived through secondary use of medical records. The primary outcome was major bleeding within gastrointestinal, urogenital and intracranial sites. A total of 4846 patients were enrolled in the study September 2013 to January 2016, 965 of which were treated with rivaroxaban for non-valvular atrial fibrillation. The median age in the rivaroxaban non-valvular atrial fibrillation cohort was 76 years, 53.6% were male. The median HAS-BLED score was 2 and the median CHA 2 DS 2-VASc score was 4. The risk of major bleeding within each of the primary sites of gastrointestinal, urogenital and intracranial during the 12 week observation period was low (0.2%; n = 2). The risk of major bleeding in all sites was 1.0% (n = 10) at a rate of 5.5 events per 100 patient years. Conclusion In terms of the primary outcome risk of major bleeding within gastrointestinal, urogenital and intracranial sites during the 12 week observation period, the risk estimates in the non

This study demonstrated that modified SDMs can be used to detect differences in the AE profiles between children and adults taking a medicinal product, and also to identify drug safety signals.

Objective To review the results of non-interventional observational cohort studies of 14 772 patients treated with ®nasteride and 12 484 patients treated with tamsulosin, both studies being of national proportions and undertaken in general medical practice in England. Methods Both studies were undertaken by prescriptionevent monitoring (PEM), whereby the exposure data are derived from information provided in strict con®dence by the Prescription Pricing Authority of the National Health Service. The outcome data are derived from`green form' questionnaires completed by the prescribing general practitioners (GPs). Additional data are obtained by medical follow-up with the attending practitioners. Adverse experience was measured in three ways; as reports of events which the doctors considered to represent adverse drug reactions; as reports of reasons for stopping the drug; and by studying the incidence density of each reported event. For these purposes a computerized dictionary containing 1430 higher level terms was used. The duration of exposure in the ®nasteride study was < 1 year and was < 6 months in the tamsulosin study. Results The outcome data on the 14 772 and 12 484 patients treated in the ®nasteride and tamsulosin studies were derived from the 63% and 57.4% of the green forms sent out and returned, respectively. The ®nasteride cohort included two women and the tamsulosin cohort 70 women. The mean (SD) age of the men in the two cohorts was, respectively, 69.0 (9.2) and 66.2 (11.7) years. Both drugs were well tolerated on long-term therapy and 69.6% (10 274 patients) of the total ®nasteride and 62.0% (7739 patients) of the total tamsulosin cohort were still receiving the drug at the end of 6 months. In the ®nasteride study, impotence or ejaculatory failure was reported in 2.0% of the patients still receiving the drug; there were reports of decreased libido in 1.0% and gynaecomastia was reported whilst the drug was still being prescribed in 39 patients (0.3% of the cohort). With tamsulosin, uncommon cases of dizziness, headache, malaise and hypotension (89 reports in 12 484 patients, i.e. 0.7% of the cohort) were common to the ®ndings of reported adverse reactions, reasons for stopping the drug and events of highest incidence density. None of the deaths which occurred in either of these large cohorts was attributed by either the reporting GPs or the PEM medical staff to the drugs examined. Conclusion The GPs rated the drugs effective in most patients; tolerance and adverse experience was consistent with the known pharmacology of the two drugs. No serious, unexpected adverse effects were identi®ed.