OBJECTIVETo analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications.RESEARCH DESIGN AND METHODSCase/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR).RESULTSNinety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82–6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively).CONCLUSIONSIn agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.

In patients with diabetes, disease per se, co-morbidities and drugs, including novel agents acting on the incretin system, have all been associated with pancreatitis with controversial data. We investigated the publicly available FDA Adverse Event Reporting System (FDA_AERS) database to gain insight into the possible association between antidiabetic agents and pancreatitis. To this aim, a case/non-case method was retrospectively performed on the FDA_AERS database (2004-2009 period). Cases were defined as reports of pancreatitis according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. All other reports associated with antidiabetics were considered non-cases. The Reporting Odds Ratio (RORs), with corresponding 95% confidential interval (CI) and Mantel-Haenszel corrected P value, was calculated as a measure of disproportionality, with subsequent time-trend analysis. We retrieved 86,938 reports related to antidiabetics, corresponding to 159,226 drug-report combinations: 2,625 cases and 156,601 non-cases. Disproportionality was found only for exenatide (number of cases, 709; ROR, 1.76; 95% CI, 1.61-1.92; P MH < 0.001) and sitagliptin (128; 1.86; 1.54-2.24; <0.001). For exenatide, significant disproportionality appeared in the first quarter of 2008 (ROR, 1.24; 95% CI, 1.10-1.40; P MH < 0.001), soon after the FDA alert; for sitagliptin in the second quarter of 2008 (1.41; 1.05-1.90; 0.021). This temporal analysis found a striking influence of relevant FDA warnings on reporting of pancreatitis (the so-called notoriety bias) and is, therefore, recommended to avoid transforming a pharmacovigilance signal of alert automatically into an alarm. The precise quantification of the risk of pancreatitis associated with antidiabetics deserves assessment through specific disease-based registries.

To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

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Aims The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically‐important drug–drug interactions (DDIs) in poly‐treated elderly patients. Methods We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly‐treated (≥four drugs) elderly (>65 years) patients in the Emilia Romagna region during January 2011–June 2011 (first pre‐intervention period), January 2012–June 2012 (second pre‐intervention period) and January 2013–June 2013 (post‐intervention period). Educational initiatives to GPs were completed in July 2012–December 2012. Pre‐test/post‐test analysis (2013 vs. 2012) was performed, also using predicted 2013 data (P < 0.01 for statistical significance). Results Despite the slight increase in poly‐therapy rate (16% in 2013, +1.5% from 2011), we found a stable or slightly declining number of potential DDIs for each elderly poly‐treated patient (~1.5). In 2013, 11 DDIs exceeded 5% of prevalence rate: antidiabetics‐β‐adrenoceptor blockers ranked first (20.3%), followed by ACE Inhibitors (ACEIs)/sartans‐non steroidal anti‐inflammatory drugs (NSAIDs) (16.4%), diuretics‐NSAIDs (13.6%), selective serotonin re‐uptake inhibitors (SSRIs)‐NSAIDs/acetyl salicylic acid (ASA) (12.7%) and corticosteroids‐NSAIDs/ASA (9.7%). A remarkable reduction emerged for NSAID‐related DDIs (diuretics‐NSAIDs peaked −14.5%; P < 0.01), whereas prevalence of antidiabetics‐β‐adrenoceptor blockers increased (+7.9%; P < 0.01). When using predicted values, the statistical significance disappeared for antidiabetics‐β‐adrenoceptor blockers (+1.3%; P = 0.04), whereas it persisted for almost all NSAIDs‐related DDIs: ACEIs/sartans‐NSAIDs (−3.0%), diuretics‐NSAIDs (−6.0%), SSRIs‐NSAIDs/ASA (−5.9%). Conclusions This campaign contained the burden of DDIs in poly‐treated elderly patients by 1) reducing most prevalent DDIs, especially NSAIDs‐related DDIs and 2) balancing the observed rise in poly‐therapy rate with stable rate in overall prescriptions of potentially interacting drugs per patient.