[Show abstract][Hide abstract] ABSTRACT: Use of food supplements-containing phytoestrogens among postmenopausal women is rapidly increasing. Although phytoestrogens are often perceived as safe, evidence for overall positive risk-benefit profile is still inconclusive. The chance to buy them by user's initiative does not facilitate surveys on their prevalence and pattern of use. The aim of this study was to describe the pattern of use and self-reported positive and negative perceptions of phytoestrogens in post-menopausa.
BMC Complementary and Alternative Medicine 07/2014; 14(1):262. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Phytoestrogens represent a diverse group of non-steroidal natural products, which seem to have some oestrogenic effects and are often marketed as food supplements. Population exposed to phytoestrogens is potentially increasing, in part because an unfavourable risk-benefit profile of Hormone Replacement Therapy (HRT) for prolonged treatments (e.g., osteoporosis prevention) highlighted by the publication of the Women Health Initiative (WHI) trial in 2002, also in part because many post-menopausal women often perceived phytoestrogens in food supplements as a safer alternative than HRT. Despite of increasing preclinical and clinical studies in the past decade, appealing evidence is still lacking to support the overall positive risk-benefit profile of phytoestrogens. The status of phytoestrogens as food supplements seem discourage studies to obtain new evidence, and the chance to buy them by user's initiative make it difficult to survey on their prevalence and pattern of use. The aim of the present review is to: (a) outline the clinical scenario underlying the increase interest on phytoestrogens, by overviewing the evolution of the evidence on HRT and its main therapeutic goals (e.g., menopausal symptoms relief, chemoprevention, osteoporosis prevention); (b) address the chemical and pharmacological features (e.g. chemical structure, botanical sources, mechanism of action) of the main compounds (e.g., isoflavones, lignans, coumestans); (c) describe the clinical evidence on potential therapeutic applications; (d) put available evidence on their risk-benefit profile in a regulatory perspective, in light of the recent regulation on health claims of food supplements.
Current Medicinal Chemistry 10/2013; · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this article is to investigate the vascular safety profile of triptans through an analysis of the United States Food and Drug Administration Adverse Event Reporting System (FDA_AERS) database with a special focus on serious and unexpected adverse events.
A CASE/NON-CASE analysis was performed on the reports entered in the FDA_AERS from 2004 to 2010: CASES were reports with at least one event included in the MedDRA system organ classes 'Cardiac disorder' or 'Vascular disorders', whereas NON-CASES were all the remaining reports. Co-reported cardiovascular drugs were used as a proxy of cardiovascular risk and the adjusted reporting odds ratio (adj.ROR) with 95% confidence intervals (95% CI) was calculated. Disproportionality signals were defined as adj.ROR value >1. Adverse events were considered unexpected if not mentioned on the relevant label.
Among 2,131,688 reports, 7808 concerned triptans. CASES were 2593 among triptans and 665,940 for all other drugs. Unexpected disproportionality signals were found in the following high-level terms of the MedDRA hierarchy: 'Cerebrovascular and spinal necrosis and vascular insufficiency' (103 triptan cases), 'Aneurysms and dissections non-site specific' (15), 'Pregnancy-associated hypertension' (10), 'Reproductive system necrosis and vascular insufficiency' (3).
Our analysis revealed three main groups of unexpected associations between triptans and serious vascular events: ischaemic cerebrovascular events, aneurysms and artery dissections, and pregnancy-related vascular events. A case-by-case assessment is needed to confirm or disprove their plausibility and large-scale analytical studies should be planned for risk rate estimation. In the meantime, clinicians should pay special attention to migraine diagnosis and vascular risk assessment before prescribing a triptan, also promptly reporting any unexpected event to pharmacovigilance systems.
[Show abstract][Hide abstract] ABSTRACT: To describe antidepressant (AD) use in the Emilia-Romagna Region (Italy) and to evaluate adherence to treatment with selective serotonin receptor inhibitors or selective noradrenaline receptor inhibitors (SSRI-SNRI).
Reimbursed prescriptions of AD were retrieved from the Emilia-Romagna Regional Health Authority Database. The overall AD consumption from the 2006-2011 period was expressed in terms of prevalence and amount of use. Adherence to treatment was assessed in a cohort of patients who received SSRI-SNRI, and was followed throughout a 6-month period from the start of each treatment episode. Adherence was considered according to three parameters: duration of treatment ≥ 120 days, prescription coverage ≥ 80 %, and gaps between prescriptions < 3 months. Determinants of non-adherent regimen, including sociodemographic and clinical variables, were identified by multivariate logistic regression by calculating adjusted Odds Ratio (adjOR) and the relevant 95 % confidence interval (95CI).
From 2006 to 2011, the prevalence of use of AD increased by 5 % (from 86 to 90 per 1,000 inhabitants) and the amount of antidepressant consumption increased by 20 % (from 43 to 51 defined daily dose per thousand inhabitants per day [DDD/TID]), with a 14 % rise in the intensity of drug use (from 182 to 208 DDD per patient). Out of 347,615 SSRI-SNRI treatment episodes, only 23.8 % were adherent. Comorbidity (adjOR:0.69; 95CI:0.67-0.72) and recurrence of AD treatment in the previous year (0.91; 0.89-0.92) were associated with better adherence. Moreover, patients treated with duloxetine (0.58; 0.55-0.60), escitalopram (0.64; 0.62-0.66) or sertraline (0.65; 0.64-0.67) showed better adherence in comparison with paroxetine.
Clinical variables resulting in improved adherence seem to identify patients with more severe disorders and who actually need a pharmacological approach, whereas differences in adherence among ADs could in part be caused by channeling and sponsorship bias. Initiatives addressed at improving cooperation between primary care and psychiatrists could decrease AD prescription for cases of sub-threshold or mild depression that easily drop out because of rapid symptom relief or side effects.
European Journal of Clinical Pharmacology 08/2013; · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The results of an analysis of suspected antiviral-associated adverse drug reactions (ADRs) in Italy over a 22-year period are presented. METHODS: A case/non-case analysis was conducted using ADR reports compiled in the nationwide spontaneous-reporting database through September 2010. All reported events included in the analysis were evaluated and coded by drug safety experts; causality assessments were performed according to the algorithm of Naranjo et al. The association between an adverse reaction and antiviral use was assessed by estimating the reporting odds ratio (ROR), with 95% confidence interval (CI), as a measure of disproportionality. RESULTS: Overall, 863 reports of suspected ADRs involving antivirals and 42,430 reports of adverse reactions to other drugs were identified; of those events, 3.3% and 64.3% were determined to be definite or probable ADRs, respectively, and an additional 32.4% were deemed possibly drug related. Several ADRs were disproportionately associated with antivirals relative to other drugs: renal colic (ROR, 25.5; 95% CI, 13.3-49.0), lactic acidosis (ROR, 18.6; 95% CI, 9.2-37.7), depression (ROR, 18.0; 95% CI, 11.6-27.9), anemia (ROR, 15.9; 95% CI, 12.3-20.4), hallucination (ROR, 4.3; 95% CI, 2.7-7.1), neutropenia (ROR, 4.1; 95% CI, 2.9-5.8), acute renal failure (ROR, 3.9; 95% CI, 2.3-6.4), fever (ROR, 3.8; 95% CI, 2.8-5.1), hyperpyrexia (ROR, 2.9; 95% CI, 1.7-4.9), and asthenia (ROR, 1.8; 95% CI, 1.2-2.8). CONCLUSION: Analysis of data from a large Italian database showed that, among antiviral agents, the ribavirin-interferon combination, acyclovir, valacyclovir, indinavir, and zidovudine accounted for the most serious hematologic, neuropsychiatric, and renal ADRs.
American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 06/2013; 70(12):1039-1046. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Our aim was to evaluate whether dronedarone authorization impacts antiarrhythmic drug prescribing in Sweden and Emilia Romagna (Italy). METHODS: Prescriptions of classes I and III antiarrhythmics, expressed as defined daily doses per thousand inhabitants per day (DDD/TID) were monthly using information collected from pharmacy-reimbursed databases. Interrupted time series analysis was applied to compare prescription data over the 2009-2011 period. RESULTS: In Emilia Romagna, the overall consumption of antiarrhythmics was six times as high as in Sweden (7.6 vs. 1.2 DDD/TID). In the first year on the market, dronedarone represented 1.0 % in Italy and 10.7 % in Sweden of the overall antiarrhythmic prescriptions. In Sweden, dronedarone authorization generated an increase in the prescription trend of antiarrhythmics (trend change +0.02; p < 0.001) without variation in amiodarone use In Emilia Romagna, dronedarone marketing did not influence the prescription pattern of either overall antiarrhythmics or amiodarone. CONCLUSIONS: Emilia Romagna and Sweden substantially differ in terms of overall antiarrhythmic use. Although clinical guidelines place dronedarone among first-choice treatments for atrial fibrillation, amiodarone prescribing was not affected in either country by the entry of dronedarone, probably due to a cautious approach by clinicians in line with regulatory recommendations and safety warnings.
European Journal of Clinical Pharmacology 09/2012; · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : The risk of myocardial infarction, macular oedema and bone fractures associated with thiazolidinediones (TZDs) has been extensively investigated.
: The aim of the study was to verify if the analysis of a large spontaneous reporting database could generate early signals on these adverse drug reactions (ADRs) associated with TZDs.
: A case/non-case study, restricted to antidiabetic drugs, was performed on spontaneous reports of ADRs (2005-2008) in the US FDA Adverse Event Reporting System (AERS). The method was applied to TZDs, both as a drug class and as single agents. The reporting odds ratio (ROR) with 95% CI was calculated as a measure of disproportionality in the whole dataset and in a quarter-by-quarter analysis.
: TZD use was registered in 49 589 out of 301 950 drug-reaction pairs (16%), with significant disproportionality for myocardial infarction (ROR 4.71; 95% CI 4.40, 5.05), macular oedema (3.88; 2.79, 5.39) and bone fractures (1.73; 1.53, 1.96). Separate analysis of the two TZDs showed that only rosiglitazone was associated with myocardial infarction (7.86; 7.34, 8.34) and macular oedema (5.55; 3.94, 7.79), whereas pioglitazone was associated with multiple site fractures (2.00; 1.70, 2.35), in particular upper and lower limb and pelvic fractures. The quarter-by-quarter analysis identified disproportionality for myocardial infarction (3.13; 2.38, 4.10) and bone fractures since January-March 2005 (2.70; 1.04, 2.78).
: The frequency of reporting of myocardial infarction, macular oedema and fractures was significantly higher for TZDs in comparison with other antidiabetic drugs, with large intraclass differences. Both myocardial infarction and bone fracture signals appeared before major publications on these safety issues.
Drug Safety 02/2012; 35(4):315-23. · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications.
Case/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).
Ninety-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).
In 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.
Diabetes care 06/2011; 34(6):1369-71. · 7.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: At the end of 2006, a pharmacovigilance program on natalizumab was settled by the Italian Pharmaceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was documented.
[Show abstract][Hide abstract] ABSTRACT: At the end of 2006, a pharmacovigilance pro-gram on natalizumab was settled by the Italian Pharma-ceutical Agency, and on January 2007, multiple sclerosis patients poorly responding to the immunomodulating therapies or with an aggressive clinical form of disease from onset initiated to be registered and to receive the medication. On February 2010, almost 3,000 cases have been treated with natalizumab. The drop-out rate is 10%. Almost 800 cases received cycles of natalizumab for more than 18 months. One case of PML was reported and other adverse events are similar to those described in phase III studies. The majority of cases remained stable, while in 25% of cases, an improvement of disability was docu-mented.
[Show abstract][Hide abstract] ABSTRACT: In the general population, lack of adherence to statin therapy remains a widespread phenomenon and an important matter of concern both in terms of cost-effectiveness and risk-benefit profile. This study aimed to evaluate the occurrence of cardiovascular events in Italian statin recipients, focussing on the relationship between degree of adherence to therapy and occurrence of events in a 3-year follow-up.
Our cohort consisted of all patients from Emilia Romagna (4,027,275 inhabitants) who received statin prescriptions in January-February 2005 and who were followed for up to 36 months for cardiovascular hospital admission (i.e. coronary disease, cerebrovascular accidents, peripheral arthropathy), adherence to statin treatment (proportion of days covered: ≥ 80%) and use of other cardiovascular drugs. The relationship between adherence and cardiovascular events was analysed by multivariate logistic regression; age, sex, other cardiovascular drugs and previous events were covariates of the model.
Patients non-adherent to a statin regimen over the 3-year period (76% of the cohort) had higher odds of events, irrespective of risk factors, by more than 40% when compared with adherent patients. Odds of events were in particular: strongly non-adherent, adjOR=1.19 (CI95% 1.15-1.23), slightly non-adherent, adjOR =1.25 (1.21-1.30), highly variable in the amount of statins received, adjOR=1.69 (1.62-1.77).
This study shows the key role of adherence to statins in cardiovascular prevention at any level of risk. Appropriateness of statin use needs not only careful selection of patients to be treated, but also cooperation between patient and physician to ensure continued drug use whenever treatment is appropriate.
European Journal of Clinical Pharmacology 12/2010; 67(4):407-14. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.
We searched for drug-induced PML cases in two international spontaneous adverse drug reaction (ADR) report databases, FDA-AERS and WHO-VigiBase. From MEDLINE, we retrieved case reports and case series containing the MESH term "leukoencephalopathy, progressive multifocal/chemically induced". In order to assess the PML-drug relationship, we analysed drug-reaction pairs in terms of the patients' underlying diseases and co-suspected drugs.
Overall, 214 cases in FDA-AERS, 118 in WHO-VigiBase and 140 in MEDLINE were collected. Therapeutic groups more frequently involved in PML cases were monoclonal antibodies (MAbs), conventional immunosuppressive drugs and anti-HIV drugs. The most frequent underlying diseases were lymphoproliferative diseases (28%), autoimmune disorders (20%) and transplants (10%). MAbs were more often reported in cases where they were the only suspected drugs, whereas for the other therapeutic groups, concomitant drugs were reported.
We found a strong relationship between PML and MAbs, especially when used in autoimmune diseases. PML is becoming a crucial issue of MAbs, since they can cause severe ADRs through the imbalance of the immune system. Based on these results, patients treated with MAbs should be carefully monitored for early signs and symptoms of PML.
European Journal of Clinical Pharmacology 10/2009; 66(2):199-206. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: At the end of 2006 a country-based surveillance program on natalizumab therapy in multiple sclerosis was settled in Italy by a collaborative effort of the Italian Drug Agency (AIFA) and a group of experts and neurologists appointed by the National Society of Neurology (SIN). After 2 years, 1,818 patients are registered in the database. The majority of cases (88.6%) failed the therapy with beta interferon or glatiramer acetate and had relapses or accumulated disability during immunomodulating treatment, while 11.4% of patients enrolled in the surveillance study were not previously treated with immunomodulating therapies and had a rapidly evolving clinical course. Almost 10% of the patients treated with natalizumab interrupted, for various different reasons, the therapy. Treatment was well tolerated and side effects were similar to those reported in the registrative studies. The majority of treated cases are stable or ameliorated.
[Show abstract][Hide abstract] ABSTRACT: Natalizumab is a humanized monoclonal antibody with a selective adhesion-molecule inhibitor effect, and a demonstrated efficacy in decreasing the frequency of relapses and progression of disability in relapsing-remitting multiple sclerosis (RR MS). After the approval of FDA and EMEA in MS cases unresponsive to immunomodulating therapy or in severe MS patients also not previously treated with interferons, and considering the concern on the possible side effects, an accurate program of surveillance was organized in our country by a combined effort of AIFA, Cineca, Department of Pharmacology of University of Bologna, and a group of neurologists appointed by the National Society of Neurology (SIN). After 15 months from the authorization of natalizumab therapy in MS, as of 31 March 2008, 908 cases have been treated with natalizumab and enrolled in this pharmaco-vigilance study. The mean age is 35 years, while the duration of disease is longer and disability is higher than that reported in the registrative study. Side effects are at the moment mild and similar to those previously described. At follow-up, the majority of treated cases are stable or ameliorated. The treatment was discontinued in 6% of patients.