1,721,163 research outputs found
Six-year activity on approval of compassionate use of medicines by the Ethics Committee of the University Hospital of Bologna (Italy): time to update rules and recommendations
No full textPurpose: Compassionate use of forthcoming drugs has become an increasing pathway through which patients can take advantage of promising medicines. We aimed to analyse the main features of the requests of compassionate use submitted to the Independent Ethics Committee (IEC) of the University Hospital of Bologna in the period 2010â2015. Methods: The present analysis concerns the requests of compassionate use received by the IEC in the period 2010â2015. For each requested drug, we paired the date of the first request to our IEC with the date(s) of (a) submission to EMA, (b) CHMP positive opinion, and (c) European marketing authorization (if issued). Results: In the period 2010â2015, our IEC received compassionate use requests for 610 patients. Most of the requests concerned patients suffering from solid or haematological cancers not responsive to first or second line of treatment. Sixty-five couples of medicine/clinical condition (corresponding to 56 individual medicines) were submitted to our IEC, and 62 of them regarded products following the centralised procedure at the EMA. Twenty-one out of the latter (34%) had already obtained CHMP positive opinion. Conclusions: Our results indicate that compassionate use of forthcoming medicines represents a not negligible portion of the therapies utilized in hospital care. The observed large resort to medicines still on trial may suggest that doctors are more aware with the potential benefits of the new drugs. However, this trend may also indicate an increasing marketing activity of the pharmaceutical industry, addressing to get the clinicians used to the upcoming medicines
Postmarketing safety of migraine prophylactic monoclonal antibodies: An EudraVigilance database analysis of eptinezumab, fremanezumab, galcanezumab, and erenumab
Full text linkObjectives/Background: This study was undertaken to evaluate the postmarketing safety of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide pathway used for migraine prophylaxis through pharmacovigilance data analysis by examining suspected adverse events reported in Europe. Migraine is one of the most prevalent and debilitating neurological disorders globally. The introduction of mAbs targeting the calcitonin gene-related peptide pathway has transformed migraine prophylaxis. However, their safety profiles in real-world settings are not fully established, and ongoing safety monitoring is essential, as clinical trials may not capture all potential adverse drug reactions associated with new therapies. Methods: A disproportionality analysis was carried out by analyzing postmarketing pharmacovigilance data from the EudraVigilance database, focusing on four mAbs: eptinezumab, fremanezumab, galcanezumab, and erenumab. Descriptive and statistical analyses were performed on data retrieved from the date of marketing authorization of each medicine up to June 16, 2024. The reporting odds ratio (ROR), information component, and empirical Bayes geometric mean were calculated to detect signals of disproportionate reporting comparing their safety profiles to topiramate, a standard preventive migraine treatment. Results: A total of 14,285 reports had emerged; most of them were from females and concerned patients aged 18–64 years. The most frequently reported adverse drug reactions were primarily nonserious, aligning with literature and previously established safety profiles, such as fatigue and injection site reactions. The statistical analysis revealed 15 significant disproportionality signals: 11 for eptinezumab and four for galcanezumab. Eptinezumab highlighted potential new safety signals such as palpitations (ROR = 6.93, 95% confidence interval [CI] = 3.39–14.18), oropharyngeal pain (ROR = 7.19, 95% CI = 3.40–15.24), and erythema (ROR = 12.31, 95% CI = 4.58–33.12). These findings suggest a potential class effect, warranting further investigations and highlighting the importance of continued monitoring regarding the long-term safety of mAbs. Conclusion: Almost all of the most reported and statistically significant adverse events were nonserious and consistent with the existing literature. Given the chronic nature of migraine treatment, continuous pharmacovigilance monitoring is essential to ensure their constant safe use in clinical practice
Comparative Safety Profiles of Oncology Biosimilars vs. Originators in Europe: An Analysis of the EudraVigilance Database
Full text linkSimple Summary Nowadays, biosimilar drugs are numerous and widely used in many clinical fields, including oncology. However, skepticism remains towards these products among doctors and patients, particularly regarding their safety profile compared to the reference products. This prompted this comparative pharmacovigilance study using real-world clinical data. Consistent with the expected similarity in safety, our results reaffirm that biosimilars are comparable to the reference products in the real-world setting. This should further reassure and encourage their even greater use which, on the one hand, allows for all patients to be treated with the best available treatments and, on the other, frees up healthcare resources for innovative and more expensive drugs. In the last decades, the clinical management of oncology patients has been transformed by the introduction of biologics. The high costs associated with the development and production of biologics limit patient access to these therapies. The expiration of exclusive patents for biologics has led to the development and market introduction of biosimilars, offering the reduction of costs for cancer treatments. Biosimilars are highly similar to the reference products in terms of structure, biological activity, efficacy, safety, and immunogenicity. Therefore, the monitoring of biosimilars' safety in real-world clinical practice though pharmacovigilance is essential. This study aimed to analyze the post-marketing pharmacovigilance data of biosimilar monoclonal antibodies used in oncology and compare them with respective reference products. Data of a 2-year period (1 January 2021-31 December 2022) were retrieved from EudraVigilance, and descriptive and comparative analysis were performed using the Reporting Odds Ratio to evaluate the distribution of medicine-reaction pairs related to biosimilars of three antitumor biological products and their corresponding reference products: bevacizumab, rituximab, and trastuzumab. The results showed that most frequently reported ADRs for biosimilars were non-serious and consistent with the safety profiles of reference products. These findings provide reassurance regarding safety equivalence of biosimilars and support their use as valid alternatives to originator biologics
Prescriptions of antidepressants in primary care in Italy: pattern of use after admission of selective serotonin reuptake inhibitors for reimbursement
No full textSafety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions
No full textAim: Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Methods: Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P â¤Â 0.05 were statistically significant. Results: We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P â¤Â 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47â1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28â0.34)]. We identified other potential signals that have not been associated with DOACs previously. Conclusions: As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred
Drug-Induced Progressive Multifocal Leukoencephalopathy: A Comprehensive Analysis of the WHO Adverse Drug Reaction Database
No full textObjective To identify safety signals concerning the association
between the use of various drug classes and the onset
of progressive multifocal leukoencephalopathy (PML).
Methods All reports containing suspected or interacting
PML-related or leukoencephalopathy-related drugs, held in
the World Health Organization spontaneous individual case
safety reports database as at 1 September 2014, were
retrieved.Weidentified safety signals by analysing the drug–
reaction pairs, using the reporting odds ratio as a measure of
disproportionality. A safety signal was defined if a drug was
reported more than twice in PML cases with a reporting odds
ratio[2 and a lower 95 % confidence limit[1.
Results We retrieved 2452 reports associated with PML
(N = 1612), leukoencephalopathy (N = 835) or both
(N = 5), corresponding to 343 different drugs. PML was
reported similarly in male and female adults (18–64 years),
and almost 30 % of the cases had a fatal outcome. The
most frequent Anatomical Therapeutic Chemical (ATC)
classification groups concerned antineoplastic agents
(23.5 %), antivirals for systemic use (10.1 %) or
immunostimulants (4.6 %). Significant disproportionality
was found for 88 drugs in the overall analysis (of cases with ‘progressive multifocal leukoencephalopathy’ or
‘leukoencephalopathy’ as the Preferred Term), and a new
safety signal was identified for 59 active substances (e.g.
muromonab-CD3, basiliximab and antithymocyte Ig), as
no information on a possible risk of PML was acknowledged
in their Summary of Product Characteristics documents.
Some safety signals were confirmed also after
sensitivity analysis adjustment for several confounding
factors (underlying diseases and considering only ‘progressive
multifocal leukoencephalopathy’ as the Preferred
Term).
Conclusion We report a possible association between
several drugs and PML that has not been previously
described. In addition, we have confirmed previously
reported signals in a number of drugs. We highlight the
need for follow-up by regulatory agencies
Off-label use of nicardipine as tocolytic and acute pulmonary oedema: A post-marketing analysis of adverse drug reaction reports in EudraVigilance
No full textPurpose: To evaluate a signal of acute pulmonary oedema (APO) due to nicardipine used off-label as tocolytic in pregnant women. Methods: All the suspected cases of APO recorded in EudraVigilance database up to 31/01/2013 and associated with nicardipine containing medicinal products were retrieved. The Proportional Reporting Ratio was considered as measure of disproportionality. Individual cases evaluation was conducted. Results: Thirty-four spontaneous cases regarding pregnancy women who experienced APO following nicardipine treatment as tocolytic were collected. The detected proportional reporting ratio was 50.96 (95% confidence interval lower bound equal to 36.75). The analysis focused on 10 serious cases. Most women, aged between 27 and 39 years, were treated with intravenous nicardipine. The most of the suspected adverse reactions occurred between 24 and 96hours. Conclusions: A potentially causal association between APO and off-label use of nicardipine as tocolytic has been detected during a periodic signal detection activity. The Pharmacovigilance Risk Assessment Committee confirmed our findings, recommending an update of the summary of the product characteristics for medicines containing nicardipine for both intravenous and oral formulations. Then European Medicines Agency reaffirmed that nicardipine use in other indications is no longer recommended
SIFIF: SISTEMA DI INFORMAZIONE E FORMAZIONE INDIPENDENTE IN FARMACOVIGILANZA
No full textProposta di sistema di formazione e informazione indipendente sulla Farmacovigilanza in Itali
Signal detection activity on EudraVigilance data: analysis of the procedure and findings from an Italian Regional Centre for Pharmacovigilance
No full textBackground: In July 2012 a new European legislation (Directive 2010/84/EU and Regulation No. 1235/2010) regarding pharmacovigilance has become effective. It has boosted the activity of Signal Detection through a monthly analysis of potential safety signals on EudraVigilance (EV). Our aim is to describe the procedure of signal detection on EV data and to present results obtained by the our pharmacovigilance centre. Method: Data are extracted from EV database, which collects suspected Adverse Drug Reactions (ADRs) of medicinal products in Europe. We are appointed to supervise digoxin, nicardipine, delapril, manidipine and hydrochlorothiazide/ramipril. ADRs are coded through MedDRA Preferred Terms and collected in the electronic Reaction Monitoring Report (eRMR). Statistical analysis is based on the Proportional Reporting Ratio (PRR) as a measure of disproportionality. Results: Up to April 2016 we have analyzed 45 eRMR for each drug. Two signals for nicardipine were submitted to the Pharmacovigilance Risk Assessment Committee of European Medicines Agency (EMA): acute pulmonary oedema (off-label use as tocolytic) and thrombocytopenia. Conclusions: Our experience shows the scientific and regulatory value of signal detection activity on EV data in order to continuously evaluate the benefit/risk profile of recent and older drugs
Comparative Safety Profiles of Biosimilars vs. Originators Used in Rheumatology: A Pharmacovigilance Analysis of the EudraVigilance Database
Full text link: Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug-event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology
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