An investigation on the association between sodium glucose co-transporter 2 inhibitors use and acute pancreatitis: A VigiBase study.

PURPOSE: To characterize acute pancreatitis (AP) related to sodium glucose co-transporter 2 inhibitors and to investigate this relationship through disproportionality analysis in an international pharmacovigilance database. METHODS: We analyzed all AP reports for canagliflozin, dapagliflozin and/or empagliflozin from the WHOs Global adverse drug reactions database VigiBase® up to July 2019. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR) and information component (IC) for each of the gliflozins. AP cases were reports containing at least one of 11 previously selected preferred terms. Gliflozin exposure was considered for all reports with at least one gliflozin as suspected/ interacting drug. RESULTS: Of the 19 834 180 individual case safety reports in VigiBase, in 600 reports containing 618 AP group reactions, gliflozins were suspected/ interacting drugs. Men were affected in 52.3% of the cases and 59.6% of the patients were in the 45-64 years age group. The reporters were in 417 cases healthcare professionals. Most of the reactions were reported for canagliflozin (59.7%), followed by empagliflozin (21%) and dapagliflozin (19.2%) and were serious (98.6%). Most of the reactions' outcomes (84% of the patients) were favorable. Ketoacidosis was frequently associated with the AP (21.3%). Significant PRR and IC were found for pancreatitis and pancreatitis acute for all three gliflozins, pancreatitis necrotizing for canagliflozin and empagliflozin and pancreatitis relapsing for empagliflozin. CONCLUSIONS: Most of the AP cases were serious and with favorable outcome. We identified possible alternative causes for AP, like concomitant medication, hypertriglyceridemia, and cholelithiasis and a frequent association with ketoacidosis. We found a significant association between AP and the use of canagliflozin, dapagliflozin, and empagliflozin that would need further investigation.

Drug utilisation study of antidiabetic medication during 2012-2019 in Romania.

BACKGROUND: To analyse the antidiabetic medication (ADM) market trends in Romania and to describe the utilisation of the new ADMs (glucagon-like peptide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase-4 inhibitors [DPP-4i] and sodium-glucose transport protein 2 inhibitors [SGLT-2i]). METHODS: We conducted an analysis of pharmacy claims data from IQVIA Romania. We analysed the reimbursed prescriptions that included at least one ADM as defined daily doses (DDDs)/1000 inhabitants/day and the number of prescriptions. RESULTS: The total number of ADMs DDDs/1000/day increased by 54.33% from 2012 (48.08) to 2019 (74.20). Biguanides, sulfonylureas and insulin were the most prescribed each year, with an increasing utilisation trend. In 2019 metformin represented 37.69% of the total market share, followed by sulfonylureas (29.94%) and insulin (23.93%). The newer antidiabetics uptake was low. In 2019 the number of DDDs/1000 inhabitants/day was 2.03 for DDP-4i, 2.39 for GLP-1 RA and 1.6 for SGLT2i. CONCLUSIONS: An overall trend of market increase was found for ADMs from 2012 to 2019, corresponding to the increasing prevalence of diabetes in Romania. Although the use of DPP-4i, GLP-1 RA and SGLT2i have increased steadily, the uptake remained low, with no more than 12.61% of the market share (alone or as fixed combinations with metformin or insulin) in 2019.

Study design, process and outcome indicators of post-authorization studies aimed at evaluating the effectiveness of risk minimization measures in the EU PAS Register.

Risk minimization measures (RMMs) represent an essential tool for preventing the occurrence of safety-related outcomes. The evaluation of RMMs effectiveness is essential to prove their success and ensure protection of public health. The aim of this qualitative review was to assess the design, process and outcome indicators used for attesting successful implementation of RMMs. We searched the EU Post-Authorization Studies Register up to 30 June 2018 for studies having the scope defined as 'effectiveness evaluation'. Study titles and objectives were screened to select the ones evaluating the effectiveness of RMMs. We described and assessed the extent to which these studies aligned with Good Pharmacovigilance Practices guidelines recommendations. Out of 360 registered studies, we identified 35 studies on evaluation of RMMs effectiveness, 29 being eligible for review. Twenty-six studies evaluated additional RMMs, employed in case routine interventions are considered insufficient. All studies assessed process indicators, five also assessing outcome indicators, thus using a dual-evidence approach as recommended by the guidelines. However, none of the latter used a pre-post design, comparing the frequency of the adverse outcome before and after the implementation of RMMs. Behaviour and knowledge were the most often assessed process indicators. Outcome indicators included occurrence of adverse reactions, pregnancy, off-label use and medication errors. Only four studies had an established threshold, all for process indicators. Stricter adherence to existing recommendations would allow for a more robust design for reaching established endpoints for RMM effectiveness evaluation. It would also infer harmonization, facilitate review and further more detailed guidance on conducting these studies.

Antispasmodic Effect of Essential Oils and Their Constituents: A Review.

The antispasmodic effect of drugs is used for the symptomatic treatment of cramping and discomfort affecting smooth muscles from the gastrointestinal, billiary or genitourinary tract in a variety of clinical situations.The existing synthetic antispasmodic drugs may cause a series of unpleasant side effects, and therefore the discovery of new molecules of natural origin is an important goal for the pharmaceutical industry. This review describes a series of recent studies investigating the antispasmodic effect of essential oils from 39 plant species belonging to 12 families. The pharmacological models used in the studies together with the mechanistic discussions and the chemical composition of the essential oils are also detailed. The data clearly demonstrate the antispasmodic effect of the essential oils from the aromatic plant species studied. Further research is needed in order to ascertain the therapeutic importance of these findings.

A Comparative Analysis of the Chemical Composition, Anti-Inflammatory, and Antinociceptive Effects of the Essential Oils from Three Species of Mentha Cultivated in Romania.

This work was aimed at correlating the chemotype of three Mentha species cultivated in Romania with an in vivo study of the anti-inflammatory and antinociceptive effects of essential oils. The selected species were Mentha piperita L. var. pallescens (white peppermint), Mentha spicata L. subsp. crispata (spearmint), and Mentha suaveolens Ehrh. (pineapple mint). Qualitative and quantitative analysis of the essential oils isolated from the selected Mentha species was performed by gas chromatography coupled with mass spectrometry (GC-MS). The anti-inflammatory activity of the essential oils was determined by the rat paw edema test induced by λ-carrageenan. The antinociceptive effect of the essential oils was evaluated by the writhing test in mice, using 1% (v/v) acetic acid solution administered intraperitonealy and by the hot plate test in mice. The results showed a menthol chemotype for M. piperita pallescens, a carvone chemotype for M. spicata, and a piperitenone oxide chemotype for M. suaveolens. The essential oil from M. spicata L. (EOMSP) produced statistically significant and dose-dependent anti-inflammatory and antinociceptive effects.

Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex in rats.

Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(η(6)-p-cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex.

Preventability of adverse effects of analgesics: analysis of spontaneous reports.

OBJECTIVES: The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. METHODS: This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. RESULTS: The 141 cases selected for the analysis included 16 cases of medication errors (11.3%) and 15 addiction cases (10.6%). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system disorders (26.6%), psychiatric disorders (15.0%), and skin and subcutaneous tissue disorders (12.1%). Tramadol alone or in combination (17.3%), followed by morphine (15%), fentanyl (9.8%), and paracetamol (8.7%) were the most frequently involved analgesics. More than half of the cases (54.6%) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95%): 51.5% were considered as preventable, 26.1% not preventable, and 22.4% not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients' risk factors when prescribing. CONCLUSIONS: A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients.

Unlocking protein-based biomarker potential for graft-versus-host disease following allogenic hematopoietic stem cell transplants.

Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT.

The Efficiency of Serum Biomarkers in Predicting the Clinical Outcome of Patients with Mesenteric Ischemia during Follow-Up: A Systematic Review.

The initial clinical manifestation of acute mesenteric ischemia poses a diagnostic challenge, often leading to delays in identification and subsequent surgical intervention, contributing to adverse outcomes. Serum biomarkers, offering insights into the underlying pathophysiology, hold promise as prognostic indicators for acute mesenteric ischemia. This systematic review comprehensively explores the role of blood biomarkers in predicting clinical outcomes during follow-up for patients with mesenteric ischemia. A thorough literature search across the PubMed, Cochrane Library, and EMBASE databases yielded 33 relevant publications investigating the efficacy of serum biomarkers in predicting outcomes for mesenteric ischemia. Numerous studies underscore the utility of blood biomarkers in swiftly and accurately differentiating between causes of mesenteric ischemia, facilitating a prompt diagnosis. Elevated levels of specific biomarkers, particularly D-dimers, consistently correlate with heightened mortality risk and poorer clinical outcomes. While certain serum indicators exhibit substantial potential in associating with mesenteric ischemia, further research through rigorous human trials is imperative to enhance their consistent predictive ability during the follow-up period. This study underscores the diagnostic and prognostic significance of specific biomarkers for mesenteric ischemia, emphasizing the necessity for standardized procedures in future investigations.

Prevalence and Risk Factors Associated with Potentially Inappropriate Prescribing According to STOPP-2 Criteria among Discharged Older Patients-An Observational Retrospective Study.

Pharmacokinetic and pharmacodynamic changes associated with old age, along with multimorbidity and polypharmacy might lead to inappropriate prescribing and adverse reactions. Explicit criteria such as the Screening tool of older people's prescribing (STOPP) are useful to identify potential inappropriate prescribing's (PIPs). Our retrospective study included discharge papers from patients aged ≥65 years, from an internal medicine department in Romania (January-June 2018). A subset of the STOPP-2 criteria was used to assess the prevalence and characteristics of PIPs. Regression analysis was performed to evaluate the impact of associated risk factors (i.e., age, gender, polypharmacy and specific disease). Out of the 516 discharge papers analyzed, 417 were further assessed for PIPs. Patients' mean age was 75 years, 61.63% were female and 55.16% had at least one PIP, with 81.30% having one or two PIPs. Antithrombotic agents in patients with significant bleeding risk was the most prevalent PIP (23.98%), followed by the use of benzodiazepines (9.11%). Polypharmacy, extreme (>10 drugs) polypharmacy, hypertension and congestive heart failure were found as independent risk factors. PIP was prevalent and increased with (extreme) polypharmacy and specific cardiac disease. Comprehensive criteria like STOPP should be regularly used in clinical practice to identify PIPs to prevent potential harm.

Utilization of psychotropic medicines in Romania during 1998-2018.

Background: Mental disorders can have a significant impact on patients' life, including economic, social and individual consequences, and psychotropic medication is essential to treat these conditions. Psychotropic drug utilization studies contribute to a clearer picture of the management of these conditions. Data published from Romania on this topic is limited. The present study aims to characterize the utilization patterns of anxiolytics, antidepressants (ADs), and antipsychotics (APs) in Romania during 1998-2018. Methods: Drug utilization data were provided by Management Center for Documentation, Information and Marketing (CEGEDIM) Romania and quantitative data for each psychotropic medicine were converted to total defined daily doses (DDDs) and to DDD/1000inhabitants/day (DDD/TID). The total use of medicines in DDD/TID was computed in order to obtain the drug utilization 90% (DU90%) segment. Results: An increasing trend in total utilization of psychotropic medicines in Romania started in 2004. Anxiolytics use was predominant until 2013 and the yearly anxiolytic use over the entire study period remained between 10 and 15 DDD/TID. Diazepam lost popularity over time in detriment of the utilization of other anxiolytic benzodiazepines, such as alprazolam and lorazepam. ADs utilization markedly increased during the study period (the average annual growth rate was 13.66% starting 1999). Selective serotonin reuptake inhibitors (SSRIs) became present on the 2008 DU90% and was the dominant class of ADs, with sertraline being the most prescribed, followed by escitalopram and paroxetine. APs utilization showed an increasing trend from 2003 until 2018. Atypical APs became present on the 2008 DU90%, while typical APs were no longer included in the 2018 DU90%. Among atypical APs, olanzapine was the main agent prescribed, and starting 2010 was followed by quetiapine and risperidone. The uptake of APs long-acting formulations became more evident during the last analyzed years (2015-2018). Conclusion: We observed an increasing utilization of APs and a more prominent increase in ADs utilization in Romania during 1998-2018. The anxiolytic prescribing remained nearly stable during this time. Further research can bring more information on the various factors influencing psychotropic utilization in Romania.

A VigiBase Descriptive Study of Fluoroquinolone-Associated Peripheral Nervous System Disorders.

BACKGROUND: Recent drug safety concerns described fluoroquinolone (FQ)-induced peripheral nervous system reactions. The objective of this study was to characterize such reports from VigiBase. METHODS: The analysis included FQ-induced peripheral nervous system disorder adverse drug reaction (ADR) reports (up to July 2019). We looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values, and descriptive analysis was performed for FQ-ADRs positive associations (ADRs, suspected FQs, potential risk factors, such as associated therapy and underlying disease). RESULTS: Disproportionality analysis revealed 4374 reports (3531 serious) with peripheral nervous system ADRs associated with at least three FQs (neuropathy peripheral, 5492; neuralgia, 481; polyneuropathy, 220; sensory loss, 99; peripheral sensorimotor neuropathy, 39). Among these, both time-to-onset and duration of reaction were mostly between 1-7 days and ≥30 days. Most of the ADRs were not recovered/resolved at the time of reporting. CONCLUSION: The results augment the existing data on FQ safety concerns, specifically their potential effect on the nervous system.

Safety Profile of Nutraceuticals Rich in Coumarins: An Update.

Coumarins are a family of benzopyrones largely distributed in the natural kingdom, being present in the seeds, fruits, flowers, or roots of various plant species. Natural coumarin compounds are found in significant concentrations in some herbs or spices used as nutraceuticals, but they are also present in cosmetics or household products, due to their pleasant odor. Therefore, an accidental exposure to high doses of coumarins, could lead to the development of harmful effects in some patients. This review summarizes the latest published data from preclinical and clinical studies with natural coumarins, focused on the investigation of general and specific toxicity, with the aim of a better understanding of the safety profile of these valuable compounds. Regulatory aspects concerning the use of natural coumarins in several world regions are also reviewed.

Concordance of pharmacist versus patient responses regarding counselling in community pharmacy.

RATIONALE AND OBJECTIVES: Patient counselling on medication is one of the activities that can and should be performed in community pharmacy. Patient counselling was proved to have a positive effect on clinical outcomes, quality of life, drug/disease knowledge, satisfaction and reduced health-service utilization. Our objective was to assess the degree of concordance between the responses of patient and pharmacist on the same questions regarding provided counselling. METHODS: Data from two questionnaires containing a common block of 14 questions regarding the counselling provided on the medications use, safety concerns, storage, validity term, disposal and disease monitoring was paired and analysed. Questionnaires were paired based on a code and Kappa Cohen coefficient (KCc) and the prevalence adjusted biased adjusted kappa (PABAK) were calculated to evaluate the degree of concordance between pharmacist versus patient responses. The values of the KCc and PABAK were interpreted as per Altman. RESULTS: For the 14 questions, data from 2047 to 2378 questionnaires collected from 520 community pharmacies in 10 of Romania's counties were analysed. The highest level of concordance ('very good') was achieved on the items regarding the counselling on the medicines' route of administration (PABAK = 0.88), time of administration (PABAK = 0.80) and dosage (PABAK = 0.82). The highest disagreement (week concordance) was found on the question regarding the counselling on the medicines adverse effects (PABAK = 0.01), where 44.8% of patients responded that they received counselling as compared to 93.1% of the pharmacists who responded that they offered counselling. For the rest of the questions, moderate concordance was found. CONCLUSION: Overall a moderate level of concordance between patient and pharmacist responses was found on the majority of the questions, with the highest level found for drug use (dosage, route and time of administration). The highest discrepancy was found for the counselling on the medicines adverse effects.

A Description of Acute Renal Failure and Nephrolithiasis Associated With Sodium-Glucose Co-Transporter 2 Inhibitor Use: A VigiBase Study.

Background: The Food and Drug Administration issued a warning on the risk of acute kidney injury and a signal of nephrolithiasis for patients using sodium-glucose co-transporter 2 inhibitors (SGLT2i). We performed a descriptive analysis on acute renal failure (ARF) and nephrolithiasis cases reported to SGLT2i in the VigiBase®, in the scope of characterizing the patients and reactions and to report on the disproportionality analysis. Methods: We analyzed all ARF and nephrolithiasis reports for SGLT2i in VigiBase from inception to September 2021. ARF cases were defined as reports containing at least one of the preferred terms (PTs) included in the ARF narrow Medical Dictionary for Regulatory Activities Standardised Queries (MedDRA SMQ). SGLT2i exposure was considered for reports with at least one gliflozin as a suspected/interacting drug. We characterized the patients, reporters, and reactions, and we present the proportional reporting ratio (PRR). Results: Of 27,370,413 total reports in VigiBase, we found 3,972 ARF reactions to gliflozins as suspected/interacting drugs in 3,751 patients and 231 nephrolithiasis reactions in 227 patients. Most cases were reported from American regions (3057; 81.49%), for patients of age group 45-64 years (1590; 59%). About 30% (1156) of the ARF reports were registered in 2018, most from spontaneous reporting, and from consumers followed by healthcare professionals (2,235; 61% and 1440; 38%, respectively). Canagliflozin was the most involved gliflozin in the ARF and nephrolithiasis cases (2,640; 67% and 109; 47%, respectively). The great majority of ARF and nephrolithiasis reports were serious (3,761; 95% and 182; 79%, respectively). Of the total ARF cases reported, 51 had fatal outcome, while 152 had not recovered/not resolved outcome. No fatal outcome was reported for nephrolithiasis. Disproportionality analysis in full database showed a PRR of 4.68 (95% CI 4.53-4.83) for all gliflozins-ARF and a PRR of 3.44 (95% CI 3.00-3.95) for all gliflozins-nephrolithiasis. Conclusion: Most of ARF reports associated with gliflozins were serious, with an important number of cases with fatal outcome. A drug safety signal was found between ARF narrow SMQ and gliflozins. Also, gliflozins were associated with an increase in the proportion of nephrolithiasis reports compared to other medications.

Relationship between beliefs about medicines and adherence in elderly patients with cardiovascular and respiratory diseases: A cross-sectional study in Romania.

OBJECTIVES: The aim of this study was to explore elderly patients' beliefs about medicines in general, and specific towards their treatment and the relationship between beliefs and adherence. METHODS: A cross-sectional study was performed by administering a questionnaire developed to meet the study's objectives. Elderly patients were recruited from three different settings. RESULTS: 167 patients agreed to participate to our study, having a mean age of 73 years. Patients were aware of the necessity for treatment, but they also showed concern over the potential for the adverse outcomes. Only 15% of the patients were completely accepting their treatment having high necessity and low concerns, while 40% were ambivalent, having high necessity beliefs, but also high concerns, with 89% being adherent in this group. Overall, higher adherence was significantly correlated with higher necessity and with higher necessity-concern differential. CONCLUSION: Patients beliefs have an impact on adherence, thus patients' concerns and necessities should be addressed in order to improve adherence and treatment outcome. PRACTICE IMPLICATIONS: Higher necessity positively influenced adherence to treatment, suggesting the fact that healthcare professionals could improve patients' adherence by outlining and educating the patients on the necessity of the treatment, while also managing patients' concerns.

Survery of healthcare professionals to assess the awareness, knowledge and self-reported behavior regarding recent fluoroquinolones safety issues.

Background and aims: The impact of fluoroquinolone (FQ)-induced long-lasting, disabling, and potentially irreversible serious adverse drug reactions (ADRs) on the overall benefit-risk balance and the need for adequate risk minimization measures has been recently assessed. The present study aims to evaluate physicians and pharmacists' awareness and knowledge of the recent safety issues communicated through a direct healthcare professional communication (DHPC), regarding FQs, at a national level, in Romania, as well as healthcare professionals (HPs) self-reported behavior regarding the management of the risk. Methods: Cross-sectional, online survey study, conducted in Romania. Results: A total of 127 participants responded to the survey. Six (4.7%) were physicians and 121 (95.3%) were pharmacists. The predominant age was 31-40 years (N=52, 40.9%), and most respondents were females (N=117, 92.1%). A majority of 101 (79.5%) were reportedly aware of the existence of the new safety issues associated with FQs, and slightly less were aware of the DHPC (N=86, 67.7%) issued in 2019. In terms of knowledge, slightly more than half of the respondents had correctly selected the responses regarding key safety messages on most important ADRs and restrictions / cautions for use. The impact of the communication on HPs self-reported behavior was high or very high in almost half of the participants (N=63, 49.6%). Conclusions: A high percentage of participants were aware of the FQ-associated safety concerns. Knowledge was relatively good for the key safety concerns among HPs. A notable impact on behavior was observed, mostly in terms of counselling of the patient and disseminating the information to colleagues.

Second-Generation Cephalosporins-Associated Drug-Induced Liver Disease: A Study in VigiBase with a Focus on the Elderly.

BACKGROUND: The objective of this study was to characterize individual case safety reports (ICSRs) and adverse drug reactions (ADRs) related to second-generation cephalosporins and resulting in hepatobiliary disorders, in VigiBase, WHO global database. METHODS: All second-generation cephalosporins hepatobiliary ADRs reported up to July 2019 were included. Characteristic of cephalosporins and ADRs, aside from disproportionality data were evaluated. RESULTS: A total of 1343 ICSRs containing 1585 ADRs were analyzed. Cefuroxime was suspected to have caused hepatobiliary disorders in most cases-in 38% of adults and in 35% of elderly. Abnormal hepatic function was the most frequent ADR, followed by jaundice and hepatitis. For 49% of the ADRs reported in the elderly and 51% in the adult population, the outcome was favorable, with fatal outcome for 2% of the adults and 10% of the elderly. Higher proportional reporting ration (PRR) values were reported in the elderly for cefotetan-associated jaundice, cefuroxime-associated acute hepatitis and hepatitis cholestatic as well as for cefotiam and cefmetazole-associated liver disorder. CONCLUSION: Hepatobiliary ADRs were reported for 2nd generation cephalosporins, with over 50% of cases in adults, without gender differences. Cholestatic hepatitis was predominately reported in the elderly and this category was more prone to specific hepatic reactions.

A VigiBase descriptive study of fluoroquinolone induced disabling and potentially permanent musculoskeletal and connective tissue disorders.

Recent drug safety concerns described fluoroquinolone (FQ)-induced serious musculoskeletal reactions. The objective of this study was to characterize reports with FQ-associated disabling musculoskeletal disorders, from VigiBase. The analysis included all FQ-induced musculoskeletal and connective tissue disorders adverse drug reaction (ADR) reports (up to July-2019), (disabling/incapacitating, or recovered/resolved with sequelae or fatal). We described aspects like reporter, suspected FQs, ADRs, associated corticosteroid therapy. We also looked into the disproportionality data in terms of proportional reporting ratio (PRR) and information component (IC) values. A total of 5355 reports with 13,563 ADRs and 5558 FQs were reported. The majority of reports were for patients aged 18-64 (62.67%), and the female gender prevailed (61.76%). Consumers reported almost half (45.99%), with a peak in reporting rates in 2017. Top reported ADRs were arthralgia (16.34%), tendonitis (11.04%), pain in extremity (9.98%), tendon pain (7.63%), and myalgia (7.17%). Top suspected FQs were levofloxacin (50.04%), ciprofloxacin (38.41%), moxifloxacin (5.16%), ofloxacin (3.17%) and norfloxacin (1.01%). For these, FQs-ADR association was supported by the disproportionality analysis. Corticosteroids were associated with about 7% of tendon related reports. The results augment the existing data on FQs safety concerns, specifically their potential effect on the musculoskeletal system.