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.

Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials.

BACKGROUND AND OBJECTIVES: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. METHODS: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. RESULTS: The CVM study enrolled 658 first-dose vaccinees (children aged 5-11 years; n = 250 and adolescents aged 12-17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. CONCLUSIONS: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data.

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.

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.

Effects of Branched-Chain Amino Acids on Parameters Evaluating Sarcopenia in Liver Cirrhosis: Systematic Review and Meta-Analysis.

INTRODUCTION: Sarcopenia is a major element of malnutrition in liver cirrhosis (LC) and is present in 30-70% of this population, being associated with a poor overall prognosis due to related complications such as hepatic encephalopathy, ascites, and portal hypertension. This systematic review and meta-analysis aimed to evaluate the effects of branched-chain amino acids (BCAA) supplementation on several parameters used to assess sarcopenia in LC. MATERIALS AND METHODS: A comprehensive systematic electronic search was performed in PubMed, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov databases using predefined keywords. We included full articles that satisfied the inclusion and exclusion criteria. Quality assessment of included studies was conducted using Cochrane Collaboration's tool and NHLBI quality assessment tools for interventional and observational studies, respectively. The principal summary outcome was the mean difference (MD) in the evaluated parameters. We performed a pre- and post-intervention analysis and comparison between two intervention groups (BCAA vs. controls) of the evaluated parameters when applicable. RESULTS: A total of 12 studies involving 1,225 subjects were included in our qualitative synthesis and five in our quantitative synthesis. At baseline vs. post-intervention assessment, subjects receiving BCAA supplementation were found to have a significant improvement in skeletal muscle index (SMI) (-0.347 [95% CI -0.628-0.067; p-value 0.015]) and mid-arm muscle circumference (MAMC) (-1.273 [95% CI (-2.251-0.294; p-value 0.011]). However, no improvements were reported in handgrip (-0.616 [95% CI -2.818-1.586; p-value 0.584]) and triceps subcutaneous fat (1.10 [95% CI -0.814-3.014; p-value 0.263]). CONCLUSION: Following BCAA supplementation, several parameters used to evaluate sarcopenia in LC patients were found to be improved, including SMI and MAMC. Nevertheless, no improvements were seen in handgrip and triceps subcutaneous fat. Results should be interpreted with caution due to the limited methodological quality of the included studies.

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.

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.

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.

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.

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.

Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research.

Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1-Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism.

Safety Profile of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Hepatitis C in Romania: an Analysis Conducted in VigiBase®/ WHO.

BACKGROUND AND AIMS: Due to the increasing number of hepatitis C virus (HCV)-infected patients being treated with direct antiviral agents (DAAs) in Romania, we aimed to conduct a pharmacovigilance study in order to comprehensively evaluate the safety profile for the ombitasvir/paritaprevir/ritonavir and dasabuvir (Om/Pa/Ri+Da) regimen. METHODS: A retrospective analysis was conducted on the individual case safety reports (ICSRs), extracted from VigiBase® on 1 st February 2018, which included the Om/Pa/Ri+Da regimen as suspected for causing adverse drug reactions (ADRs). Potential drug-drug interactions (DDIs) were checked for all concomitant medication using the IBM Micromedex® tool. RESULTS: Among the 1,102 ICSRs retrieved, 260 were serious (23.5%). Ribavirin was significantly associated with more ADRs reported per case (on average 5.1 vs. 3.2 ADRs/case, p<0.001). Most commonly reported ADRs were pruritus (6.8%), fatigue (5.4%), dizziness (4.3%) and headache (3.8%). For the serious ICSRs, a significant relationship was found between age and renal and urinary disorders, and between gender and neoplasms, injury, poisonings and procedural complications. Hepatotoxicity was identified in six ICSRs, four of them being serious. Potential contraindicated DDIs were identified in 1.9% of all ICSRs and major DDIs in 20.4%. CONCLUSIONS: About a third of the ICSRs related to Om/Pa/Ri+Da regimen were serious. Pruritus, fatigue, dizziness and headache were the most commonly reported ADRs. The frequent use of multiple co- medications in HCV-infected patients requires the consideration of potential DDIs when using the Om/ Pa/Ri+Da regimen.

A description of medicines-related safety issues evaluated through a referral procedure at the EU level after 2012.

INTRODUCTION: Important drug safety issues are evaluated through a referral procedure in the EU by the Pharmacovigilance Risk Assessment Committee (PRAC) within the European Medicines Agency. We aim to describe all safety-related referrals assessed by the PRAC by June 2019. METHODS: Publicly available data on safety issues assessed through referral procedures that reached a final decision during July 2012-June 2019 were identified, analyzed and classified according to predefined criteria. RESULTS: Fifty-one safety issues were assessed by PRAC for 45 medicines/combinations/therapeutic classes during this timeframe. Referrals were initiated mostly by the European Commission (16) and France (8). Nine medicines were authorized in the last five years, the rest being well-established drugs. In four cases (flupirtine, hydroxyethyl-starch, valproate, codeine) PRAC re-assessed the same risks as previous recommendations have not been effective. Post-referral recommendations consisted of updates of the summary of product characteristics and package leaflet (42), Direct Healthcare Professional Communication (32), and other additional risk minimization measures (RMMs). Withdrawal was recommended for seven active substances. CONCLUSIONS: PRAC recommended routine or additional RMMs for most referrals. Complete withdrawal of a drug or withdrawal of certain pharmaceutical forms or concentrations was advised only when the risk could not be managed by RMMs.

Combined use of renin-angiotensin-aldosterone system-acting agents: a cross-sectional study.

Background Due to recent EU warnings and restrictions on the combined use of renin-angiotensin-aldosterone system (RAAS)-acting agents, and the seriousness of the associated harm, we analyzed the prescription of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) as dual therapy or associated with spironolactone. Setting An administrative claims database of a regional hospital in Romania. Methods We retrospectively included all adult patients hospitalized during 18 months in 2013-2014, discharged with a prescription of a RAAS-acting agent. Main outcome measures Counts of ACEIs and ARBs co-prescription, of ACEIs or ARBs combined with spironolactone, co-morbidities, co-medication, creatinine, and electrolytes assessment and values. Results Out of 1697 patients with a prescription of a RAAS-acting agent, 24 (1.4 %) were co-prescribed ACEIs and ARBs, and 416 (24.5 %) ACEIs or ARBs with spironolactone. Patients prescribed dual ACEI/ARB therapy and the ones with ACEI or ARB-spironolactone combination had significantly higher prevalence of increased creatinine level before discharge, compared to the ACEI and ARB monotherapy groups (48 and 31 % compared to 17 and 27 %). Subjects with diabetes, heart failure, ischaemic heart disease, or urea ≥40 mg/dL had higher odds of having ACEI or ARB-spironolactone combination compared to monotherapy, while hypertension and renal disease subjects had lower odds. Similar findings were comparing dual ACEI/ARB therapy to monotherapy except heart failure (not statistically significant). Conclusion Overall, the prevalence of use of dual therapy was low. The combined use of RAAS-acting agents was higher in patients with known risk factors for further renal function deterioration, compared to the ones without.

Statin drug-drug interactions in a Romanian community pharmacy.

BACKGROUND AND AIM: Statins are frequently prescribed for patients with dyslipidemia and have a well-established safety profile. However, when associated with interacting dugs, the risk of adverse effects, especially muscular toxicity, is increased. The objective of this study was to identify, characterize and quantify the prevalence of the potential drug-drug interactions (pDDIs) of statins in reimbursed prescriptions from a community pharmacy in Bucharest. METHODS: We analyzed the reimbursed prescriptions including statins collected during one month in a community pharmacy. The online program Medscape Drug Interaction Checker was used for checking the drug interactions and their classification based on severity: Serious - Use alternative, Significant - Monitor closely and Minor. RESULTS: 132 prescriptions pertaining to 125 patients were included in the analysis. Our study showed that 25% of the patients who were prescribed statins were exposed to pDDIs: 37 Serious and Significant interactions in 31 of the statins prescriptions. The statins involved were atorvastatin, simvastatin and rosuvastatin. CONCLUSIONS: Statin pDDIs have a high prevalence and patients should be monitored closely in order to prevent the development of adverse effects that result from statin interactions.

An insight into statin use and its association with muscular side effects in clinical practice.

BACKGROUND: Muscular complaints are known side-effects of statin therapy, ranging from myalgia to clinically important myositis and rhabdomyolysis. We investigated the statin use and association with the presence and characteristics of muscular complaints. METHODS: We conducted a prospective observational study in internal medicine departments. Patients with statin therapy before hospitalization were interviewed for muscular complaints. When muscular complaints were reported, information on type and severity of muscular symptoms, location and time to onset was collected. RESULTS: We identified 85 patients with statin treatment at hospital admission out of 521 included. Nine (10.59%) patients reported muscular complaints associated with statin therapy. A cluster of symptoms (cramps, stiffness, decreased muscle power) was reported, affecting both upper and lower limbs. The severity of pain was in most of the cases moderate or severe. All patients reported that pain was intermittent. Five reported that pain was generalized. Symptoms appeared in the first month of treatment or three months after the drug initiation. Creatine kinase was raised in one patient. In two cases drug interactions were probably responsible for muscular complaints. CONCLUSION: In the studied set of patients muscular symptoms were a rather frequent effect of statin therapy. As this side-effect could be troublesome for patients and could lead to more severe outcomes, their timely detection and management is important.

Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

INTRODUCTION: The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. METHODS: This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. RESULTS: In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. CONCLUSION: The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

Counseling provided by the pharmacist in Romanian community pharmacies: the patients' perspective.

BACKGROUND AND AIMS: Patient education is a critical task that may be carried out by the pharmacists, especially in the context of contemporary pharmacists' roles, which tend to be closer to patients and their needs. This study aimed to evaluate the counseling provided by the pharmacist in the community pharmacy, from the patient's perspective. PATIENTS AND METHODS: We conducted a prospective, non-interventional study in 520 pharmacies from 10 Romanian counties across the country. The first 10 visitors of the pharmacy on a given day were asked to complete a questionnaire regarding the counseling provided by the pharmacist during the visit. RESULTS: More than 90% of patients received advice from the pharmacist on the route of administration, use in relation to meals, dosage and length of treatment. More than 80% of the patients were counseled on the medicine contraindications and precautions, interactions with other medicines and food, side effects, additional changes in lifestyle and diet appropriate to the condition and the necessity to immediately consult a doctor/pharmacist in case of adverse drug reactions. Lower percentages were registered for advising the patient on the obligation to return to pharmacy the unused psychotropic drugs (38.04%) and the ability of the drug to modify the laboratory results (47.66). CONCLUSIONS: The results of the present study showed that the counseling activity in the community pharmacy is carried out by the pharmacists in a high proportion, according to the patients' feedback.

Preventability analysis of adverse drug reactions detected in two internal medicine departments in Romania.

In order to improve patient safety, systematic analysis of common and repetitive patterns of preventable adverse drug reactions (pADRs) in the clinical setting should be performed regularly in order to propose adequate prevention strategies. Our aim is to evaluate the preventability of all ADRs collected in a drug information research center database, by spontaneous reporting and clinical surveillance in two internal medicine departments. One reviewer systematically reevaluated all the cases stored in the database. ADRs were deemed preventable if they were due to: a contraindication, an inadequate dose, a drug interaction, an inappropriate prescribing decision for the patient's condition, inadequate monitoring, self-medication, or non-adherence to therapy. Out of 251 ADRs evaluated, 103 (41 %) were considered preventable. Out of the total pADRs, 86.4 % were serious. The most frequent adverse outcomes affected the gastrointestinal system (21.4 %), followed by the renal (11.6 %), metabolic (10.7 %), vascular (10.7 %) and hepatic (6.8 %) systems. Acenocoumarol (28 %), diclofenac (12.6 %), digoxin and furosemide accounted for more than 50 % of all preventable reports. One of up to three factors was involved in the preventability of the analyzed reports. Drug-drug interactions were the cause of 49.5 % of the pADRs. Inappropriate dose accounted for 17.5 % reports out of the total pADRs, inappropriate monitoring for 9.7 % reports, history of allergy to drug or drug class for 5.8 % reports and administration of a contraindicated drug for 4.8 % reports. Identifying prevalent pADRs in this study indicates a clear target for prevention strategies: drug prescription, with a special emphasis on drug interactions.