Research on Construction of Pharmacovigilance System for Marketing Authorization Holders in China

Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.

Enlightenment from WHO Pharmacovigilance in Construction of Chinese Materia Medica Pharmacovigilance System

With the widespread concern about the safety of Chinese materia medica, China urgently needs to build a Chinese materia medica pharmacovigilance system that conforms to the national development policy and has the characteristics of traditional Chinese medicine(TCM). A good job of pharmacovigilance of Chinese materia medica not only helps Chinese pharmaceutical companies to control their risks, but also guides them to use drugs safely and rationally. And it is also of great significance to the national drug regulatory work. Based on the monitoring of herbal safety in WHO pharmacovigilance system, the establishment of a Chinese materia medica pharmacovigilance system was explored in order to provide a valuable reference for the risk control of Chinese pharmaceutical companies, the clinical use of Chinese materia medica, and the national drug regulatory work.

Importance of Pharmacoeconomics in the Pharmacovigilance for National Health Systems

The objective of this study is to conduct a literature review to assess the importance of pharmacoeconomics in developing pharmacovigilance activities as a working tool to guide the process of decision making in the health field. The authors have done a literature review in order to find information about pharmacovigilance and their relationship with the pharmacoeconomics field, as an important element to assess the economic and health consequences because of the use of drugs in health systems. From this study, it can be found that pharmaeoeconomics applied to the pharmacovigilance activities should be considered as an aspect that contributes to improving the rational use of medicines, because it allows to compare the costs and consequences （beneficial and detrimental） with the use of different pharmacotberapeutic alternatives, in order to assess the negative effects due to ADRs （adverse drug reactions）, which directly increase the morbidity and mortality in patients, increase the direct health costs and indirectly decrease the productivity labors. It can be also concluded that pharmacoeconomics constitutes an important aspect to the pharmacovigilance activity in the health systems, in order to evaluate the negative impact of ADR, both on patient health as its economic implications, due to associated costs with these adverse effects.

Why pharmacovigilance of traditional medicines used as analgesics is important?

Traditional remedies have gained recognition for their effectiveness in treating various conditions such as diabetes,arthritic pain,liver disease,cough and cold,memory enhancement,and immunological stimulation.Their perceived safety has led to the increasing use of herbs by people without prescriptions.These therapies remain significant in areas with limited access to modern drugs or cultural preferences for traditional treatments.With a long history of use,traditional medicines have been the primary method of pain management.This review article explores natural and herb-based analgesics,their origins,and potential benefits,along with the growing scientific evidence supporting their effectiveness.Studies have examined their efficacy in treating musculoskeletal pain,neuropathic pain,and migraines.Rather than being seen as separate therapies,traditional medicines should be considered supplementary or alternative options that can be integrated into comprehensive pain management regimens.However,some studies have reported adverse drug reactions associated with herbal formulations and plants.Therefore,there is a need for pharmacovigilance in traditional medicine to ensure patient safety and promote evidence-based practices.Although pharmacovigilance in this field is still developing,it faces challenges due to the wide availability of herbal medicines without on-site medical supervision.This paper discusses the complex challenges of herbal pharmacovigilance,provides insights on recent advancements,and offers recommendations for improving the safety monitoring of traditional medications in the future.

Defining the awareness and attitude of the clinicians through pharmacovigilance in Turkey

BACKGROUND Pharmacovigilance(PV)is the activities and scientific studies conducted to detect,evaluate,understand or prevent adverse reactions and other drug-related problems.AIM To define the awareness and experiences of the clinicians on PV and adverse drug reactions(ADRs)in Turkey.METHODS The study was cross-sectional and analytical.Data were obtained through a questionnaire.The questionnaire was sent via e-mail.The survey was sent to 2030 physicians and 670 participated.RESULTS The most appropriate definition of PV was correctly defined by 53.9%of the participants.The most important goal of PV was correctly defined by 54.9%of the participants,and 27.3%of the participants were aware of the Turkish Pharmacovigilance Center.Nonsurgical physicians had better PV knowledge than surgical physicians.A total of 80.9%of the physicians who encountered ADRs,filled in the ADR notification form,and 8.8%received training on how to fill in the form.PV knowledge of the clinicians was not sufficient.Although half of the physicians encountered ADRs,the rates of seeing and filling in the ADR form were low.CONCLUSION Few of the physicians followed the current information about PV.The results provide more comprehensive data on PV practices and ADR reporting at a national level.

Biguanides and lactic acidosis:unraveling the complex relationship

Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the risk of lactic acidosis associated with biguanide use have sparked considerable debate and scrutiny.This research article aims to provide a comprehensive analysis of the relationship between biguanides,particularly metformin,and lactic acidosis.We delve into the underlying mechanisms,epidemiological evidence,risk factors,clinical manifestations,diagnostic considerations,and management strategies related to biguanide-induced lactic acidosis.Additionally,we explore recent research developments,controversies,and future directions in this critical area of pharmacovigilance and clinical practice.

Antibiotics’ Prescribing and Pharmacovigilance Attitudes among Pediatricians and Pediatric Residents in Cyprus

Background: The inappropriate, irrational use or misuse of antibiotics is observed in all health systems and in all patients’ groups worldwide, especially for children, where antibiotics continue to be the drugs most commonly prescribed. Methods: A cross-sectional study was conducted in all public pediatric clinics in the Republic of Cyprus, from April to May 2015. A questionnaire was distributed to pediatricians in order to identify the antibiotic prescription practices in common childhood diseases and attitudes towards Pharmacovigilance. The SPSS 19.0 was used for the statistical analysis. In total 42 pediatricians and pediatric residents filled out the questionnaire. Results: A significant percentage of the respondents administered empirical therapy for possible group A streptococcus infection (59.5%), they implemented the “watchful waiting” tactic in acute otitis media (66.7%), whereas 11.9% of them administered antibiotics for the prevention of secondary respiratory tract infections. The majority of physicians did not feel diagnostic uncertainty leading to antibiotics prescribing (90.2%) and their prescribing habits were not influenced by parental demand (80.5%). Although 23.1% of physicians observed often/very often Adverse Drug Reactions (ADRs) after antibiotic administration during their clinical practice, however, 47.6% of the pediatricians declared that they did not report them. Conclusion: Health professionals’ continuing education on the use of therapeutic guidelines and protocols and the development of Pharmacovigilance programs could significantly contribute to the avoidance of the misuse of antibiotics in hospital care as well as to health professionals’ awareness on rational prescribing.

Does educational intervention change knowledge,attitude,and practice regarding pharmacovigilance among nursing officers in Central India?An interventional study

Objectives:To evaluate the impact of educational intervention on knowledge,attitude,and practice(KAP)regarding pharmacovigilance(PV)and adverse drug reaction(ADR)reporting among nursing officers.Materials and Methods:A pre-and post-single-arm interventional study was conducted at All India Institute of Medical Sciences(AIIMS),Nagpur from May 2021 to October 2021 among 48 nursing officers.Data related to KAP were obtained through validated questionnaires before and after 3 months of educational intervention.Results:The mean knowledge score among nursing officers significantly improved from 11.05±3.09 to 16.77±2.07 after training session(P<0.001).The mean score regarding attitude was significantly upgraded from 21.16±5.6 to 23.79±2.97(P<0.001).At baseline,the mean practice score was poor(2.41±2.89),which was improved after training session,but the difference is not significant.Conclusion:Educational intervention had a significant impact on knowledge and attitude toward ADR reporting.The practice of detecting and reporting an ADR to the treating consultant is improved,but it is not transformed into reporting an ADR to the PV center to a significant extent.Hence,it is recommended to streamline ADR reporting process by implementing such training modules more frequently.

Comparative Perception of Pharmacovigilance by Physicians versus Paramedical Professions in Ivory Coast

Objective: To assess the perception of pharmacovigilance by healthcare professionals practicing at the University Teaching Hospital of Cocody (Ivory Coast) in 2017. Methodology: A descriptive and analytic cross-sectional survey has been conducted in 2017 at the University Teaching Hospital of Cocody. This survey involved a sample of healthcare professionals practicing in 17 services who are prescribing medications and gave their oral consent. Results: A response rate of 54.08% (106/196) among physicians versus 43.87% (86/196) for the nurses and 27.61% (21/76) for the mid-wives. 57.94% (62/107) of paramedics versus 94.33% (100/106) of physicians had already heard about pharmacovigilance, during their basic training (40.18% of paramedics versus 73.58% of doctors). However, the main obstacles to the practice of pharmacovigilance were it teaching hours considered insufficient (94.39% of paramedics versus 75.47% of physicians), the lack of knowledge on the location of the pharmacovigilance unit (80.37% of paramedics versus, 40% of physicians) and the reporting of the adverse drug reactions to a hierarchical supervisor (60.60% of paramedics versus 37.25% of physicians). A regular visit of pharmacovigilance monitors in the hospital services (34.57% of paramedics versus 29.24% of physicians) and the availability of reporting forms (30.84% of paramedics versus 27.35% of physicians) could improve the perception of pharmacovigilance by the healthcare professionals. Conclusion: Our investigational survey has highlighted some factors that may influence the perception of pharmacovigilance by the healthcare professionals in Ivory Coast.

Analysis of Adverse Reactions Related to Drugs and Vaccines Received at the National Centre for Pharmacovigilance from 2009 to 2016 in Togo

Objectives: To assess the received suspected adverse events occurring upon treatment with drugs and vaccines, at National Centre for Pharmacovigilance, in Togo, from 2009 to 2016. Methods: A crossover study was conducted in order to collect data about patients, drugs, suspected adverse events and notifiers. Suspected adverse events were classified using Med DRA 19.1. Notification’s circumstances were classified into Public Health Programs’ campaigns and routine practice. Data were collated into Excel spreadsheet and processed with SPSS software. Key Findings: Regional distribution is irregular. Of the 322 collected report forms, paramedics have notified 60.8% of the cases. Adult patients were the most represented (70.2%). Public Health Programs campaigns provided 72.6% versus 27.4% for routine practice including Neglected Tropical Diseases (41.4%), immunization (27.7%), tuberculosis (25.9%) and 4.5% for HIV. Skin disorders were the most prevalent suspected adverse events (147 sheets;45.7%) followed by general disorders and administration site disorders (29.8%) and gastro-intestinal disorders (12.7%). General anti-infective drugs for systemic use, antiparasites, and insecticides were the most reported class of medications (161 sheets;44.7%). Conclusions: A thorough follow-up of pharmacovigilance launched activities is needed to build a sustainable adverse effect’s surveillance system and routine practice has to be strengthened.

Familiarity, Knowledge and Practices of Healthcare Professionals Regarding the Pharmacovigilance of Biological Medicines in Lusaka, Zambia: A Multi-Facility Cross-Sectional Study

Background: Pharmacovigilance of biological medicines is crucial because it ensures that medicines meet the World Health Organization (WHO) standards. In Zambia, there is little information on healthcare professionals’ familiarity, knowledge and practices on the pharmacovigilance of biological and biosimilar medicines. Therefore, this study investigated the familiarity, knowledge, and practices related to the pharmacovigilance (PV) of biological and biosimilar medicines at selected hospitals in Lusaka, Zambia. Methods: The study was an analytical questionnaire-based cross-sectional study conducted among healthcare professionals (HCPs) at the Adult hospital, Cancer Diseases hospital, Paediatrics hospital and Women and New Born Hospital in Lusaka. Data were collected over four weeks in May and June 2021 and subsequently analysed using IBM SPSS version 21. The statistical significance was set at a 95% confidence interval. Results: Of 245 participants, only 115 (48.9%) of the HCPs were familiar with biological medicines to a basic understanding. Regarding the term biosimilars, most of the HCPs (40.9%) never heard of this word. The mean score for knowledge regarding the PV considerations of biological medicines was 4.1 out of 8 questions. Most HCPs used non-proprietary names (44.2%) when prescribing, dispensing, or administering biological medicines. Additionally, more than half (57.3%) of HCPs did not record batch numbers when dispensing or administering biological medicines. Conclusion: Healthcare professionals were more familiar with the term biological medicines than biosimilars. Healthcare professionals generally scored poorly when their knowledge regarding the PV considerations of biological medicines was assessed. Thus, there is a need to provide adequate training and continuous professional development among healthcare professionals on the pharmacovigilance of biological and biosimilar medicines.

Perception of Pharmacovigilance by Nurses and Midwives of the Cocody University Teaching Hospital in Abidjan

Objective: To assess the perception on pharmacovigilance by the nurses and midwives at the University Teaching Hospital (CHU) of Cocody in 2017. Methodology: Descriptive and analytic cross-sectional study conducted in 17 services of the University Teaching Hospital (CHU) of Cocody using an anonymized and standardized questionnaire. Results: The response rate was 39.33% for the 86 nurses and 21 midwives with at least 10 years of professional experience (50.6%). 57.94% of the respondents (n = 62) have already heard about pharmacovigilance during their basic training (40.18%, n = 43). However, only 19.63% (21/107) of the respondents knew about the existence of a pharmacovigilance unit which they wrongly located to the pharmacy (11/21) of the CHU of Cocody. 40.18% of respondents (n = 43) had previously experienced an adverse drug reaction that was reported (76.74%, n = 33) to a hierarchical supervisor (60.60%, n = 20). The causes of non-reporting were either the frequent occurence (4/10) or the benign nature (2/10) of the adverse drug reaction. Specific actions to be taken (37.38%, n = 40) and a feedback (28.97%, n = 31) were the respondents’ main expectations for the stimulation of the reporting system. They also wanted the pharmacovigilance monitors to regularly visit their services (34.57%, n = 37) and to provide them with the reporting forms (30.84%, n = 33). Conclusion: Our study has allowed us to highlight the lack of knowledge of the pharmacovigilance and to identify certain factors that could improve the perception of the pharmacovigilance by the nurses and the midwives in Ivory Coast.

The Construction and Thinking of the National Sentinel Alliance for Adverse Drug Reaction Monitoring

Objective To briefly introduce the construction and operation of the National Sentinel Alliance for Adverse Drug Reaction(ADR)Monitoring,and provide reference for strengthening the safety monitoring of drugs after listing in China.Methods The literature research method was used to analyze the establishment and promotion measures of the National Sentinel Alliance for ADR Monitoring,and then some countermeasures and suggestions were put forward to enhance the construction of the alliance.Results and Conclusion The alliance based on Chinese hospital pharmacovigilance system(CHPS)has played an important role in ADR monitoring and reporting.Promoting the construction of the alliance can provide a new method for improving the scientific evaluation system and active supervision system of drug safety after listing.Therefore,the construction of alliances at the national and provincial levels should be strengthened.Besides,relevant laws and regulations must be improved to accelerate the research and development of information systems,which will deepen the active monitoring of the alliance continuously.

Assessing liver injury associated with antimycotics:Concise literature review and clues from data mining of the FAERS database

AIM: To inform clinicians on the level of hepatotoxicrisk among antimycotics in the post-marketing setting,following the marketing suspension of oral ketocon-azole for drug-induced liver injury(DILI).METHODS: The publicly available international FAERSdatabase(2004-2011) was used to extract DILI cases(including acute liver failure events), where antimycot-ics with systemic use or potential systemic absorptionwere reported as suspect or interacting agents. The re-porting pattern was analyzed by calculating the report-ing odds ratio and corresponding 95%CI, a measure ofdisproportionality, with time-trend analysis where ap-propriate.RESULTS: From 1687284 reports submitted over the8-year period, 68115 regarded liver injury. Of these,2.9% are related to antimycotics(1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics(including ketoconazole and the newer triazole deriva-tives voriconazole and posaconazole) and terbinafine(used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-market-ing signal of risk.CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is con-sidered, especially in critical poly-treated patients under chronic treatment.

Diabetic retinopathy and age-related macular degeneration: a survey of pharmacoutilization and cost in Calabria, Italy

The aged population is constantly growing, thus fostering an increase in age-dependent diseases. Among these, diabetic retinopathy (DR) along with age-related macular degeneration entails progressive vision loss. Since such conditions are associated with the proliferation of novel vessels, their pharmacotherapeutic management consists of the intravitreal injection of anti-vascular endothelial growth factor drugs, able to hinder the driving of vascular proliferation prompted by vascular endothelial growth factor. The humanized anti-vascular endothelial growth factor monoclonal antibody ranibizumab provided evidence for efficacy in several trials, hence earning approval by the US Food and Drug Administration for therapeutic use in all the stages of DR. Due to the lack of epidemiologic and pharmacoeconomic evaluation in the local Calabria Region context, the present retrospective observational study focused on prevalence of DR and age-related macular degeneration, treatment and cost of therapy with ranibizumab in 870 patients arriving to clinical observation at the "Mater Domini” University Hospital in Calabria, Italy from January 2014 to June 2017. Data were extracted from the database of ophthalmology ward and subjected to statistical analysis. The results suggest that the most frequent retinal diseases are age-related macular degeneration and DR and that the use of ranibizumab has been decreasing over the 4-year study period together with the associated cost per patient which was similar for both disorders. Therefore, appropriateness of treatment with drugs other than ranibizumab needs to be assessed in this setting and deep monitoring of pharmacologic treatment for retinal diseases is necessary to prevent or delay visual acuity decrease and complete vision loss. Study procedures were performed in accordance with the "Mater Domini” University Hospital ethical standards of the responsible committee on human experimentation.

Drug-induced liver injury and COVID-19:A review for clinical practice

Coronavirus disease 2019(COVID-19)consists of a systemic disease that can present many complications.The infection presents broad clinical symptoms and a high rate of transmissibility.In addition to severe acute respiratory syndrome,the patients manifest complications beyond the respiratory system.The frequency of liver damage in COVID-19 patients ranges from 14.8% to 53% of patients.One should pay attention to drug-induced liver injury(DILI)in patients with COVID-19,especially considering the off-label use of drugs in prophylactic and therapeutic regimens applied on large scales.This review aims to present relevant information on the medication used so far in COVID-19 patients and its possible hepatotoxicity.We reviewed liver damage in patients with COVID-19 on PubMed and Virtual Health Library to investigate DILI cases.Four studies were selected,involving the medicines remdesivir,tocilizumab and a pharmacovigilance analysis study.The hepatotoxicity profile of drugs presented in the literature considers use in accordance to usual posology standards for treatment.However,drugs currently used in the management of COVID-19 follow different dosages and posology than those tested by the pharmaceutical industry.The deficiency of uniformity and standardization in the assessment of hepatotoxicity cases hinders the publication of information and the possibility of comparing information among healthcare professionals.It is suggested that severe liver injury in COVID-19 patients should be reported in pharmacovigilance institutions,and physicians should pay attention to any considerable abnormal liver test elevation as it can demonstrate unknown drug hepatotoxicity.Liver disorders in COVID-19 patients and the use of several concomitant off-label medications—with a potential risk of further damaging the liver-should at least be a warning sign for rapid identification and early intervention,thus preventing liver damage from contributing to severe impairment in patients.

Self-medication with nutritional supplements and herbal over-the-counter products

In recent years,the popularity increased for nutritional supplements and herbal products.Prescription drugs,but not herbal therapies are paid by health insurances.They are sold over-the-counter(OTC)on the patients’own expense.However,there are potential risks of self-medication,e.g.incorrect self-diagnosis,severe adverse reactions,dangerous drug interactions,risk of addiction etc.They are often used by patients at their own discretion without knowledge of and control by their physicians.Certain users are at risk of intoxication.Multiple medications taken by older patients increase the risk for adverse drug reactions,drug-drug interactions,and compliance problems for this age group(polypharmacy).Herbals should be discontinued prior to operations to avoid interactions with anesthetics or anticoagulants.Herbal preparations may also be carcinogenic or interfere with cancer treatments.Pregnant women use various OTC preparations.However,in many cases,it is unclear whether their use is safe for mother or baby.Self-medication with herbals is also largely distributed among anxious and depressive patients,and patients with other conditions and symptoms.The popularity of herbal products has also brought concerns on quality,efficacy and safety.Cases of botanical misidentification,contaminations with heavy metals,pesticides,radioactivity,organic solvents,microbials as well as adulteration with chemical drugs necessitate the establishment of international quality control standards.Hepatotoxic effects have been reported for more than 300 plant species,and some commonly used herbs have been demonstrated to interact with Western medication.Health care professionals have a critical responsibility assessing the self-care ability of their patients.Databases are available for pharmacists with information on action,side effects and toxicities as well as herbdrug interactions.There is a need for established guidelines regarding the correct use of nutritional supplements and herbal OTC preparations(phytovigilance).Physicians,pharmacists,and other health care professionals have to counsel patients and the general public on the benefits and risks associated with herbal drugs.Information centers for consumers and general practitioners are needed,and convincing evidence on safety and efficacy of herbal products has to be demonstrated in placebo-controlled,double blind and randomized clinical trials.

Real-world studies: bridging the gap between trial-assessed efficacy and routine care

Even though randomized controlled clinical trials(RCTs)have been accepted as the gold standard for official assessment of novel interventions,there is a substantial gap between the efficacy observed in RCTs and the impact on clinical practice and in terms of patient benefit.While real-world studies(RWS)are emerging to confer valuable complementing evidence in this regard and beyond,the evolving role of RWS is yet to be agreed.This article delineates an updated profile of RWS covering effectiveness verification,rare adverse effects discovery,indication repurposing,to name a few.RWS tends not only to improve the efficiency of clinical investigations for regulatory approval,but also optimizes the whole-life cycle evaluation of biomedical/pharmaceutical products.

Overview of drug induced liver injury in Brazil:What is the role of public health policy on the evidence?

BACKGROUND Adverse drug reactions are responsible for increased costs and morbidity in the health system.Hepatotoxicity can be induced both by non-prescription drugs and by those used for chronic diseases.It is the main cause of safety-related drug marketing withdrawals and could be responsible for irreversible and fatal injuries.AIM To identify and to summarize Brazilian studies reporting the drug-induced liver injury.METHODS A systematic review of Brazilian studies was carried out until June 2020.It was found 32 studies,being 10 retrospective cohorts,12 prospective cohorts,5 crosssectional,3 case-control,one case series and one randomized clinical trial.In most studies were investigated tuberculosis patients followed by other infectious conditions like human immunodeficiency virus(HIV)and hepatitis C virus.The hepatotoxicity ranged from one to 57%,led by isoniazid,rifampicin,and pyrazinamide.Few studies reported algorithm to assess causality.In most studies,there were moderate outcomes and it was necessary drug interruption.However,few severe outcomes,such as chronic liver damage and liver transplantation were reported.RESULTS Twenty-two different criteria for hepatotoxicity were found.The great heterogeneity did not allow a meta-analysis.Standardization of parameter of drug-induced liver injury and greater effort in pharmacovigilance could contribute to learn more about drug-induced liver injury(DILI)’s epidemiology in Brazil.CONCLUSION The development of strategic public health policies seems to have an influence on the DILI scientific evidence in Brazil due to main studies are in HIV and tuberculosis line care,two strategic health policies in Brazil.

Escitalopram-induced hepatitis:A case report

BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of depression.It is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?study.CASE SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark urine.We tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic obstruction.The etiological study was negative,and an adverse drug reaction was the sole possible explanation.The patient was receiving treatment with escitalopram.Two days after its withdrawal,pruritus was resolved.Ten days after withdrawal,clinical jaundice disappeared.It took a month and three weeks after withdrawal for the patient to have normalized liver function tests.To our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable causality.In addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality analysis.All cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this toxicity.We found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven days.CONCLUSION Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotoxicity and cholestasis,generally within a week after initiation.Thus,escitalopram should be withdrawn immediately if an iatrogenic cause cannot be excluded.If its responsibility is ascertained,escitalopram should be consequently contraindicated.In addition,serotoninergic antidepressants in patients with nonsevere depression are ineffective and harmful.Finally,the Sm PC of escitalopram should be updated to alert for this risk and give clear clinical guidelines.