National Pharmacovigilance Centre Research Articles

Analysis of Reporting Adverse Drug Reactions in Paediatric Patients in a University Hospital in the Netherlands.

AimsThe risk to develop adverse drug reactions (ADRs) is high for paediatric patients. This is, amongst other reasons, due to the inevitable use of off-label and unlicensed medicines. Moreover, there is limited knowledge on ADRs in children. Thus, adequate recognition may be challenging. The lack of dedicated studies and the voluntary nature of pharmacovigilance systems used to gain insight into the characteristics of ADRs contribute to this problem. The goal of this study is to identify whether ADRs in paediatric patients are adequately documented by the medical team and whether they are subsequently reported to the national pharmacovigilance system.MethodsAll patients admitted to the paediatric medium care of the Radboudumc Amalia Children’s hospital during 1 month, and using one or more drugs, were included. Two researchers analysed retrospectively and independently the number of possible ADRs in the medical records. The ADRs were listed per paediatric subspecialty, to evaluate any differences in documentation and reporting of the ADRs. Subsequently, the causality, severity, and seriousness of the ADRs were assessed. The ADRs were categorised by system organ class and drug class. The national pharmacovigilance centre was consulted to check if there were any reports coming from our hospital and to collect the total number of reports.ResultsThe medical records of 301 patients were analysed, 81 patients were suffering from one or more ADRs. In total 132 suspected ADRs were found, divided among 19 different paediatric subspecialties. Numbers were too small to investigate the differences in ADR documentation. Of these found ADRs, 55% were not explicitly noted as such in the medical records by the treating physician. None of the ADRs were reported to the national pharmacovigilance centre. Most ADRs scored ‘possible’ in the causality assessment, were mild or moderate, and a small number were serious. The ADRs occurred in 25 different organ systems. In total 25 different drug classes were involved.ConclusionsThe results of the present study show that a large number of ADRs are not registered in the medical records and are not reported to the national pharmacovigilance system. Furthermore, it is shown that the number of ADRs occurring at our centre is much higher than the number reported to the national pharmacovigilance centre. Only an average of 513 ADRs in paediatric patients are reported per year nationwide, suggesting that there is extensive underreporting.

The Adverse Effect Reporting for the Most Commonly Used Antibiotics

Aim: Antibiotics save lives, but the excess use of antibiotics leads to more side effects. Patients benefit from medications but also complain about their adverse effects. This study aims to explore the reports of the adverse effects for the most commonly used antibiotics in Saudi Arabia.
 Methodology: The Data regarding the adverse events reports were collected from The National Pharmacovigilance Center in Saudi Arabia. The data include the major allergic reactions and gastrointestinal side effects for the most commonly used antibiotic classes.
 Results: The total number of allergic and gastrointestinal adverse effects in 2017 and 2018 for the included antibiotic drugs is 583 reports. The majority of the reports were for penicillin antibiotics (39.96) particularly Amoxicillin/Clavunate.
 Conclusion: The most common adverse effects of antibiotics are allergic and gastrointestinal effects. It is important to report any adverse drug reactions either by health care providers or patients to the Saudi Pharmacovigilance Center.

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita= $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient= 0.57, P < .001). Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.

The Adverse Effects Reporting of Antibiotic Induced Diarrhea

Introduction: In Saudi Food and Drug Authority, there is a center called National Pharmacovigilance and Drug Safety Center responsible for adverse events reporting. This study aims to demonstrate the antibiotic induced diarrhea reporting by National Pharmacovigilance and Drug Safety Center in Saudi Arabia.&#x0D; Methodology: This is a retrospective study about the reporting of diarrhea adverse effects caused by antibiotics. The data were collected from the adverse effects reports that were submitted to Saudi Food and Drug Authority in 2017 and 2018.&#x0D; Results: Gastrointestinal adverse effects reports were mainly for penicillin antibiotics. The major gastrointestinal adverse effect of penicillin was diarrhea (100 reports out of 147 reports for penicillin include diarrhea). Most of the diarrhea reports were caused by Amoxicillin/Clavulanate followed by Amoxicillin.&#x0D; Conclusion: One of the major adverse effects for antibiotics is diarrhea that is mainly occurred by penicillin antibiotics. The majority of cases of antibiotics-associated diarrhea are not serious, but still affect the patients’ quality of life. Therefore, it is important to increase the awareness regarding medications adverse effects and their reporting.

Enhancing Pharmacovigilance in Sub-Saharan Africa Through Training and Mentoring: A GSK Pilot Initiative in Malawi.

IntroductionPharmacovigilance (PV) systems to monitor drug and vaccine safety are often inadequate in sub-Saharan Africa. In Malawi, a PV enhancement initiative was introduced to address major barriers to PV.ObjectiveThe objective of this initiative was to improve reporting of adverse events (AEs) by strengthening passive safety surveillance via PV training and mentoring of local PV stakeholders and healthcare providers (HCPs) at their own healthcare facilities (HCFs).MethodsAn 18-month PV training and mentoring programme was implemented in collaboration with national stakeholders, and in partnership with the Ministry of Health, GSK and PATH. Two-day training was provided to Expanded Programme on Immunisation coordinators, identified as responsible for AE reporting, and four National Regulatory Authority representatives. Abridged PV training and mentoring were provided regularly to HCPs. Support was given in upgrading the national PV system. Key performance indicators included the number of AEs reported, transmission of AE forms, completeness of reports, serious AEs reported and timeliness of recording into VigiFlow.ResultsIn 18 months, 443 HCPs at 61 HCFs were trained. The number of reported AEs increased from 22 (January 2000 to October 2016) to 228 (November 2016 to May 2018), enabling Malawi to become a member of the World Health Organization Programme for International Drug Monitoring. Most (98%) AE report forms contained mandatory information on reporter, event, patient and product, but under 1% were transmitted to the national PV office within 48 h.ConclusionRegular PV training and mentoring of HCPs were effective in enhancing passive safety surveillance in Malawi, but the transmission of reports to the national PV centre requires further improvement.

National pharmacovigilance programs in Arab countries: A quantitative assessment study.

The aim of the pharmacovigilance (PV) process is to bring together all the much-needed information about various aspects of product safety or, in particular, the safety and vigilance of drugs as pharmaceutical products. This study aimed to investigate and provide an overview on the current situation and activities of the national PV centers in Arab countries. A cross sectional study was conducted between March and May in 2018. The current survey was adopted and modified from a study that used the questionnaire designed by the World Health Organization Collaborating Centre for International Drug Monitoring. The national PV centers of 22 Arab countries were invited to participate in this study. Descriptive analyses were conducted utilizing the analysis services provided by SurveyMonkey. In total of, 15 countries responded to our invitation (response rate: 68%). Most Arab countries started their PV program in the last decade, with Palestine implementing its program in 2017. Among the respondents, nine (60%) were members of the WHO International Drug Monitoring Program and were all users of the software provided by the WHO Uppsala Monitoring Center (VigiFlow or VigiBase), except Sudan. In 2017, a total of 27 502 reports were received by the centers in the studied countries, ranging from three reports received in Lebanon to a total of 7362 reports received by the national program of Algeria. An improvement was noticed among the national PV programs in the Arab countries. However, a considerable difference still exists among the countries in terms of the implementation and practice of PV.

Herbal pharmacovigilance in Nepal: challenges and recommendations

Traditional herbal medicine is widely used globally. Despite its extensive use, there are no proper regulations on standardization and use of herbal medicinal products. Nepal has a rich biodiversity and demography comprising of different socio-ethnic groups. Herbal medicines are utilized prominently in Nepalese communities. These herbal products may cause side effects and adverse effects, such as nephrotoxicity, neurotoxicity with the heavy metal toxicity associated with their powdered dosage forms. The side effects of using herbal products have been documented, such as bleeding with use of Ginkgo biloba and increase in blood pressure with use of Ephedra. Regulation of herbal products is essential to promote their optimal and rational use. Standard tools are available for assessing adverse effects of herbal products from health authorities, like the World Health Organization. In Nepal, self-medication practice using traditional herbal medicines is common and includes the concomitant use of allopathic. There is no focal point to address the regulatory issues on herbal products currently in Nepal. The Department of Drug Administration in Nepal is nominated as a national pharmacovigilance center and there are no reports on adverse events from the use of herbal medicines so far. However, not having any reports does not ensure the absolute safety and effectiveness of herbal products, so vigilance is warranted. Herbal pharmacovigilance is needed for Nepal to ensure safe and effective use of herbal medicines as the current pharmacovigilance ecosystem does not capture those cases. In the Nepalese context, the absence of reporting mechanisms may have underreported adverse cases of herbal products. The present opinion article aims to discuss the use of herbal products in Nepal, the challenges associated with the adverse reaction due to herbal medicines, and recommendations to overcome these challenges

Sex Differences in Adverse Drug Reactions of Metformin: A Longitudinal Survey Study.

IntroductionIn general, women more often experience metformin-associated adverse drug reactions (ADRs) than men.ObjectivesWe aimed to assess whether sex differences in reported ADRs for metformin are observed at different times after initiation, and to explore their concurrence with sex differences in the dose of metformin over time. This may guide future studies in assessing the involved mechanisms of sex differences in metformin-associated ADRs and may guide sex-specific management of ADRs in clinical practice.MethodsThis study has a longitudinal design using data about patients initiating metformin collected by the Dutch National Pharmacovigilance Center Lareb through their Intensive Monitoring program. Patients were asked to complete a web-based questionnaire six times after initiation (i.e., at 2 weeks, 6 weeks and at 3, 6, 9, and 12 months). The outcome variables were the proportion of patients reporting any ADR (primary) and the dose of metformin (secondary). Sex differences in the proportions of ADRs and in the dose were tested at each assessment using Pearson Chi-Squared tests and Wilcoxon rank-sum tests, respectively. Using Bonferroni adjustment for multiple testing, a p value < 0.01 was considered statistically significant.ResultsThe number of included patients was 1712 (40.9% women). Women reported an ADR more often than men, which was statistically significant at the assessment at 2 weeks (34% vs 25%, p < 0.001), and 6 weeks (37% vs 28%, p = 0.001) after initiation. In general, women were reported to be prescribed a lower dose than men, which became statistically significant at the 9-month assessment (p < 0.01).ConclusionsSex differences in reported ADRs were seen in the first weeks after metformin initiation, whereas statistically significant differences in self-reported prescribed dosing were observed after several months. Patients, in particular women, might benefit from being prescribed lower metformin doses at treatment initiation.Electronic supplementary materialThe online version of this article (10.1007/s40264-020-00913-8) contains supplementary material, which is available to authorized users.

Adverse drug reaction reporting practice and associated factors among medical doctors in government hospitals in Addis Ababa, Ethiopia.

IntroductionAdverse drug reactions (ADRs) are global public health problems. In its severe form it may cause hospital admission, morbidity and mortality. Early reporting of suspected ADRs to regulatory authorities is known to be appropriate measure toinsure health and safety of public form such adverse drug reaction of drugs. In Addis Ababa, there is limited information on ADR reporting practices among medical doctors. Hence, this study aimed to assess ADR reporting practices and associated factors among doctors in government hospitals in Addis Ababa.MethodsAn institution based cross-sectional mixed-methods study design was used. Data werecollected from 407 doctors using self-administered questionnaire and five key informants using semi-structured questionnaire from October 01 to December 31, 2017. Binary logistic regression and thematic analysis methods for quantitative and qualitative data analysis were used respectively.ResultsOnly 94(27.4%) of doctors had ever reported ADRs to national pharmacovigilance center. The study showed that sex (AOR = 3.51, 95% CI: 1.76–7.03), level ofeducation (AOR = 5.01, 95% CI: 2.23–11.28), work experience (AOR = 4.59, 95% CI: 1.21–17.40), existence of ADR reporting form (AOR = 3.96, 95% CI: 1.07–14.61) and reporting to respective marketing authorization holders (AOR = 21.41, 95% CI: 5.89–77.88) were significantly associated with ADR reporting practices. Poor awareness and training on risk of under-reporting, feeling that reporting is minor, absence of appropriate reporting tools, delay and/or absence of feedback on reported ADRs, overly burdened doctors, negligence, fear of legal liabilityand communication gap were cited by key informants as barriers for reporting practice.ConclusionsAdverse drug reaction reporting practice among doctors wasfound to be low. Sex, level of education, work experience, existence of reporting form and reporting to marketing authorization holderswere significantly associated with ADR reporting practice. In addition, there are gaps in availabilities of guidelines, reporting systems and structure, pre-service and in-service training, and awareness of doctors on impact of reporting. Hence, improving access to ADR reporting form, decentralize safety monitoring system, and conducting awareness training on ADR reporting are essential to improve the ADR reporting practice.

Evaluation of pharmacovigilance activities in the national HIV/AIDS, malaria, and tuberculosis control programs using the World Health Organization pharmacovigilance indicators

Introduction: Public health programs (PHPs) provide unique opportunities for addressing health issues in resource-limited settings. A major challenge to the implementation of existing PHPs in Nigeria is the absence of effective monitoring of the safety of medicines and vaccines. The introduction of the World Health Organization (WHO) pharmacovigilance (PV) indicators provides a useful tool to address this challenge. Objective: The objective is to assess the structures, processes, and outcomes of PV activities in three selected PHPs (the National Malaria, tuberculosis [TB], and HIV/AIDS) in Nigeria using the WHO PV indicators and identify possible challenges to achieving the outcomes. Materials and Methods: A cross-sectional mixed method study of the PV system in selected PHPs. Data sources were from the Federal Ministry of Health, the National PV Center (NPC), the National Malaria/TB, and HIV/AIDS Control Programs and official documents were reviewed. Data were collected quantitatively using the WHO PV and PHP indicator questionnaires and qualitatively using key informant interviews. Results: The basic structures and tools for carrying out PV activities in the PHPs were in existence but optimal implementation was lacking. Of the 790 adverse drug reaction (ADR) reports from the PHPs to the NPC ADR database, 77% were from the HIV/AIDS Control Programs, 14% from the malaria control program, and 9% from TB program. The interview with representatives of the different programs revealed a consensus of opinion around lack of adequate human resource for PV, poor funding, poor stakeholders' coordination to improve PV reporting across all three programs as well as in the NPC. Conclusion: This study highlighted the magnitude of suboptimal implementation of PV activities evident by the number of reports as against the expected.

Bibliometric analysis of adverse drug reactions and pharmacovigilance research activities in Nepal.

Background:Bibliometric analyses have been used previously to study the measures of quality and impact of research performed in several health-related areas such as adverse drug reactions (ADRs) and pharmacovigilance (PV), etc. This method can assess the research performance of publications quantitatively and statistically. There is no evidence of bibilometric studies analyzing ADRs and PV from Nepal. Therefore, the present study aimed to assess scientific output on ADRs and PV-related research activities in Nepal using a bibliometric analysis of publications from 2004 January to December 2018, that is, 15 years.Methods:A systematic search was conducted in PubMed, Web of Science, Google Scholar, Scopus and Nepal Journal Online (NepJOL) databases. ‘Adverse Drug Reactions‘ or ‘ADRs‘ or ‘ADR‘ or ‘Adverse drug reaction‘ or ‘AE‘ or ‘Adverse Event‘ or ‘Drug-Induced Reaction‘ or ‘Pharmacovigilance‘ or ‘PV‘ and ‘Nepal‘. The search covered 15 years (January 2004 to December 2018) of study on ADRs and PV in Nepal. Only articles retrieved from databases were included, whereas published/unpublished drug bulletins, pharmacy newsletters and thesis were excluded. The articles thus retrieved were recorded, and thereafter analyzed. Word count code was used for the analysis of keywords used in the retrieved articles.Results:A total of 124 articles were retrieved, with the highest rate of publications in 2006 and 2007, with 16 papers each. Among the articles, 10 (8.1%) were published in Kathmandu University Medical Journal (KUMJ). Single papers were published in 38 different journals. Brief reports (1.6%), case reports (31.2%), case series (0.8%), education forums (0.8%), letters to the editor (5.6%), original research articles (41.9%), review articles (9.7%), short communications and short reports (8.1%) on ADRs and PV were recorded. Out of 124 papers, 52 (41.9%) were original research publications. The majority (74.1%) of research was done in the category of ADR incidence, types, prevention, and management, followed by policy and suggestions for strengthening national and regional pharmacovigilance centers of Nepal (14.5%).Conclusions:During the study years, there was an increase in scientific publications on drug safety. A total of 124 published articles were found during bibliometric analysis of ADRs and PV research activities in Nepal.

Severe cutaneous adverse drug reactions manifesting as Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the national pharmacovigilance center in Nigeria: a database review from 2004 to 2017.

Background:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCARs). There is scant literature on the characteristics and causes of these conditions among the Nigerian population. Here, we describe the epidemiology, associated morbidity and mortality, and culpable drugs in SJS and TEN cases using the National Pharmacovigilance (NPC) database in Nigeria.Methods:A retrospective review of the NPC database was done to analyze SJS and TEN cases reported over a period of 14 years. Annual reports, age and sex of patients, type of reporter, suspects and concomitant drugs, time to onset (TTO) of the reactions, and outcome of SJS and TEN were evaluated.Results:The NPC received a total of 24,015 adverse drug reaction (ADR) reports. SJS and TEN accounted for 284 (0.1%) of the total reports, of which 254 (89.4%) were SJS and the remainder were TEN. Females (n = 184, 64.8%) and individuals aged 19–40 years (n = 181, 63.7%) were the most affected by SJS and TEN. Antiretrovirals, followed by antibiotics, were the most common drug classes reported to cause SJS and TEN, with nevirapine (n = 174, 40.7%) and co-trimoxazole (n = 143, 33.5%) being the most widely implicated drugs. Among patients with reported outcomes, 73 (28.7%) SJS and 3 (10.0%) TEN cases recovered without sequelae, at the time of reporting. Severity of the SCAR was reported for only 171 (69.0%) cases, of which 12 (4.7%) and 8 (26.7%) resulted in death (Grade 5) among SJS and TEN cases, respectively.Conclusions:Antiretroviral and antibiotics were the commonly reported offending group of drugs for SJS and TEN cases. Nevirapine and co-trimoxazole were the commonly reported suspect drugs. SJS and TEN were reported most frequently in females and in patients aged 19–40 years, indicating that drug surveillance and counseling in these groups of patients may be beneficial.

Orphan drugs—access and unmet needs in 194 countries and six regions: a comprehensive policy review with content analysis

BackgroundOrphaned because of low prevalence and barely recoverable medical costs, patients with rare diseases are disproportionately deprived of life-saving treatment. In China, an estimated 16·8 million patients suffer from rare diseases. This substantial burden could potentially be addressed through policies that optimise research and development, licensing, pricing, and reimbursement of orphan drugs. We aimed to review existing international orphan drug frameworks to inform policy formulation in China. MethodsPharmaceutical legislation, regulation, or policies related to the access and regulation of orphan drugs were examined from 194 WHO member countries and six regions. Relevant policies were identified through an internet search for governmental policy documents, email contacts to national pharmacovigilance centres participating in the WHO Programme for International Drug Monitoring, and a systematic literature search from academic publication databases. English publications were searched from PubMed, MEDLINE, Embase, Web of Science, and the Cochrane Library, and the search was updated to July 31, 2019. Findings171 drug regulation documents from 156 countries or regions and 77 full-text academic publications were retrieved and read in full. 89 (44·5%) of 200 countries or regions had documentation on orphan drug policy. 34 subthemes from content analysis were categorised into six policy themes: orphan drug designation, marketing authorisation, safety and efficacy requirements, price regulation, incentives that encourage market access, and incentives that encourage research and development. In the past 5 years, surges in the establishment of orphan drug policy were found in non-high income countries (ie, lower-middle-income countries, upper-middle-income countries, and low-income countries). InterpretationGlobally, patient access to orphan drugs has been boosted by government regulatory efforts and incentives. In China, priority review and tax reduction on orphan drug regulation are being initiated, along with the establishment of a national registry system for rare diseases, which are expected to positively effect patient access to orphan drugs. However, the current drug regulatory and insurance scheme in China still needs substantial improvement to achieve the accessibility and affordability of orphan drugs across the nation. A need for solid nation-wide epidemiological data on rare diseases, orphan drug designation, and systematic policy support is timely. FundingNone.

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences.

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014-2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

Pharmacovigilance systems in resource-limited settings: an evaluative case study of Sierra Leone

Few low and middle-income countries (LMIC) have fully operational pharmacovigilance structures, systems and legal framework to collect and collate safety data and evaluate the risks and benefits by active and passive approaches. However, in a LMIC such as Sierra Leone, the capacity to manage the risks by taking appropriate preventative actions to help inform therapeutic decisions, promote rational use of medicines, guide risk management and communications is gradually growing but yet to be fully optimized.This study sought to assess the current status of pharmacovigilance in Sierra Leone since it became the 87th member of the World Health Organisation International Drug Monitoring Programme. This study evaluated the pharmacovigilance system in Sierra Leone through a comprehensive and system-based approach that covered the national medicines regulatory authority, health facilities and public health programmes. A descriptive cross-sectional study design was employed. Using a convenience sampling method, 14 respondents from the national medicines regulatory authority, six health facilities and six public health programmes were interviewed.Data were collected using a validated metric instrument: Indicator-Based Pharmacovigilance Assessment Tool. A scoring system was used for the quantification of assessment results with a score greater than 60% indicating that an organization has structural and policy frameworks to collect and collate safety data in a national database and evaluate the risks and benefits by both active and passive approaches.The study findings showed that the national medicines regulatory authority scored 79% and thus met the standard requirements of pharmacovigilance. On the other hand, the health facilities and public health programmes scored less than 60% indicating the need to fully operationalise pharmacovigilance frameworks at these levels. The study further demonstrated that the national medicine regulatory authority which hosts the national pharmacovigilance centre had functional pharmacovigilance structures and processes with potential to providing leadership in the implementation of pharmacovigilance in Sierra Leone.

Patient preferences and expectation for feedback on adverse drug reaction reports submitted in Ghana.

Personalized feedback received for spontaneous adverse drug reaction (ADR) reports serves as motivation for future reporting and the effectiveness of the feedback is dependent on the medium used in delivering the information. Explore expectation for feedback from patients on ADR reports submitted to the National Pharmacovigilance Centre (NPvC) in Ghana and the preferred medium for receiving the feedback information. Cross-sectional study using structured questionnaire administered through face-to-face interview from August to September 2016 to patients selected by convenience sampling. Pearson chi-square (§2) or Fisher's exact test was used to determine associations between background variables such as age, gender and level of education. The response rate was 86.7% (n=442). Of the participants interviewed, 96.5% expected to receive feedback for ADR reports submitted. Age and level of education were the two variables significantly associated with patients' expectation for feedback.The preferred medium for receiving feedback in decreasing order of preference were, telephone call (60.4%), mobile phone short messaging services (23.0%), email (8.3%), face-to-face meeting (3.4%), personalized letter (3.4%) and publication in a newsletter (1.4%). Patients' expectation for receiving feedback for ADR reports submitted to the NPvC is in line with modern trends in communication. NPvC should explore these alternatives for providing feedback to patients. This study is limited to what patients' expectations and preferences were for receiving feedback on ADR reports submitted, additional study to further explore the type of information patients expect to be contained in the feedback will be useful to National Pharmacovigilance Centres. None declared.

Ciprofloxacin and risk of hypoglycemia in non-diabetic patients

BackgroundFluoroquinolones have been associated with hypoglycemia in patients taking diabetic medications, most commonly due to drug-drug interactions and other associated risk factors. Except for four published case reports, there are no studies that have found positive associations between ciprofloxacin and hypoglycemia. In all but one of the cases, ciprofloxacin was taken with other hypoglycemic drugs. Recently, the Eritrean National Pharmacovigilance Centre received a serious case of hypoglycemia with recurrent episodes in a young and healthy patient without diabetes following use of oral ciprofloxacin. The aim of the present study is therefore to assess the causal relationship between ciprofloxacin and hypoglycemia in patients without diabetes using the World Health Organization-Uppsala Monitoring Centre global adverse drug reaction database (VigiBase®).MethodsA search was made on the World Health Organization global adverse drug reaction database (August 15, 2018) using “ciprofloxacin” as the drug substance and “hypoglycemia” as the reaction term. Cases that used hypoglycemic drugs (patients with diabetes) concurrently with ciprofloxacin and those with a completeness score below 50% were excluded to control for confounders and to improve the strength of the data. Hill criteria were used to assess causation.ResultsA total of 35 cases of hypoglycemia reported since 1989 from 17 countries in patients without diabetes associated with ciprofloxacin use with a median time to onset of 4 days were retrieved. The cases have a median age of 64 years (interquartile range, 50–85) with a similar male–to-female ratio. Ciprofloxacin was the only suspect and the sole drug administered in 48.5% of the cases. In ten cases, hypoglycemia abated following withdrawal of ciprofloxacin, and reaction recurred in one case on the subsequent rechallenge. Hypoglycemia was marked as “serious” in 20 cases, and the outcome was fatal in two cases.ConclusionsThis assessment found a suggestive causal link between use of ciprofloxacin and hypoglycemia in patients without diabetes.

Sex differences in adverse drug reactions reported to the National Pharmacovigilance Centre in the Netherlands: An explorative observational study.

AimsWe aimed to assess and characterize sex differences in adverse drug reactions (ADRs) reported to the national pharmacovigilance centre in the Netherlands while considering differences in drug use.MethodsADRs spontaneously reported by healthcare professionals and patients to the Netherlands pharmacovigilance centre Lareb were used. Drug–ADR combinations reported at least 10 times between 2003–2016 for drugs used by ≥10,000 persons in that period were included. Data about the number of drug users was obtained from the National Health Care Institute. Sex‐specific ADRs, like gynaecological problems, were excluded. Sex differences in specific drug–ADR combinations were tested using bivariate logistic regression analyses in which the number of drug users per sex was taken into account.ResultsIn total, 2483 drug–ADR combinations were analysed. Possibly relevant sex differences were shown in 363 combinations (15%). Most of these drug–ADR combinations were reported more often for women (322 combinations). Drugs with the highest number of ADRs that were more often reported for women included thyroid hormones (32 combinations) and antidepressants (16 combinations for the centrally acting sympathomimetics; 14 combinations for other antidepressants). Some ADRs were predominantly reported for women across a range of drugs such as headache and dizziness whereas other ADRs such as tendon ruptures and aggression were reported more often for men.ConclusionsIdentified sex differences in reported ADRs often referred to women. These differences may have various causes, including pharmacological and behavioural causes, which need to be further assessed. The results may ultimately lead to sex‐specific prescribing or monitoring recommendations.

Drug safety and Pharmacovigilance: An overview

Adverse drug reactions (ADRs) have a major impact on public health, reducing patient’s quality of life and imposing a considerable financial burden on the health care systems at a time when many health care systems are under considerable financial strain. All healthcare providers have roles to play in maintaining a balance between a medicine's benefits and risks. Once a drug is available to the public, making a determination about its safety is the shared responsibility of all who are part of the prescribing process, including patients. The role of healthcare professionals is vital in recording and reporting suspected ADRs in order that regulatory agencies are alerted of emerging safety concerns and thereby facilitating timely and appropriate action. Pharmacovigilance is an important exercise for monitoring of drug related issues after marketed in “real world setting”. Pharmacovigilance and all drug related issues are important for everyone whose life is being impacted any way by medical interventions. The evolution of Pharmacovigilance in recent years has growing importance as a science critical to effective clinical practice and public health science. The national Pharmacovigilance centers have become a significant influence on the drug regulatory authorities, at a time when drug safety concerns have become increasingly important in public health and clinical practice. This paper unfolds the basics of drug safety and other important aspects of Pharmacovigilance. Keywords: Adverse drug reactions, Pharmacovigilance, Drug regulation.

A Retrospective Review of Serious Adverse Drug Reaction Reports in the Nigerian VigiFlow Database from September 2004 to December 2016.

Adverse drug reactions (ADRs) are a source of concern in healthcare as they negatively affect patients. Serious adverse drug reactions (SADRs) have an even greater impact on patients and the system in terms of morbidity and financial burden. The establishment of National Pharmacovigilance Centers (NPCs) has enhanced ADR reporting in Africa. The Nigerian Pharmacovigilance Centre has been collecting ADR reports using VigiFlow since 2004. The aim of this study was to identify and analyze SADR reports in the Nigerian VigiFlow database in order to profile the patients with SADRs, the medicines most implicated, system organ classes (SOCs) affected, outcome of such reactions, including fatalities, and ADR reporting trends over the years. We also looked at the data elements provided in the reports as a proxy measure of report quality. We retrospectively assessed all individual case safety reports (ICSRs) received by the NPC in Nigeria and entered into VigiFlow as SADR reports between September 2004 and December 2016. We defined SADR as any untoward reaction to any medicine dose that resulted in death, required in-patient hospitalization or prolongation of existing hospitalization, resulted in congenital anomaly, persistent or significant disability/incapacity or was life-threatening. The suspected SADRs were analyzed at the Medical Dictionary for Regulatory Activities SOC and Preferred Term levels. A total of 11,222 ICSRs were entered into VigiFlow during the study period, of which 298 (3%) were classified as SADR reports. Adults were the most affected (244/282; 87%). The median number of medicines per report was 3 (interquartile range = 2-4.75). Nevirapine (36/336; 11%), as a single entity, was the most reported medicine. Human immunodeficiency virus (HIV) infection affected 128/232 (55%) of those with SADRs. There was no statistically significant association between the number of reactions per report and sex of the patients (p = 0.280), their age groups (p = 0.670), or the number of medicines per report (p = 0.640). Hospitalization was the most frequently cited reason for classifying a report as serious (151/276; 53%) and death was reported in 48 cases (48/283; 17%). Based on the SOC, skin and subcutaneous tissue disorders (139/550; 25%) was the most affected, while anemia (55/550; 10%) was the most reported specific reaction. A substantial number of patients (107/256; 42%) either recovered fully or were recovering from the SADRs. The number of SADR reports received varied by year with no consistent trend. There is under-reporting of ADRs in the Nigerian VigiFlow® database, particularly SADRs and those involving pediatric and geriatric age groups. Given that over half of the SADR reports involved antiretroviral drugs, it is imperative to increase the surveillance of ADRs related to this class of drugs through regular clinical assessment of reports and provision of feedback on the findings to healthcare providers. Direct consumer reporting should also be encouraged as a means of increasing ADR reporting.