Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system.

Quadrivalent influenza vaccines (QIVs) are designed to prevent influenza disease caused by two influenza A viruses (H1N1 and H3N2) and both influenza B lineages. Risk-monitoring of QIVs to identify adverse events (AEs) is necessary as influenza vaccines are reformulated each year. We developed a new active surveillance system (Sistema de Control de Vacunación; SICOVA) to improve pharmacovigilance in Mexico. Participants (N = 2013) aged 0 - 96 years from nine sites across three influenza seasons (n = 1166 in 2015 - 2016; n = 633 in 2016 - 2017; and n = 214 in 2017 - 2018) agreed to receive text messages 1, 7, 28, and 42 days post-vaccination to know if they had experienced any AEs. The study was completed electronically by 1763 (87.6%) participants; manual follow-up was conducted for 250 participants whose reporting was incomplete. The overall AE rate was 9.09%. At least one AE was reported by 183 participants, of whom 131 (71.58%) did not require a medical visit and 52 (28.42%) needed medical attention, with none requiring hospitalization. Most AEs requiring medical attention occurred in children aged 0 - 5 years (n = 22, 42.31%) and adults aged 31 - 35 years (n = 5, 9.62%). These results are consistent with the established safety profile of Fluzone® Quadrivalent, and show that SICOVA can facilitate surveillance and increase AE reporting in Mexico.

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study

ABSTRACT Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

Post-marketing sampling and testing programs for licensed medicinal products: a narrative review

Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.

How were DTP-related adverse events reduced after the introduction of an acellular pertussis vaccine in Chile?

OBJECTIVES: To describe the trend in the frequency of adverse events (AE) records associated to pertussis component vaccines between January 1st, 2015 and June 30th, 2020 in infants younger than 2-years-old in Chile, by reviewing the records submitted to the AEFI NIP, stratified by DTP-vaccine type, wP or aP. MATERIALS AND METHODS: This was a retrospective observational study including all AEFI records of DTP (either aP or wP)-containing vaccines in the described sample. A descriptive analysis was performed according to vaccine type and AEFI, using MedDRA terminology. RESULTS: The total number of AEFI reports was 1,697: 815 corresponding to wP vaccines, 417 to aP vaccines, and 465 with unknown type. The reporting rates for the years 2015 to 2020 were 40.1, 56.2, 37.1, 24.7, 19.1, and 12.2 per 100,000 doses administered, respectively. The most reported AEFI were injection site erythema (42.9%), pyrexia (35.7%), and pain at the injection site (29.2%). Among all cases, 5.8% were SAEs (n = 98), 5.9% were SAEs for wP vaccines (n = 48) and 5.3% were for aP vaccines (n = 22). DISCUSSION: A significant decrease in AEFI reports was observed as of 2018, the year that the DTaP-IPV-HepB-Hib was introduced in the NIP.

Ophthalmic Solution Safety Profile: Active Surveillance of a Sodium Hyaluronate/Chondroitin Sulfate Combination in Peruvian Population.

BACKGROUND: Sodium hyaluronate/chondroitin sulfate fixed combination plays an essential role in the treatment of keratoconjunctivitis sicca, a multifactorial disease accompanied by ocular symptoms like alteration of the tear film. Despite low or no absorption of such drugs, these can cause secondary effects. An essential tool in the study of medication behavior is active pharmacovigilance. Unlike spontaneous reporting pharmacovigilance, this tool allows an appraisal of adverse drug reactions (ADRs)' real incidence, a higher capacity to identify safety signals, the relationship with concomitant drugs and pathologies prevalent in the study population. This study aimed to evaluate the safety profile and identify and/or assess adverse reactions in an uncontrolled population. METHODS: Active pharmacovigilance by Drug Event Monitoring was performed. A total of 3 follow-up calls were made for 30 days for the identification of the ADRs, tolerability (ADR severity, seriousness, long term sequelae, and duration) and the possible risks (safety signals, medical interactions) of sodium hyaluronate and chondroitin sulfate (HUM). RESULTS: Thirty-five ADRs were identified in the 212 patients included in the study (0.17 ADR/patient). The 35 ADRs were classified into 3 System Organ Class (SOC) groups: general disorders and administration site conditions (74.2%), eye disorders (22.9%), and nervous system disorders (2.9%); and 4 Preferred Term (PT) groups: burning sensation (74.2%), followed by blurred vision (20%), ocular pain (2.9%) and headache (2.9%). All the ADRs were categorized as mild and not serious. No statistically significant differences were found in concomitantly medications, posology and age groups. CONCLUSION: Good tolerability to the solution was identified, with a low incidence of ADRs. Just the same, all the associated ADRs were consistent with the information found in HUM's physicochemical profile and the physiopathology of DED. No unknown risks were identified, reinforcing HUM's safety profile.

The use of isotretinoin for acne - an update on optimal dosing, surveillance, and adverse effects.

INTRODUCTION: Acne is a chronic, inflammatory, and immune mediated disease of pilosebaceous unit, highly prevalent in adolescents. It involves face, trunk, and back; may leave scars and affect quality of life. Early, effective, and safe treatment is the key for disease resolution. Oral isotretinoin is the unique treatment for cure or prolonged remission for moderate and severe acne, preventing psychosocial impact and scars. It inhibits sebaceous glands activity and has anti-inflammatory and immunoregulatory properties. AREAS COVERED: We performed a comprehensive literature search on PubMed database, up to March 2020, regarding oral isotretinoin for acne treatment. We synthetized data about acne pathogenesis and mechanism of action, efficacy, and safety of isotretinoin. EXPERT OPINION: This drug is effective, despite common, controllable, and reversible mucocutaneous side effects. Serious adverse events are rare and represent individual reactions. Teratogenicity is the most severe, requiring rigorous control. We believe that no other therapeutic option, even topicals combined to oral antibiotics accomplish same results. Recurrence after treatments other than isotretinoin is the rule, prolonging risk of scars, compromising skin appearance, and causing emotional distress in teenagers. If there is no absolute contraindication, isotretinoin should be the first line treatment for moderate to severe inflammatory acne.

Commercially approved vaccines for canine leishmaniosis: a review of available data on their safety and efficacy.

Canine leishmaniosis is an important vector-borne zoonosis caused mainly by Leishmania infantum. Diagnosis and treatment of affected individuals can be particularly complex, hindering infection control in endemic areas. Methods to prevent canine leishmaniosis include the use of topical insecticides, prophylactic immunotherapy and vaccination. Four vaccines against canine leishmaniosis have been licensed since 2004, two in Brazil (Leishmune®, the production and marketing licence of which was withdrawn in 2014, and Leish-Tec®) and two in Europe (CaniLeish® and LetiFend®). After several years of marketing, doubts remain regarding vaccine efficacy and effectiveness, potential infectiousness of vaccinated and infected animals or the interference of vaccine-induced antibodies in L. infantum serological diagnosis. This review summarises the scientific evidence for each of the vaccines commercially approved for canine leishmaniosis, while discussing possible weaknesses of these studies. Furthermore, it raises the need to address important questions related to vaccination impact in Leishmania-endemic countries and the importance of post-marketing pharmacological surveillance.

La leishmaniose canine est une importante zoonose à transmission vectorielle causée principalement par Leishmania infantum. Le diagnostic et le traitement des personnes atteintes peuvent être particulièrement complexes, entravant la lutte contre l'infection dans les zones d'endémie. Les méthodes de prévention de la leishmaniose canine comprennent l'utilisation d'insecticides topiques, l'immunothérapie prophylactique et la vaccination. Quatre vaccins contre la leishmaniose canine ont été homologués depuis 2004, deux au Brésil (Leishmune®, dont la licence de production et de commercialisation a été retirée en 2014 et Leish-Tec®) et deux en Europe (CaniLeish® et LetiFend®). Après plusieurs années de commercialisation, des doutes subsistent quant à l'efficacité et à l'effet du vaccin, au potentiel infectieux des animaux vaccinés et infectés ou à l'interférence des anticorps induits par le vaccin dans le diagnostic sérologique de L. infantum. Cette revue résume les données scientifiques de chacun des vaccins commercialement approuvés pour la leishmaniose canine, tout en discutant des possibles faiblesses de ces études. En outre, il soulève la nécessité de répondre à des questions importantes liées à l'impact de la vaccination dans les pays où la Leishmania est endémique et à l'importance de la surveillance pharmacologique post-marketing.

Landscape analysis of pharmacovigilance and related practices among 34 vaccine manufacturers’ from emerging countries

Developing Countries’ Vaccine Manufacturers Network was tasked with the strategic goal of seeking solutions, jointly with manufacturers, for enabling the stable, sustainable supply of quality vaccines to developing countries to increase global immunization. As vaccines are given to millions of healthy people, including children, to prevent life-threatening diseases, vaccines must meet high safety standards. Vaccine safety monitoring is of paramount importance to maintain trust in vaccination programs globally. Once a vaccine is licensed and recommended for use, its safety and effectiveness must be monitored during its whole lifecycle, as the safety profile and protective effectiveness may change over time. A well-established safety governance model across the organization with underlying processes for data collection, signal and risk management and communication is essential. A "fit for purpose" pharmacovigilance system may vary as it depends on several factors. However, all vaccine manufacturers strive to achieve a pharmacovigilance system satisfying Good Pharmacovigilance Practices, in compliance with national, international and supranational requirements, as applicable. A landscape analysis, using a questionnaire covering nine pharmacovigilance key areas related to an effective system, was conducted to understand the existing pharmacovigilance structures, practices and expertise of vaccine manufacturers from emerging countries, on an institutional level. 34 of the 43 contacted manufacturers participated voluntarily. The survey results show that all respondents have established vaccine safety capacity, mainly in collecting and handling adverse events following immunization and implementing standardized processes; the survey also shows differences in the maturity of the manufacturers’ pharmacovigilance system, Quality Management System, signal and risk management, and safety governance. The analysis provides a tool for manufacturers to gain a "bird's-eye" view of the structure of pharmacovigilance key areas and the operational dimensions covered by each area, to benchmarking against international expectations, serving as a basis to further strengthen pharmacovigilance systems, to support accelerated global vaccine supply.

Nonadherence to treatment recommendations is a factor contributing to the clinical failure of daptomycin: Cohort study in Brazil

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11-21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

Post-marketing Drug Safety Evaluation using Data Mining Based on FAERS.

Healthcare is going through a big data revolution. The amount of data generated by healthcare is expected to increase significantly in the coming years. Therefore, efficient and effective data processing methods are required to transform data into information. In addition, applying statistical analysis can transform the information into useful knowledge. We developed a data mining method that can uncover new knowledge in this enormous field for clinical decision making while generating scientific methods and hypotheses. The proposed pipeline can be generally applied to a variety of data mining tasks in medical informatics. For this study, we applied the proposed pipeline for post-marketing surveillance on drug safety using FAERS, the data warehouse created by FDA. We used 14 kinds of neurology drugs to illustrate our methods. Our result indicated that this approach can successfully reveal insight for further drug safety evaluation.

Notificação de eventos adversos em vigilância sanitária: incompletitude das variáveis do NOTIVISA em 2007 E 2008. / Notification of adverse events in Sanitary Surveillance: variables incompleteness in Notivisa from 2007 to 2008.

A informação é instrumento fundamental para o processo decisório na vigilância póscomercialização/ uso, que tem por finalidade promover a identificação precoce de eventos adversos (EAs) relacionados com o uso de produtos sob vigilância sanitária. Este estudo avaliou aqualidade da informação, utilizando o indicador incompletitude das variáveis dos formulários das notificações de EA de uso de sangue e componentes (10), vacinas e imunoglobulinas (39), equipamentos (31) e artigos (30) médico-hospitalares recebidos pelo Notivisa em 2007 e2008. Trata-se de estudo transversal e descritivo. No ano de 2007, apenas 3 (30,0%); 6 (15,4%); 6 (19,4%) e 6 (20%) variáveis apresentaram taxa de incompletitude com classificação bom ouexcelente, respectivamente. Já em 2008, foram 4 (40,0%); 7 (17,9%); 7 (22,9%) e 7 (23,3%), porém as variáveis não foram as mesmas. Os resultados indicam que houve elevada incompletitude para a maior parte das variáveis estudadas. A instrumentalização para subsidiara vigilância pós-comercialização/uso está em construção no âmbito do Sistema Nacional de Vigilância Sanitária. Estratégias com melhoria do preenchimento das variáveis devem ser implementadas para contribuir com informações robustas na tomada decisão.

Information is essential to support the decision making process in post marketing surveillance. It aims to promote the early identification of adverse events (AE) related to the use of products under surveillance. This study aimed to evaluate information quality, using variables incompleteness of the notification forms of AE related to blood and its components use (10), vaccines and immunoglobulin (39), health care equipments (31) and medical devices (30) received by Notivisain 2007 and 2008. This is a transversal and descriptive study. In the year of 2007, only 3 (30%); 6 (15.4%); 6 (19.4%) and 6 (20%) variables presented incompleteness ratio with good or excellent classification, respectively. In 2008, there were 4 (40%), 7 (17.9%), 7 (22.9%) and 7 (23.3%), although the variables were not the same. The results indicate that the incompleteness for most of the studied variables increased. The instrumentation to subside the post marketing surveillance is still being constructed under the Sistema Nacional de Vigilância Sanitária (Brazilian national sanitary surveillance system). Strategies to improve the data s filling out must be implemented in order to provide relevant information to decision makers.

Tigeciclina: Una revisión sistemática de la experiencia clínica en sus primeros años de uso: [revisión] / Tigecycline: A systematic review of clinical experience during first years of prescription: [review]

The available clinical experience with tigecycline is analyzed under the perspective of a systematic review of the literature, so in the already approved indications as in those off label indications reported in the recent literature. The safety profile is checked in the above mentioned clinical trials. The available information allows supporting tigecycline efficiency in the managing of complicated skin and soft tissues infections, complicated intrabdominales infections and community acquired pneumonias. Its usefulness is insinuated in addition in the managing infection by pathogen with high-level of resistance to antimicrobial. Nevertheless it is needed of major evidence in the matter and of a very sensible policy of use in the healthcare institution setting.

Se analiza, bajo la perspectiva de una revisión sistemática de la literatura científica, la experiencia clínica con tigeciclina en las indicaciones ya aprobadas por las entidades reguladoras y en aquellas indicaciones off label reportadas en la literatura médica reciente. Se revisa el perfil de seguridad y tolerabilidad en dichos ensayos clínicos. La información disponible permite avalar su eficacia en el manejo de de infecciones de piel y tejidos blandos complejas, infecciones intrabdominales complicadas y neumonías adquiridas en la comunidad. Se insinúa además su utilidad en el manejo de infecciones por patógenos con alto nivel de resistencia a antimicrobianos. Sin embargo, se requiere de mayor evidencia al respecto y de una muy sensata política de uso en el medio hospitalario.

Vigilância pós-comercialização da Aguardente Alemã® (Operculina macrocarpa e Convolvulus scammonea) / Post-marketing surveillance of the Aguardente Alemã® (Operculina macrocarpa and Convolvulus scammonea)

A Aguardente Alemã (AA), produzida a partir dos extratos das raízes de Operculina macrocarpa e Convolvulus scammonia, conhecida, também, como “jalapa composta”, é indicadacomo laxante, mas é utilizada, popularmente, para as mais variadas patologias. Este trabalho objetivou delinear o perfi l do usuário desse fi toterápico, a forma de administração e as principais indicações de uso relatadas pelo usuário, utilizando, para isto, um questionário aplicado à população (n = 125) no momento da dispensação do produto em farmácias de Fortaleza, Ceará. Os usuários eram, na sua maioria, mulheres, com idade de 41 a 60 anos. A administração de AA era feita, em geral, com uma colher de chá (5 mL; 46,4%), uma vez por dia (87%), sem um horário fi xo de tomada; administrando com chá ou água, prioritariamente. A população referiuusar AA, principalmente, para problemas circulatórios (63%) e cefaléia (13,1%). A atividade purgativa, rotulada na formulação do produto comercializado, foi pouco referida. Desta feita, nossos resultados subsidiam importantes informações para o processo de certifi cação de AA junto às agências regulatórias e enfatizam a necessidade de mais estudos de vigilância póscomercialização, para a garantia do uso racional do produto pelo usuário.

The “Aguardente Alem㔠(AA), produced from extracts of the roots of Operculina macrocarpa and Convolvulus scammonea, also known as “composed jalapa”, is indicated as laxative, but it is used, popularly, for several diseases. Our objective was to delineate the user profi le of this herbal medicine, the way it is managed and the main use indications referred by users through a questionnaire applied to the population(n = 125) at the moment of the AA dispensing in community pharmacies of Fortaleza, Ceará. The users were mainly women, aged between 41 and 60 years. The administration of AA was generally done with a tea spoon (5 mL; 46.4%), once per day (87%), without an established time for taking; managing it with tea and water, principally. It was indicated by the population for using in diseases as circulatory problems (63%) and migraine (13.1%). The laxative activity, labeled in the formulation of the product, was poorly related. Thus, our results provide important information for the certifi cation process of AA to the regulatory agencies and emphasize thenecessity of more studies of post-marketing surveillance for the guarantee of the rational use of this product to the user.