Postmarketing Surveillance Program Research Articles

Sthavar Visha- Need of Balance in Tradition and Safety

The ancient Indian system of medicine has a long history of using poisonous herbs and minerals, known as Sthavar Visha, which are an integral part of Ayurveda medicines used for therapeutic purposes. It involves a delicate balance between harnessing the medicinal properties of these substances and mitigating their potential risks. These toxic substances can be transformed into beneficial medicines through meticulous processing, while the improper use of Sthavar Visha can lead to significant toxicity and may cause harm instead of causing benefits. This manuscript explores the diversity of Sthavar Visha, the challenges of complex formulations, variability in quality, and the lack of standardized dosages. Case studies on Aconitum ferox (Vatsanabha) and mercury-based preparations highlight the measures of potential dangers along with their solutions. Addressing these risks requires stringent quality assurance, substantial research and clinical trials, effective regulatory oversight, and increased education and awareness. Pharmacovigilance in Ayurveda, although currently underutilized, plays a crucial role in monitoring adverse effects and ensuring the safety of Ayurveda practices. Effective regulatory oversight is crucial for monitoring the use of potentially toxic substances and ensuring compliance with safety standards. Implementing post-marketing surveillance programs and encouraging adverse event reporting can help identify potential safety concerns and take timely corrective actions. Combining traditional knowledge with safety methods is essential for promoting health and ensuring quality treatment in Ayurveda's growing global popularity. A harmonious integration of tradition and safety measures will pave the way for a robust and sustainable future for Ayurveda medicine.

Quality of antiretroviral, antimalarial and antituberculosis medicines in Zambia: Findings of routine post-marketing surveillance.

There is growing concern in sub-Saharan Africa that poor-quality antimicrobial medicines may negate management of infectious diseases of public health importance should they fail to meet the set criteria of quality, safety and efficacy. The objective was to ascertain the quality of antiretroviral, antimalarial and antituberculosis medicines supplied and available in the public health sector in Zambia. A descriptive cross-sectional study was conducted involving the analysis of data from the continuous routine in-country post-marketing surveillance programme in Zambia that assessed the quality of antiretroviral, antimalarial and antituberculosis medicines supplied to public healthcare facilities between January 2018 and June 2023. Data were extracted from laboratory quality analysis results from samples collected as part of routine post-marketing surveillance by the Zambia Medicines Regulatory Authority between January 2018 and June 2023. The samples were collected from various levels of the pharmaceutical supply chain across Zambia. Samples were analysed according to their respective pharmacopoeia standards at the Medicines Control Authority of Zimbabwe Quality Control Laboratory, a World Health Organization prequalified laboratory. Data were extracted using a structured Excel database and analysed using Microsoft Excel, and GraphPad Prism Software was used for visualizations. Of the 198 samples, 86 (43.43%) were antiretrovirals, 54 (27.27%) antimalarials and 58 (29.29%) antituberculosis medicines. Of these 198 samples, 171 (86.36%) originated from Asia, 19 (9.60%) Africa and 8 (4.04%) Europe. All sampled medicines met their respective quality specifications with respect to tests, which included appearance, identification, assay, uniformity of mass, weight variation, disintegration, dissolution, pH and specific gravity, giving a compliance rate of 100%. Antiretrovirals, antimalarials and antituberculosis medicines obtained from public healthcare facilities in Zambia through routine post-marketing surveillance met their quality standards. This might positively impact treatment outcomes for HIV/AIDS, malaria and tuberculosis. There is a need for large-scale continuous monitoring of the quality of medicines in order to ensure quality is maintained and substandard products removed from the pharmaceutical supply chain.

Adverse events following immunization (AEFIs) with anti-meningococcus type B vaccine (4CMenB): Data of post-marketing active surveillance program. Apulia Region (Italy), 2019–2023

The four-component recombinant-DNA anti-meningococcus B vaccine (4CMenB) has been approved by the European Medicines Agency in 2013. In Italy, 4CMenB is recommended since 2017 for use in infants under one year of age. Due to the strong evidence of increased risk of fever after administration, surveillance of adverse events following immunization (AEFIs) is a priority for 4CMenB.This cross-sectional prospective study aims at investigating 4CMenB’s safety profile. The study population is represented by infants under twelve months of age vaccinated with 4CMenB in selected ambulatories in Apulia, a region in South-Eastern Italy, from October 1st, 2020, to March 31st, 2023. Parents were provided with a post-vaccination diary covering up to seven days after immunization and were contacted one week after the vaccination day. Information about AEFIs was collected, and reactions were classified following World Health Organization guidelines. For serious AEFIs, causality assessment was carried out. AEFI risk determinants were investigated via logistic regression.A total of 4,773 diaries were completed, with 78.13 % of them (3,729/4,773) containing one or more AEFI reports. Systemic reactions such as malaise, drowsiness/insomnia and fatigue were the most common ones, followed by fever and local pain, tenderness, redness and swelling.Twenty-three cases of serious AEFIs were reported. Following causality assessment, 78.26 % of serious adverse events (18/23) were deemed to have a consistent causal association with the administration of 4CMenB (reporting rate: 0.38 %). Three infants were hospitalized following vaccination, but no cases of death or permanent/severe impairment were reported. Prophylactic paracetamol administration showed a significant protective effect against the risk of manifesting fever within the first 24 h after administration (OR: 0.75; p < 0.005).Our data confirms existing evidence regarding the safety of 4CMenB vaccination in babies under 2 years of age, but also highlight a significant risk of fever after vaccination. Prophylactic paracetamol administration could represent a protective factor against fever, especially during the first 24 h after vaccination.

Adverse Events During Dosing of Delayed-release/Extended-release Methylphenidate: Learnings From the Open-label Phase of a Registration Trial and a Real-world Postmarketing Surveillance Program

PurposeDelayed-release/extended-release methylphenidate (DR/ER-MPH) (formerly HLD200) is an evening-dosed agent used for the treatment of attention-deficit/hyperactivity disorder. Postmarketing surveillance data from approximately 74,000 patients exposed to DR/ER-MPH (up to June 17, 2022) were reported and compared with the open-label, treatment-optimization phase of a Phase III clinical trial to derive possible learnings on how to approach adverse events (AEs) that emerge during dose titration. MethodsAn analysis of AEs spontaneously reported to Ironshore in postmarketing surveillance included, where available, age, dose, timing, and discontinuations. Data were summarized using descriptive statistics. FindingsA total of 395 children, adolescents, and adults reported 601 AEs in postmarketing surveillance. Five AEs were classified as serious. AEs preceded drug use discontinuation in 172 patients. Many AEs occurred early (52% were reported within 30 days) and at lower doses (54% were reported at 20 to 40 mg), similar to the trial data. Reported AEs included those similar in type but orders of magnitude lower in number than those from the clinical trial. ImplicationsNo new safety concerns were revealed in this real-world setting compared with the safety profile identified in DR/ER-MPH trial data. In real-world practices, clinicians tended to discontinue DR/ER-MPH treatment after AE onset, whereas trial investigators continued to optimize treatment and found that AEs were generally tolerable, suggesting that health care practitioners may consider developing strategies to manage tolerability issues with DR/ER-MPH treatment on AE emergence rather than immediately discontinuing use of the drug to provide optimal therapeutic benefit. ClinicalTrials.gov identifier: NCT02493777.

EPH140 Safety of PDE-5 Inhibitors for Erectile Dysfunction: Descriptive and Disproportionality Analyses of the FDA Adverse Event Reporting System (FAERS) Database from 2010 to 2022

Phosphodiesterase type 5 (PDE-5) inhibitors are often used as a first-line therapy for erectile dysfunction (ED). This study identifies characteristics of adverse events (AEs) and any potential safety signals associated with PDE-5 inhibitors used for ED from a post-marketing safety surveillance program.

Assessment of adverse events for a home-use intense pulsed light hair removal device using postmarketing surveillance.

Home-use intense pulsed light (IPL) hair removal devices are convenient for consumers. Consumer safety associated with home-use IPL devices, however, remains a subject of interest. In this descriptive analysis, we assessed the most commonly reported adverse events (AEs) for a home-use IPL device from postmarketing surveillance and qualitatively compared these with AEs from clinical studies and medical device reports of home-use IPL treatments. For this analysis of voluntary reports, we queried a distributor's postmarketing database for IPL devices for the period beginning January 1, 2016, to December 31, 2021. All sources of comments, for example, phone, e-mail, company-sponsored web sites, were included in the analysis. AE data were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Also, we conducted a PubMed search to identify AE profiles from existing literature on home-use IPL devices and we searched the Manufacturer and User Facility Device Experience (MAUDE) database for reports on home-use IPL devices. These results were qualitatively compared to the data in the postmarketing surveillance database. A total of 1692 cases involving IPL were identified from voluntary reports of AEs between 2016 and 2021. The shipment-adjusted reporting rate for AE cases (number of AE cases/100,000 shipped IPL devices) was 67/100,000 during this 6-year period. The most commonly reported AEs were pain of skin 27.8% (470/1692), "thermal burn" 18.7% (316/1692), and erythema 16.0% (271/1692). Among the top 25 AEs reported, no unexpected health events were observed. The reported AEs were qualitatively similar to the pattern seen in clinical studies and the MAUDE database associated with such home-use IPL treatments. This is the first such report documenting AEs for home-use IPL hair removal from a postmarketing surveillance program. These data are supportive of the safety of such home-use low-fluence IPL technology.

Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database.

This research aims to explore and compare the signals of rhabdomyolysis from the use of Proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Rhabdomyolysis and related terms submitted between 2013 and 2021 were retrieved from the FAERS database. The data were analyzed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM) and the information component (IC). The signals of rhabdomyolysis associated with PPIs use were detected in both 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) utilizers and non-utilizers. A total of 7,963,090 reports were retrieved and analyzed. Fifty-seven reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association. The ROR was 2.5 (95% confidence interval [CI] 1.9-3.2) for PPIs in non-statin-included reports and 2 (95% CI: 1.5-2.6) for PPIs in statin-included reports. Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports compared to statin-included reports. Plain language summaryProton Pump Inhibitors and rhabdomyolysis risk Background: The FDA created the FDA Adverse Event Reporting System (FAERS) database to support post-marketing surveillance programs. The FAERS is a computerized database with more than nine million adverse event reports, including all reports from 1969 to the present. This research aims to explore and compare the signals of rhabdomyolysis from the use of proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Research design and methods: We retrieved rhabdomyolysis and related terms submitted between 2013 and 2021 from the FAERS database. Then, we analyzed the data that we found. We detected the signals of rhabdomyolysis associated with PPIs use in both statins utilizers and non-utilizers.Results: We retrieved and analyzed a total of 7,963,090 reports. We found 57 reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association.Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports than in statin-included reports.

Biologics for Inflammatory Bowel Disease in Clinical Practice: A Calabria (Southern Italy) Prospective Pharmacovigilance Study.

The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting. This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled. Overall, 358 patients with a diagnosis of active Crohn's disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; p = 0.47), GOL (7/37; p = 0.78), ADA (13/89; p = 0.18), and VDZ (3/17; p = 0.52), no AEs have been noticed with UST (0/1). Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs.

Real-world safety and effectiveness of canakinumab in patients with cryopyrin-associated periodic fever syndrome: a long-term observational study in Japan.

A post-marketing all-patient surveillance program was conducted to evaluate the safety and effectiveness of canakinumab, a monoclonal anti-interleukin-1β antibody, in patients in Japan with cryopyrin-associated periodic fever syndrome (CAPS), including familial cold auto-inflammatory syndrome, Muckle-Wells syndrome, and neonatal onset multisystem inflammatory disease. All patients with CAPS who received canakinumab treatment after drug approval in Japan were registered in this non-interventional, observational study. The observation period per patient was two years. Patients newly treated with canakinumab (New patients; NP) and those continuously treated with canakinumab following clinical trials (Roll-over patients; RP) were included. Data collection of clinical symptoms affecting physical function and prognosis was not mandated but assessed where available. Here, the interim results are reported. Of 87 patients in the safety set, the proportion of patients with any adverse drug reactions (ADRs) and any serious ADRs was 31.03% and 3.45%, respectively. The most common ADRs reported under system organ class were infections and infestations (20.69%). Of 84 patients in the effectiveness set, 75.76% and 83.33% of NP and RP, respectively, were responders at Week 24, achieving complete response without relapse. Responder rates were maintained up to Week 104. Clinical symptoms affecting physical function and prognosis remained unchanged in over half of those patients. Interim results provided the safety profile of canakinumab in a real-world setting, and identified no new safety concerns. Treatment with canakinumab has suggested sustained remission in the majority of patients in the real-world setting.

Top studies of 2021 relevant to primary care: From the PEER team.

To summarize 10 high-quality studies or guidelines from 2021 that have strong relevance to physicians in comprehensive family practice. Routine literature surveillance of abstracts in high-impact journals and EvidenceAlerts was completed by the PEER (Patients, Experience, Evidence, Research) team, a group of health care professionals with a research interest in evidence-based medicine and primary care. Abstracts were screened, selected, and ranked by the PEER team. The articles from 2021 that are most likely to impact primary care practice discuss the following topics: empagliflozin for heart failure with preserved ejection fraction; semaglutide for weight loss; stopping antidepressants in primary care; inhaled budesonide for COVID-19; acetylsalicylic acid for preeclampsia prevention; quarter-dose blood pressure medications for hypertension; aggressive blood pressure control for elderly patients; kangaroo care for low-birth-weight infants; footwear for knee osteoarthritis; and delayed antibiotics for pediatric respiratory infections. Two "honourable mention" studies are also briefly reviewed. Research from 2021 produced several high-quality studies in cardiovascular care but also addressed a variety of conditions relevant to primary care including weight loss, depression, and COVID-19.

Safety and effectiveness of Omnitrope® (somatropin) in PATRO Children: a multi-center, post-marketing surveillance study comparison of US and international cohort data

There are known geographical differences in growth hormone deficiency (GHD) patient populations and treatment practices. Here, we present a comparison of safety and effectiveness data from patients treated with recombinant human growth hormone (rhGH) in the USA versus other countries. PAtients TReated with Omnitrope® (PATRO) Children is an international, non-interventional study with Omnitrope® (somatropin, Sandoz Inc.). All visits and assessments are carried out according to routine clinical practice, and doses of Omnitrope® are given according to country-specific prescribing information. By September 2018, 294 patients had been enrolled in the USA (53% rhGH-naïve) and 6206 patients had been enrolled across 13 other countries (international group; 86% rhGH-naïve). The most common indication in both groups was GHD. Overall, 194 US patients (66%) and 2977 international patients (48%) experienced adverse events (AEs; 886 and 11,716 events, respectively), most of which were of mild or moderate intensity. The AEs were suspected to be treatment-related in five US patients (1.7%) and 452 international patients (7.3%). All reported neoplasms were benign, non-serious, and considered unrelated to rhGH therapy. No cases of diabetes mellitus or hyperglycemia were reported. In rhGH-naïve GHD patients, after 3 years of rhGH therapy, the improvement in mean height SD score from baseline was + 1.25 and + 1.35 in US and international patients, respectively.Conclusion: Omnitrope® treatment appears to be well tolerated and effective in US patients and those from other countries. Across the pediatric indications included, there was no evidence of an increased risk of developing uncommon or unexpected AEs with rhGH.Trial registration: NA.What is Known:• Continued monitoring of patients treated with recombinant human growth hormone (rhGH) is important, particularly in terms of diabetogenic potential and the risk of malignancies.• The PAtients TReated with Omnitrope® (PATRO) Children study is a long-term, post-marketing surveillance program for the rhGH Omnitrope®.What is New:• Omnitrope® is well tolerated and effective in US patients, and those from other countries.• Across all indications included, there were no unexpected adverse events and there was no evidence of an increased risk of developing malignancies or diabetes.

Postmarketing surveillance of adverse events following meningococcal B vaccination: data from Apulia Region, 2014–19

ABSTRACT Since the multicomponent meningococcal B vaccine introduction, the Apulian Regional Health Authority implemented postmarketing surveillance program, as provided by Italian laws. From National Pharmacovigilance Network, we selected 4CMenB AEFIs reported in Apulia from 01 January 2014 to 31 December 2019, while the number of 4 cMen B doses administered per year was obtained from the regional immunization database (GIAVA). For each subject who experienced an adverse event following meningococcal B vaccine (AEFIs), a predefined form was filled in. A total of 214 AEFIs (26.5 × 100.000 doses) were reported after any dose of MenB-4 c vaccination of which 58/214 (27.1%) were classified as serious (7.2 × 100,000 doses), 145/214 (67.8%) as not serious (180 × 100,000 doses), and 11/214 (5.1%) as undefined (1.3 × 100,000 doses). The average age of subjects who experimented and AEFI was 30 months. The majority of serious AEFIs were reported in 2- to 11-month-old children (44/57; 77.2%). A total of 31/58 (3.8 × 100,000 doses; 53.4%) serious AEFIs were reported as having a ‘consistent causal association’ with vaccination. Of these, fever/hyperpyrexia was reported in 21/31 (2.6 × 100,000 doses; 67.7%); hypotonic-hyporesponsive episode was reported in 7/31 (0.9 × 100,000 doses [add %-age]) and was the most frequent adverse event with neurological symptoms. A total of 13/31 (41.9%) serious AEFIs classified as ‘consistent causal association’ were reported after the first dose of 4cMenB, of these 5/13 (38.5%) children did not complete the vaccination schedule. Our data seemed to confirm, in a large population, the a good safety profile of the universal mass vaccination with 4CMENB.

Long-term safety and outcomes in hereditary tyrosinaemia type 1 with nitisinone treatment: a 15-year non-interventional, multicentre study

Since the EU approval of nitisinone in 2005, prognosis for patients with hereditary tyrosinaemia type 1 has changed dramatically, with patients living with the disease now reaching adulthood for the first time in history. This study aimed to assess the long-term safety and outcomes of nitisinone treatment in patients with hereditary tyrosinaemia type 1. We did a non-interventional, non-comparative, multicentre study in 77 sites across 17 countries in Europe and collected retrospective and prospective longitudinal data in patients with hereditary tyrosinaemia type 1 who were treated with oral nitisinone during the study period (Feb 21, 2005, to Sept 30, 2019). There were no specific exclusion criteria. Patients were followed-up with an investigator at least annually for as long as they were treated, or until the end of the study. The primary endpoints, occurrence of adverse events related to hepatic, renal, ophthalmic, haematological, or cognitive or developmental function, were assessed in the complete set (all patients already receiving treatment at the index date [Feb 21, 2005] or starting treatment thereafter) and the index set (the subset of patients who had their first dose on the index date or later only). 315 patients were enrolled during the study period (complete set). Additionally, data from 24 patients who had liver transplantation or died during the post-marketing surveillance programme were retrieved (extended analysis set; 339 patients). Median treatment duration was 11·2 years (range 0·7-28·4); cumulative nitisinone exposure was 3172·7 patient-years. Patients who were diagnosed by neonatal screening started nitisinone treatment at median age 0·8 months versus 8·5 months in those who presented clinically. Incidences of hepatic, renal, ophthalmic, haematological, or cognitive or developmental adverse events were low. Occurrence of liver transplantation or death was more frequent the later that treatment was initiated (none of 70 patients who started treatment at age <28 days vs 35 [13%] of 268 patients who started treatment at age ≥28 days). 279 (89%) of 315 patients were assessed as having either very good or good nitisinone treatment compliance. Treatment and diet compliance declined as patients aged. Suboptimal plasma phenylalanine and tyrosine levels were observed. The majority of patients were reported to have good overall clinical condition throughout treatment; 176 (87%) of 203 during the entire study, 98% following 1 year of treatment. Long-term nitisinone treatment was well tolerated and no new safety signals were revealed. Life-limiting hepatic disease appears to have been prevented by early treatment start. Neonatal screening was the most effective way of ensuring early treatment. Standardised monitoring of blood tyrosine, phenylalanine, and nitisinone levels has potential to guide individualised therapy. Swedish Orphan Biovitrum (Sobi).

Biosimilar trastuzumab active post marketing surveillance real world 2020 data update: Results from a patient support program for patients under treatment with the first biosimilar trastuzumab approved in Brazil.

e14504 Background: In 2017, biosimilar trastuzumab (Zedora) became the first biosimilar trastuzumab approved in Brazil. In May 2018 an active postmarketing surveillance program was instituted. Data from this program was presented in ASCO in 2019 and 2020. Now, with an extended follow up (May 2018 to December 2020) and more patients included, we present updated data from the surveillance program. Methods: This is a prospective observational study to evaluate data from the patient support program. Patients who received prescription for biosimilar trastuzumab were invited to participate. After agreement of informed consent, they were followed by periodical phone calls after each infusion and up to 3 months after the end of treatment. Treatment related data and adverse events (AEs) were collected. Results: A total of 74 reports containing 656 adverse events (AEs) were received from the active postmarketing surveillance program between May 2018 and December 2020. Of the 74 reports, 73 are female patients with HER2+ breast cancer (BC) and 1 is a male patient with gastric adenocarcinoma. The patients mean age was 52 years (31 to 79 years). Regarding to AEs severity and expectedness, 588 (89.63%) were non-serious AE (413 expected / 175 unexpected) and 68 (10.37%) were serious AE (51 expected / 17 unexpected). Considering all serious unexpected AEs (17), 13 were assessed as not related to trastuzumab therapy and 4 were assessed as related to therapy. For the 175 non-serious unexpected AEs, 56 were assessed as not related to therapy and 119 were assessed as related to therapy. The three most frequently reported AEs according to SOC (System Organ Classification) were general disorders and administration site conditions 111 (16.92%), gastrointestinal disorders 98 (14.93%) and nervous system disorders 88 (13.41%). The five most commonly reported adverse events (MedDRA PT - Preferred term) were diarrhea 27 (4.11%), fatigue 24 (3.66%), nausea 22 (3.35%), weight decreased 18 (2.74%) and infusion related reaction 17 (2.59%). Further monitoring is continued. Conclusions: Nature of AEs noted in patients with breast cancer and gastric cancer treated with biosimilar trastuzumab (Zedora) were consistent with the known safety profile of Trastuzumab. The risk benefit remains consistent with the reference safety information and no new safety signals were detected.[Table: see text]

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study.

Since the influenza season 2018/19, the Italian Ministry of Health recommended a dose of cell-based quadrivalent vaccine (Flucelvax Tetra) for HCWs (healthcare workers), because this vaccine seemed more efficacious in the prevention of AH3N2 virus. Due to the lack of pre-registration data, the safety profile of this new vaccine must be investigated in post-marketing surveillance. The aim of our study is to evaluate, through a post-marketing active surveillance program developed during the 2019/20 influenza season, any Adverse Events Following Immunization (AEFIs) that happened in the 7 days after immunization with Flucelvax Tetra. The study was carried out in a sample of HCWs of Policlinico General University-Hospital (Apulia, South Italy). AEFIs were classified as ‘serious’ or ‘not serious’ according to the WHO (World Health Organization) guidelines; the WHO causality assessment algorithm was applied to classify serious AEFIs. A total of 741 HCWs were enrolled, and 430 AEFIs (reporting rate: 58.0 (95%CI: 54.4–61.6) × 100 enrolled) were recorded. Of these, 429 of 430 (99.8%; reporting rate: 57.8 (95%CI: 54.2–61.5) × 100 enrolled) were classified as not serious and one (0.2%; reporting rate: 0.13 (0.03–0.75) × 100 enrolled) was classified as serious. Local reactions were the adverse reaction reported most frequently (88%); regarding the serious AEFI, causality assessment excluded the causal link with the administration of the vaccine. All the AEFIs resolved without sequelae. Flucelvax Tetra showed a profile of high safety. Due to their characteristics of greater sensitivity than passive surveillance, active surveillance programs can be useful in defining the safety profiles of a given vaccine/drug in certain population subgroups.

Knowledge, Attitudes and Practices Survey of Medication Safety among Community Pharmacists in Aden-Yemen

Introduction: All health professionals' participation is essential for ensuring quality and successful national post-marketing surveillance programs. This study aimed to assess the knowledge, attitudes, and practices (KAP) among Yemeni community pharmacists (CPs) regarding medication safety in a poor-resource setting.&#x0D; Methods: A survey was conducted among CPs in Aden governorate. The tool comprised of demographic profile, knowledge, attitude, and practice aspects of medication safety. The survey also studied the opinion about the future and benefits of Adverse Drug Reaction (ADR) reporting in Yemen. The data collected was analyzed using descriptive statistics such as frequencies, percentages, and means (SD).&#x0D; Results: A total of 450 CPs were enrolled in the study. Most of the participants were males (75%) with a bachelor's degree (91.9%) and between 3-6 years of experience (28%). The majority of CPs had good knowledge regarding the perception and objectives of Pharmacovigilance (PV) and ADRs. Approximately 41% of participants knew the purpose of PV as an essential system for public health and safety concerning drug use. Additionally, the Yemeni pharmacists had a positive attitude towards the reporting system. Approximately 84% of responders admitted that PV is the responsibility of the pharmacists. The majority of the participants (80%) declared no reporting form available at their workplace. According to CPs, 59% said that relevant authorities do not widely promote ADR reporting in Yemen, and 57% replied that the patient's lack of information is an obstacle in the reporting system. Approximately 89% of the CPs believed that reporting ADRs would improve patient safety.&#x0D; Conclusions: The CPs have a positive attitude towards PV and an acceptable degree of knowledge. However, the practice level should be upraised.

Risks of Skin, Hair, and Nail Supplements.

Skin, hair, and nail supplements, sometimes referred to as "beauty supplements" or "ingestible skin care," are a large and growing industry. These products may contain vitamins and minerals, sometimes in very high doses. They may also contain herbs, hormones, microbes, or animal derivatives such as fish oils and collagen powders. Dietary supplements are regulated as foods, not as drugs, by the US Food and Drug Administration (FDA). Therefore, manufacturers do not need to provide any proof of safety, efficacy, or quality prior to sale. This is of serious concern, as many adverse effects due to supplement components have been reported. The potential risks cover multiple categories. These include acute toxicities, such as choking, as well as chronic toxicities, such as increased risk of diabetes. Teratogenicity and interactions with drugs and laboratory testing have been documented in research studies. Other risks include potentially increased risk of cancer with long-term use, allergic reactions, and others. It is vital that physicians educate their patients on these risks. As no post-marketing surveillance programs are required for supplements, our understanding of supplement risks is incomplete. Physicians should be wary of these risks and encourage further research and regulation.

Safety and Efficacy of Melatonin in Chronic Tension-Type Headache: A Post-Marketing Real-World Surveillance Program.

IntroductionTension-type headache (TTH) is the most prevalent primary headache. Every year, about 2–3% of patients with TTH progress to chronic TTH with daily or near-daily headache, warranting preventive treatment. The treatment of chronic TTH is complex and very often associated with significant tolerability issues. To date, melatonin has been studied in only a few small uncontrolled trials. The aim of this surveillance program was to evaluate the efficacy of melatonin (Melaxen®) in patients with TTH and disruption of circadian rhythms in real-world practice.MethodsSixty-one patients with chronic TTH were enrolled. After the 30-day baseline period, patients took 3 mg of melatonin at bedtime for 30 days with a follow-up period of another 30 days. VAS pain intensity assessments, Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), HIT-6 and Levin sleep quality scores were obtained at the baseline visit, at month 1, and month 2.ResultsA significant decrease in the number of headache days per month, VAS pain intensity, HAM-A, HAM-D and HIT-6 scores, and an improvement in sleep quality were observed throughout the study. No treatment-emergent adverse events were reported.ConclusionsMelatonin is an effective and safe alternative for the treatment of chronic TTH.

Postmarketing Safety of Vaccines Approved by the U.S. Food and Drug Administration

Vaccines are one of the greatest achievements in public health. Prevalence and clinical significance of emerging postapproval, vaccine-related safety issues have not been systematically studied. To explore postmarketing safety modifications in U.S. Food and Drug Administration (FDA)-approved vaccine labels. Retrospective cohort study. United States. Initial and subsequent labels of all vaccines that were FDA-approved between 1 January 1996 and 31 December 2015. The primary aim was a descriptive analysis of the prevalence and characteristics of postapproval, safety-related label changes. The secondary aim was to describe the distribution of data sources triggering these modifications. The study cohort comprised 57 FDA-approved vaccines. Initial approval for 53 (93%) of the vaccines was supported by randomized controlled trials, with a median cohort size of 4161 participants (interquartile range, 2204 to 8634 participants). There were 58 postapproval, safety-related label modifications associated with 25 vaccines (49 warnings and precautions, 8 contraindications, and 1 safety-related withdrawal). The initial approval trial characteristics were similar in vaccines with and without postmarketing, safety-related label modifications. The most common safety issue triggering label modifications was expansion of population restrictions (n = 21 [36%]), followed by allergies (n = 13 [22%]). The most common source of safety data was postmarketing surveillance (n = 28 of 58 [48%]). The data source of the initial signal triggering safety-related label changes may not necessarily represent all safety data received and processed by the FDA. Over a 20-year period, vaccines were found to be remarkably safe. A large proportion of safety issues were identified through existing postmarketing surveillance programs and were of limited clinical significance. These findings confirm the robustness of the vaccine approval system and postmarketing surveillance. None.

Biosimilar trastuzumab active post-marketing surveillance real-world data update: Results from a patient support program for patients under treatment with the first biosimilar trastuzumab approved in Brazil.

e15626 Background: In 2017, biosimilar trastuzumab (Zedora) became the first biosimilar trastuzumab approved in Brazil. In 2019, biosimilar trastuzumab early data from an active postmarketing surveillance program were presented in ASCO. Now, with an extended follow up and more patients included, we present updated data from the surveillance program. Methods: This is a prospective observational study based on a patient support program. HER2 + breast cancer (BC) who received prescription for biosimilar trastuzumab were invited to participate. After agreement of informed consent, they were followed by periodical phone calls after each infusion and up to 3 months after the end of treatment. Treatment related data and adverse events (AEs) were collected. Results: A total of 76 female patients with HER2 + BC were enrolled in the program between May 2018 and December 2019. 74 patients with median age 51 (range 30 to 80) received at least one biosimilar trastuzumab infusion. Out of these, 52 (70.3%) patients reported 385 AEs all-causality (Table 1). Regarding severity and expectedness, 344 (89.4%) were non-serious AE (243 expected / 101 unexpected) and 41 (10.6%) were serious AE (29 expected / 12 unexpected). Considering all serious unexpected AEs (12), 8 were assessed as unlikely and 4 as likely. For the non-serious unexpected AEs (101) causality assessment was unlikely in 32 AEs, likely in 68 AEs and conditional in 1 AE. The three most frequently reported AEs according to SOC (System Organ Classification) were gastrointestinal disorders 59 (15.3%), general disorders and administration site conditions 57 (14.8%). The five most reported symptoms (PT - Preferential Term) were nausea 15 (3.9%), fatigue 14 (3.6%), infusion reactions 14 (3.6%), diarrhea 9 (2.3%) and insomnia 9 (2.3%). Further monitoring is continued. Conclusions: Nature of AEs for biosimilar trastuzumab are consistent with the label in female patients with HER2 + BC. The risk benefit remains consistent with the label and no new safety signals were detected. [Table: see text]