Common Adverse Drug Reactions Research Articles

Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients. As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients. A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature. In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India. In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR's and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists' training in rural locations.

Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs. Among 1430 patients receiving anti-TB therapy, 440 (30.77%) patients showed at least 1 ADR induced by anti-TB drugs. Hyperuricemia was the most common ADR, followed by hepatic function test abnormality, liver damage and gastrointestinal reactions. Significant differences (P < .05) were also seen in diabetes, age, treatment duration, type of TB (extrapulmonary) and some therapeutic regimens between ADR group and non-ADR group, respectively. Multivariate logistic regression analysis showed that treatment duration (OR = 1.029, 95%CI[1.018-1.040], P = .000), type of TB (extrapulmonary, OR = 1.487, 95%CI[1.134-1.952], P = .004) and some therapeutic regimens (HREZ, OR = 1.425, 95%CI[0.922-2.903], P = .001; HRZS, OR = 2.063, 95% CI[1.234-3.449], P = .006; HRZ, OR = 3.623, 95%CI[2.289-5.736], P = .000) were risk factors for ADRs induced by anti-TB drugs. Anti-TB drugs usually induced the occurrence of severe and frequent adverse effects, such as hyperuricemia. Treatment duration, HREZ, HRZS and HRZ regimens, and type of TB (extrapulmonary) should be considered as high-risk factors. Thus, it should be recommended to consider optimum management during anti-TB therapy, particularly hyperuricemia monitoring and hepatic function test.

Post-marketing surveillance of quetiapine fumarate extended-release tablets in patients with bipolar depression.

This study aimed to verify the real-world efficacy and safety of quetiapine fumarate extended-release tablets (Bipresso® 50 mg and 150 mg; marketing authorization holder is KYOWA Pharmaceutical Industry Co., Ltd., Osaka, Japan) in patients with bipolar depression. We performed a post-marketing surveillance with an observation period of 12 weeks. In the safety analysis group (n = 345), adverse drug reactions (ADRs) occurred in 111 patients (32.17%). The most common ADRs (>1%) were somnolence in 55 patients (15.94%), akathisia in 11 (3.19%), dizziness in 10 (2.90%), weight increase in 6 (1.74%), thirst in 5 (1.45%), and hypersomnia, constipation, and nausea in 4 patients each (1.16%). The only severe ADR was one patient of suicidal ideation, and "longer time since the onset of the first episode" (p = 0.011) and "presence of complications" (p < 0.001) were identified as significant risk factors for the occurrence of ADRs. In the efficacy analysis group (n = 265), the average changes from baseline in the total Montgomery-Åsberg Depression Rating Scale (MADRS) score were -7.3 ± 8.8, -12.2 ± 10.7, -16.8 ± 12.7, and -13.2 ± 12.7 points after 4, 8, and 12 weeks, and at the last evaluation, respectively. The mean MADRS total score decrease had no significant association with maximum daily dose, diagnosis, and presence or absence of prior or concomitant treatment for bipolar disorder with mood stabilizers/antipsychotics/antidepressants. The efficacy of quetiapine fumarate extended-release tablets was confirmed in clinical practice, and no new safety concerns or risks were identified.

Analysing adverse drug reaction patterns observed during district residency program: a prospective observational study

Background: Adverse drug reactions (ADRs) pose a substantial cost to global healthcare systems. The heterogeneous patient demographics and healthcare environments of district residency programmes (DRPs) provide special possibilities for detecting trends of ADRs. In order recognize recurring trends and related variables, this study will examine ADR incidents that occur during DRPs. Methods: A prospective observational research with forty-three patients was carried out. Standardized reporting forms were used to gather data on ADRs, and descriptive statistical techniques were used to analyse the results. We evaluated medication information, patient demographics, and ADR features to seek for patterns and potential causes. Results: Preliminary analysis revealed a diverse range of ADRs observed during DRPs, spanning various severity levels and therapeutic classes. Common ADRs included gastrointestinal disturbances, allergic reactions, and central nervous system effects. Factors such as patient age, polypharmacy, and comorbidities emerged as potential predictors of ADR occurrence. Conclusions: The panorama of ADRs seen during DRPs is clarified by this study, underscoring the significance of careful monitoring, and reporting mechanisms in these initiatives. Gaining insight into ADR trends and related variables can help in improving patient safety, simplifying drug management plans, and directing future educational initiatives for medical professionals.

Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 μg in Japanese men with nocturia due to nocturnal polyuria. Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 μg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

Abstract CT193: Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity of AST-021p, a novel cancer vaccine targeting HSP90-derived epitopes in advanced solid tumor patients (CornerStone-002)

Abstract Background: AST-021p is an "off-the-shelf" therapeutic cancer vaccine composed of two peptides, AST-021p4 and AST-021p5, derived from MHC class II-specific epitopes of Hunam HSP90 protein. Both peptides serve as antigenic determinants for HSP90 and act as a tumor-associated antigen (TAA) inducing activation of type 1 helper T cells (Th1). Th1 cell immunologically elicited by AST-021p secrete cytokines, including IFN-γ, and activate local antigen presenting cells (APC) enhancing cross priming at the tumor site. This immunological activity, through the mechanism of cross priming, sequentially leads to the activation of cytotoxic T cells and epitope spreading. In preclinical studies using the MMTV neu gene overexpressing mouse model, the administration of the HSP90 peptide vaccine, AST-021p, significantly inhibited tumor growth. Based on these scientific rationales, The first-in-human (FIH) study was conducted to evaluate the safety, tolerability, and immunogenicity of AST-021p in advanced solid tumor patients have no treatment option. Methods: Phase 1 study (CornerStone-002, NCT No.: 04864418) was conducted on patients with recurrent or metastatic solid tumors for whom applicable standard treatment options were unavailable (patient enrollment period: June 9, 2021, to June 14, 2023). Four-dose cohorts of AST-021p (Cohort 1: 1.2mg, Cohort 2: 2.4mg, Cohort 3: 3.6mg, Cohort 4: 4.8mg) received three vaccinations at 2-week intervals (Priming immunization) followed by boosting immunization with 4-week interval based on PI's discretion. Enrolling one patient initially in the lowest dose cohort, Cohort 1 (1.2mg), dose escalation occurred sequentially after confirming safety and tolerability. Subsequently, each dose cohort (Cohort 2: 2.4mg, Cohort 3: 3.6mg, Cohort 4: 4.8mg) enrolled six patients each for vaccination. Antigen-specific immune response was assessed by IFNγ ELISPOT using PBMCs from the subjects at baseline, 4 weeks, and 8 weeks. Results: During the study period, a total of 22 patients were enrolled (Cohort 1: 1, Cohort 2: 6, Cohort 3: 8, Cohort 4: 7). The median age of the patients was 66, with a gender distribution of 14 males and 8 females. Among the 22 patients, 20 completed the priming immunization with 3 vaccinations, and 7 of them proceeded with the boosting immunization. A total of 75 adverse events were reported in 21 patients (95.5%). Adverse drug reactions (ADRs) occurred in 15 patients (68.2%), accounting for 92 cases. The most common ADR was injection site reaction (ISR), observed in 15 patients (68.2%), with 35 cases and all reactions were graded as 1 or 2. Serious adverse events (SAEs), including gastrointestinal hemorrhage, vomiting, and aspiration, were observed in 3 patients (13.6%), totaling 3 cases. However, these events were unrelated to AST-021p. Conclusions: This study, as the first-in-human (FIH) administration of the AST-021p, demonstrated safety and tolerability across all four dose groups. Plus, optimal immunogenic dose (OID) and recommended phase 2 dose (RP2D) were confirmed based on AST-021p-specific immunogenicity and safety. Citation Format: Eun Joo Kang, Kyoungmin Lee, In Ho Kim, Ju Won Kim, Jwa Hoon Kim, Soohyeon Lee, Jiwon Lee, Kabsoo Shin, Sejun Park, Joori Kim, Hyun Won Shin, Kyong Hwa Park. Phase 1 clinical trial evaluating the safety, tolerability, and immunogenicity of AST-021p, a novel cancer vaccine targeting HSP90-derived epitopes in advanced solid tumor patients (CornerStone-002) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT193.

Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2years were treated with Denosumab, 42% with 120mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70mg. To avoid ADRs 500mg of calcium and 400IU of vitamin D orally were used. Initial effective response was reported after 1-3months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120mg, 60 or 70mg in patients < 45 or 50kg for ≥ 12months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

Adverse Drug Reactions at Primary Health Centres in Malaysia

Background: Adverse drug reactions can lead to a substantial economic burden on patients and the country. This study aims to analyze the pattern of adverse drug reactions and assess the causality of the adverse events and severity of adverse drug reactions in primary health centers in Malaysia. Methodology: This retrospective study used case series analysis and data from six Malaysian primary health centers. The patients were analyzed for gender, age, class of drugs involved, organ system involved in the adverse reaction, severity using Hartwig’s severity assessment scale and causality using the Naranjo ADR probability scale. Data were analyzed using descriptive statistics. Results: In 113 adverse drug reactions were reported. Cardiovascular drugs commonly caused adverse drug reaction (38%), followed by anti-infective agents (20%), skin and subcutaneous disorders were the common adverse drug reactions encountered (23%). The severity of the adverse reaction was level 2 in most patients (69. 9%). Adverse drug reaction was mostly found to be probable (48.7%), and 64% of the patients recovered from the adverse drug reaction. Conclusion: Cardiovascular drugs commonly cause adverse drug reactions. Level 2 and mild reactions were widely observed. The causality assessment was probable in most of the patients.

Abstract 1965: 3HP-2827-high selective inhibitor of FGFR2, a best-in-class therapy for FGFR2-driven solid tumors

Abstract FDA-approved pan-FGFR inhibitors bring encouraging results in solid tumors. However, resistance mechanisms and side effect profiles may limit their clinical utility. We designed 3HP-2827, a highly selective and potent small molecule inhibitor of FGFR2, to treat solid tumors harboring FGFR2 alterations, including amplifications, mutations, and fusions to overcome these limitations. 3HP-2827 inhibits FGFR2 enzyme activity with more than 1623-fold selectivity over FGFR1 and FGFR3. 3HP-2827 inhibits cell proliferation with IC50 &amp;lt;10 nM and 30 nM in FGFR2 amplified and FGFR2-mutant cancer cell lines, respectively. 3HP-2827 demonstrates high kinome selectivity for FGFR2 against a panel of 485 human kinases, resulting in 90.1% inhibition of FGFR2, and no other kinases showed greater than 75% inhibition. 3HP-2827 leads only modest activity at 10 µM against PDE4D2 and LCK in 44 distinct common adverse drug reaction targets, supporting its high degree of safety. 3HP-2827 also demonstrates a dose-dependent inhibition of phosphorylation of FGFR2 and FGFR2 signaling pathway nodes, including ERK and AKT, in the FGFR2-dependent cancer cell line. In vivo, 3HP-2827 demonstrates potent antitumor activity in cell- and patient-derived xenograft mouse models, including FGFR2-amplified gastric cancer, FGFR2-mutant (N549K) endometrial cancer, FGFR2 fusion ICC and gastric cancers. Strikingly, 3HP-2827 demonstrates superior activity in patient-derived ICC and gastric cancer, cell-derived endometrial cancer (CDX) in tumor and pFGFR2 inhibitions. In the ICC PDX model, 3HP-2827 also induces the regression of pemigatinib-resistant tumors. 3HP-2827 is well tolerated in the toxicology studies, and no hyperphosphatemia or tissue mineralization is observed at 150 mg/kg/kg/day in rats and 120 mg/kg/day in dogs. The data support that 3HP-2827, a potential to be a best-in-class selective FGFR2 inhibitor, will be studying clinically at the beginning of 2024. Citation Format: Susan S. Liu-Chen, Jufang Lin, Jingyu Hu, Yanchao Liu, Weibo Zhang, Zhixiong Zhang, Yan Ding, Jinqiu Liu, Kevin Chen, Shaojing Hu. 3HP-2827-high selective inhibitor of FGFR2, a best-in-class therapy for FGFR2-driven solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1965.

Adverse Drug Reactions and Prescription Patterns of Antiretroviral Drugs: A Longitudinal Observational Study From a Tertiary Care Hospital in Western India.

Background In 2018, the World Health Organisation (WHO) released interim guidelines, advising a change of regimens to dolutegravir-based first- and second-line antiretroviral therapy (ART), based on which, in 2021, the National Aids Control Organisation (NACO) updated its guidelines to include the tenofovir+ lamivudine + dolutegravir (TLD) regimen as a first line of therapy for all people living with HIV (PLHIV) and second- and third-line regimens to dolutegravir-based regimens. Considering this change of regimen, the adverse drug reaction (ADR) profiling and longitudinal prescription pattern of antiretroviral and concomitant medications in adult patients at the ART centre of a tertiary care hospital were assessed in this study. Methods Ninety-seven PLHIV out of all the patients who attended the ART centre from September 2021 to July 2022 were enrolled and followed up for six months. The ADRs that occurred during this period were collected along with details of prescription patterns and analyzed by descriptive statistics. Causality assessment for ADR was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Results Seventy-eight percent (n=76 out of 97) of patients experienced at least one ADR, and 128 ADRs were seen in 97 patients. The most common ADRs were increased alkaline phosphatase (39.0%, n=128), dyslipidaemia (12.5%, n=128), and nephrotoxicity (10.1%, n=128). The drug most suspected of causing ADRs was dolutegravir (27.5%, n=342). The most common therapeutic regimen was TLD (71.2%, n=97). The most prescribed drug was lamivudine (30.6%, n=1183). The most prescribed concomitant medication was cotrimoxazole (15%, n=312). Conclusions Dolutegravir-based regimens have been implemented for PLHIV in a phased-out manner from previous non-dolutegravir-based ART regimens, which is in line with the recent NACO guidelines. However, it has also led to an increase in dolutegravir-associated ADRs like increased alkaline phosphatase, dyslipidaemia, and nephrotoxicity. Continuous monitoring of prescriptions and ADRs can add to our knowledge regarding their use and ADRs.

THE ADVERSE DRUG REACTIONS OF INTERMITTENT AND DAILY REGIMENS IN THE TREATMENT OF THE INTENSIVE PHASE OF TUBERCULOSIS

Objective: To study the adverse drug reactions (ADRs) of intermittent and daily anti-tubercular therapy in intensive phase (IP), in patients attending the RNTCP unit, Government Medical College (GMC), Thrissur. Methods: A prospective observational study was done at the RNTCP unit, GMC, Thrissur, during October 2016-2017. Two hundred and thirty-five patients satisfying inclusion criteria, receiving anti-tubercular therapy as intermittent and daily regimens were selected. Demographic data, risk factors, comorbidities, and investigations were recorded and patients were followed up for IP. Results of investigations, treatment outcome, and ADRs recorded after IP. ADRs were monitored and its causality and severity were assessed. Data were entered in MS Excel and analyzed using SPSS. Qualitative variables are represented as proportions and quantitative as mean and standard deviation. Associations were analyzed using appropriate statistical tests. Analysis was performed using paired t-test p&lt;0.05 taken as significant. Results: Orange-red urine and secretions were the most common ADR, followed by nausea, fatigue, heartburn, etc. Significant increase in random blood sugar, renal function tests (RFTs), and liver function tests (LFT) after treatment, then before noticed. 84.4% of patients from the daily group and 78% of patients from the intermittent group experienced ADRs. Causality was assessed using Naranjo’s algorithm and severity using a modified Hartwig and Siegel scale. Conclusion: The majority of patients developed ADRs, which were mild and managed symptomatically. Some reactions required alteration of therapy, reduction of drug dose, or change of suspected drug. To conclude, meticulous monitoring of ADRs in patients on anti-tubercular drugs is mandatory.

Long-term intraocular pressure-lowering efficacy and safety of ripasudil-brimonidine fixed-dose combination for glaucoma and ocular hypertension: a multicentre, open-label, phase 3 study.

To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT). This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (β-blocker) (Cohort 2); PG analogue, β-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout. In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity. These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT. Japan Registry of Clinical Trials Identifier: jRCT2080225063. 17 February 2020.

Sequence Labelling with 2 Level Segregation (SL2LS): A framework to extract COVID-19 vaccine adverse drug reactions from Twitter data

Social media data is an opportunistic resource for post-marketing surveillance of COVID-19 (Coronavirus disease of 2019) vaccines. However, the usage of the term Adverse Drug Reaction (ADR) in different contexts, which do not refer to adverse reactions to given vaccines, poses a great challenge for existing ADR extraction techniques. In the present work, a framework titled “Sequence Labelling with 2 Level Segregation” (SL2LS) has been proposed to extract adverse reactions of COVID-19 vaccines from Twitter data. It handles the mentioned challenge by deploying a Bidirectional Long Short-Term Memory (Bi-LSTM) based two-level classification model to segregate the tweets containing ADR terms that represent adverse reactions of vaccines from the tweets that comprise ADR terms which are not referring to adverse reactions of vaccines based on the context of ADR term usage and then employ domain-specific pre-trained Bidirectional Encoder Representations from Transformers for Biomedical Text Mining (BioBERT) sequence labelling model for extracting vaccine linked ADRs from segregated tweets. The proposed framework has been applied to Covaxin and Covishield COVID-19 vaccine data collected from Twitter and annotated with the help of a domain expert. It achieved the highest precision, recall and F1-score of 95.46%, 93.2% and 94.33%, respectively, in comparison to other state-of-the-art techniques. The validation of detected top 20 frequent ADRs of the two vaccines with official surveillance reports resulted in 19 verified ADRs for Covaxin and all 20 verified ADRs for Covishield and one unverified ADR “Blood Clot” for Covaxin which is a valuable lead for medical experts for further exploration. Further analysis shows that the two vaccines share some common ADRs viz. “Discomfort”, “Fever”, “Pain”, “Headache” and “Fatigue” and “Discomfort” and “Fever” are the most frequent ADRs associated with Covaxin and Covishield vaccines, respectively.

Post-marketing surveillance of zinc acetate dihydrate for hypozincemia in Japan.

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 μg/dL to >90 μg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

Comparative analysis of newer classes of antidiabetics and the concept of pharmaceutical care – dealing with therapeutic problems

The prevalence of obesity is increasing rapidly. The latest World Health Organization – WHO report declares the disease as an epidemic. After pharmacodynamic, pharmacokinetic, clinical and pharmacoepidemiologic data analysis and comparison of the three classes of antidiabetic medicinal products: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT2 inhibitors, a literature review of the topic, patient education and the concept of pharmaceutical care emerged as methods for dealing with the most common adverse drug reactions, safety concerns, and drug interactions.

Quantitative Signal Detection for COVID-19 Medicinal Products Based on Retrospective Analysis of Spontaneous Reports from the Russian Pharmacovigilance Database

SCIENTIFIC RELEVANCE. The pandemic of novel coronavirus infection (COVID-19) led to a drastic increase in the use of medicinal products of various therapeutic groups and increased spontaneous reporting of adverse drug reactions (ADRs). Therefore, it is necessary to analyse the reported information to identify potential safety signals.AIM. This study aimed at systematisation and quantitative analysis of data on the safety of COVID-19 medicinal products from the Russian pharmacovigilance database.MATERIALS AND METHODS. This retrospective analysis included spontaneous ADR reports submitted to the Russian pharmacovigilance database from 1 January 2020 to 31 December 2022. The authors applied disproportionality analysis to generate safety signals.RESULTS. During the stated period, the database website published 873 spontaneous reports on 1,636 ADRs associated with COVID-19 treatment. Most ADRs were associated with favipiravir (493 reports), hydroxychloroquine (87 reports), and olokizumab (85 reports). The most common ADRs included 273 (16.7%) abnormal investigation results, 203 (12.4%) hepatobiliary disorders, and 191 (11.6%) gastrointestinal disorders. The majority of adverse events, 674 (77%) cases, had favourable outcomes. Using frequency-based disproportionality analysis, the authors identified 23 potential safety signals based on disproportionately reported ADRs for azithromycin, dexamethasone, levilimab, lopinavir+ritonavir, molnupiravir, olokizumab, tofacitinib, tocilizumab, umifenovir, and favipiravir.CONCLUSIONS. The new safety signals require additional assessment of ADR reporting forms for causal relationship analysis, validation, prioritisation, and clinical interpretation. The frequency-based method did not identify safety signals for hydroxychloroquine, remdesivir, baricitinib, sarilumab, and anti-COVID-19 human immunoglobulin, but this does not rule out the possibility of detecting new causal relationships.

Evaluation of Apatinib-Related Hypertension and Identification of Clinical Risk Factors

Purpose. Hypertension (HTN) is one of the most common adverse drug reactions to tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF), but little is known about its clinical risk factors. The aim of this study was to elucidate the association between baseline clinical characteristics and the occurrence of HTN in advanced gastric cancer (GC) patients prescribed apatinib, a commonly used VEGF-TKI in China, in a real-world setting. Patients and Methods. Fifty-five GC patients treated with apatinib from December 1st, 2016, to December 1st, 2020, were retrospectively included in electronic medical records. Adverse drug reactions were defined according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariable logistic regression analyses were used to investigate potential clinical risk factors for apatinib-related HTN. Results. The incidence of apatinib-related HTN of all grades was 45.45%, and grade 3 HTN occurred in 16.36% of patients. The median maximal systolic blood pressure (SBP) during apatinib treatment was 153 mm·Hg, and the median time to event was 25 days. New-onset HTN occurred in 10/33 (30.30%) patients. Preexisting HTN (odds ratio [OR]: 4.155; 95% confidence interval [CI]: 1.252, 13.787; p=0.020) was the key independent risk factor associated with apatinib-related HTN. Conclusion. The incidence of HTN was high in patients treated with apatinib, and preexisting HTN was an independent risk factor. It is important to provide thorough and close monitoring of patients during treatment with apatinib, especially for those with preexisting HTN. This trial is registered with ChiCTR1900024531.

A retrospective and observational study of the adverse drug reactions reported in a tertiary care hospital

Background: Adverse drug reaction (ADR) is considered a common cause of prolonged hospitalization and death among patients. Pharmacovigilance is essential in the surveillance of adverse drug reactions. The responsibility of a healthcare professional is to report any adverse reaction that occurs with the use of drugs. This helps in providing a database and improving the safety of patients. The aim of the study was to determine the incidence of ADR, assess causality, severity, and preventability of the submitted adverse drug reactions, increase the awareness of preventability of adverse drug reactions in health care professionals by conducting regular workshops on ADR, and document occurrence of a rare ADR. Methods: A retrospective observational study was conducted to assess the ADR reported to the ADR monitoring Centre, for the past 6 years included in the study. The data were entered into Microsoft excel and analyzed using descriptive statistics. Mean and standard deviation were calculated for the categorical data. Drugs were classified according to the class. Reactions were analyzed using scales and presented in descriptive statistics. Results: A total of 95 ADR reports were received and reported. These ADRs were associated with a total of 108 drugs that were prescribed- the occurrence of ADRs dominated among females 60% (57). Antimicrobials were causing the highest number of adverse reactions 21 (19.44%) and antituberculosis drugs and radiocontrast media were associated with the following larger number of the ADRs 19 (17.59%). Intravenous at 40% was the most common route related to the development of ADR. The most common ADR caused by antimicrobials was rash (9), antitubercular therapy commonly caused hepatitis, and chills and rigors were more common with radiocontrast media. Most of the reactions observed in the patients were moderate reactions at 52.63% with 3.16% fatal ones. Conclusions: In this study, the predominant causative drugs associated with ADR were antimicrobials, antitubercular drugs, and radiocontrast media. The number of ADRs reported though was less there was a wide range of drugs causing ADR that were reported which gave a broader spectrum for analysis. There is a requirement for active monitoring of ADRs to understand the occurrence as well as help in prevention.

Enhancing antidepressant safety surveillance: comparative analysis of adverse drug reaction signals in spontaneous reporting and healthcare claims databases.

Background/Objective: Spontaneous reporting systems (SRS) such as the Korea Adverse Event Reporting System (KAERS) are limited in their ability to detect adverse drug reaction (ADR) signals due to their limited data on drug use. Conversely, the national health insurance claim (NHIC) data include drug use information for all qualifying residents. This study aimed to compare ADR signal profiles for antidepressants between KAERS and NHIC, evaluating the extent to which detected signals belong to common ADRs and labeling information. Materials and Methods: ADR signal detection in KAERS and NHIC databases, spanning January to December 2017, employed disproportionality analysis. Signal classes were determined based on System Organ Class (SOC) of the Medical Dictionary for Regulatory Activities (MedDRA). Also, Common ADR Coverage (CAC), the proportion of detected signals deemed common ADRs, and labeling information coverage (LIC) represented by mean average precision (mAP) were calculated. Additionally, protopathic bias and relative risk (RR) evaluation were performed to check for signal robustness. Results: Signal detection revealed 51 and 62 signals in KAERS and NHIC databases, respectively. Both systems predominantly captured signals related to nervous system disorders, comprising 33.3% (N = 17) in KAERS and 50.8% (N = 31) in NHIC. Regarding the type of antidepressants, KAERS predominantly reported signals associated with tricyclic antidepressants (TCAs) (N = 21, 41.2%), while NHIC produced most signals linked to selective serotonin reuptake inhibitors (SSRIs) (N = 22, 35.5%). KAERS exhibited higher CAC (68.63% vs. 29.03%) than NHIC. LIC was also higher in KAERS than in NHIC (mAP for EB05: 1.00 vs. 0.983); i.e., NHIC identified 5 signals not documented in drug labeling information, while KAERS found none. Among the unlabeled signals, one (Duloxetine-Myelopathy) was from protopathic bias, and two (duloxetine-myelopathy and tianeptine-osteomalacia) were statistically significant in RR. Conclusion: NHIC exhibited greater capability in detecting ADR signals associated with antidepressant use, encompassing unlabeled ADR signals, compared to KAERS. NHIC also demonstrated greater potential for identifying less common ADRs. Further investigation is needed for signals detected exclusively in NHIC but not covered by labeling information. This study underscores the value of integrating different sources of data, offering substantial regulatory insights and enriching the scope of pharmacovigilance.

Pattern of central nervous system related adverse drug reactions (ADRs) due to anti-retroviral therapy in HIV infected patients in tertiary care hospitals in North India

Background: Anti-retroviral therapy is associated with myriads of side-effects. Central nervous system related side effects are troublesome and mostly self limiting. Working knowledge of these side effects can improve the prescription habits of physicians. The study aimed pattern of central system related adverse drug reactions (ADRs) due to anti-retroviral therapy in HIV infected patients in tertiary care hospitals in North India. Materials and methods: A prospective observational study was conducted and all HIV positive patients, previously registered and new; attending OPD who encountered ADRs were enrolled in our study irrespective of their age and sex. Data was collected using ADR reporting form issued by Indian Pharmacopoeia Commission. Causality assessment was done by using Naranjo’s Probability Scale. Modified Hartwig severity scale was used to evaluate severity, WHO criteria for seriousness and guidelines of council for international organizations of medical sciences to decide the predictability of ADRs. Results: A total of 250 patients encountered various types of ADRs during the study period. Total number of ADRs recorded was 452. Out of total ADRs (n=452) recorded, 20.35% (n=92) were central system related ADRs. Most common central nervous system related ADR was dizziness. Most central nervous system related ADRs were of moderate type and possible in nature on causality assessment. Conclusion: Relatively overweight, older age and baseline CD4 absolute count below 250 cells/mm3, were predictors for central nervous system related side effects due to anti-retroviral therapy in HIV patients. We suggest that more stringent evaluation and monitoring should be carefully done in all HIV/AIDS patients who will receive and on efavirenz based anti-retroviral therapy, especially if they have the above predictors.