Common Adverse Drug Reactions Research Articles

Adverse Drug Reactions: A Retrospective Analysis from the ADR Monitoring Centre at a Tertiary Care Hospital

Background: Adverse Drug Reactions (ADRs) present significant challenges in healthcare, necessitating vigilant monitoring and analysis to enhance medication safety protocols. This retrospective study aimed to analyse ADRs reported at an Adverse Drug Reactions Monitoring Centre (AMC) to understand prevalence, patterns, and characteristics of ADRs. Methods: Retrospective data from January to December 2023 were collected from the AMC at Vaishampayan Memorial Medical College, Solapur. A total of 282 ADR reports were analysed for frequency, severity, implicated medications, patient demographics, and associated clinical factors. Causality assessment was performed using the WHO- Uppsala Monitoring Centre scale. Results: The majority of ADRs were associated with the oral route of drug administration (79.43%), and most were categorized as minor severity (68.44%) and probable causality (91.84%). Common ADR symptoms included vomiting (9.55%) and rash (9.22%). Antimicrobial agents were the most suspected drugs causing ADRs (17.38%). The study revealed discrepancies in ADR reporting patterns and highlighted the importance of pharmacovigilance in capturing and addressing ADR occurrences. Conclusion: Our study provides valuable insights into the prevalence, patterns, and characteristics of ADRs, emphasizing the need for continued surveillance and reporting to promote patient safety and improve healthcare outcomes. Strategies to improve ADR reporting and enhance medication safety protocols are warranted to optimize patient care.

Gastroparesis treatment options metoclopramide and prucalopride: analysis of the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis. Research design and methods The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions. Results Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride. Conclusions This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

Cutaneous Adverse Drug Reactions to Antidiabetic Medications and Medical Devices Used in Management of Diabetes Mellitus

Context: Approximately 537 million adults (20 - 79 years) worldwide suffer from diabetes, a number that is estimated to reach 643 million by 2030. With the rising prevalence of diabetes, pharmacological therapy has become a cornerstone for its management. The advent of newer devices and drug categories has led to a multitude of adverse drug reactions, with a significant portion being cutaneous side effects. Given that the majority of patients are on multiple other medications, such as oral hypoglycemic agents, antihypertensives, and drugs for coronary artery disease and dyslipidemia, establishing the specific cause of adverse reactions can be challenging. Since the major step in management depends on avoiding or regulating the dose of the culprit drug, it is crucial for the treating clinician to be aware of the common adverse drug reactions associated with these medications. Objective: The article aims to review the reported cutaneous adverse events of oral hypoglycemic agents, insulin, and newer devices in the management of diabetes mellitus. Evidence Acquisition: A PubMed search was conducted using the keywords 'diabetes,' 'cutaneous side effects,' 'insulin,' 'OHA,' 'sulfonylureas,' 'metformin,' and 'antidiabetic drugs.' Results: New adverse events for each category of drugs are continually being identified and reported. These adverse events range from mild rash/pruritus to severe, life-threatening allergies. Conclusions: The management of any adverse reaction includes identifying and avoiding the causative agent. However, with limited literature on the cutaneous side effects of antidiabetic therapeutics, and many being case reports, it can be difficult for clinicians to diagnose these reactions. Our article provides a concise review of the vast spectrum of cutaneous side effects that these drugs and devices can cause, along with diagnostic tests and management strategies.

Pattern of Adverse Drug Reactions in Extremes of Age Group Reported to a Tertiary Care Hospital

ABSTRACT Background: The World Health Organization (WHO), defined adverse drug reactions (ADRs) as “any noxious and unintended response to a drug, which occurs at doses normally used in humans for prophylaxis, diagnosis and treatment of the disease or for the modification of physiological functions.” Pediatrics (≤12 years) and geriatrics (≥65 years) are the extreme age groups that are more vulnerable for ADRs. Aim and Objectives: To determine ADRs time-plausible relationship, clinical spectrum, causality, and severity in extreme age group patients. Materials and Methods: All the ADRs reported to ADR monitoring center among geriatrics and pediatrics patients after Institutional Ethics Committee approval were collected from January 2015 to July 2022. The collected reports were analyzed for ADR pattern, drug groups, Causality (as per WHO-Uppsala Monitoring Centre scale) and severity (Modified Hartwig scale). Results: Out of 4705 ADRs, 176 (3.74%) were reported in geriatric and 181 (3.84%) in pediatric patients. In geriatric patients, anti-neoplastic drugs followed by cardiovascular drugs were the most commonly implicated drugs, erythematous rash and dyspnea were the most common ADRs. Erythematous rash and diarrhea were the most commonly ADRs and immunological agents followed by antimicrobials were implicated drugs in pediatric patients. In geriatric patients 84.1% were mild, 14.8% moderate, and 1.1% severe reactions whereas in pediatric group 91.2% were mild, 8.3% moderate, and 0.5% severe ADRs. Two cases of toxic epidermal necrolysis and one case of Steven–Johnson syndrome were reported in geriatric and pediatric patients respectively. Causality assessment of the majority of ADRs in geriatric age group was possible (79.5%) and in pediatric age group it was probable (61.3%). Conclusion: Extreme age group populations are more vulnerable to ADRs due to comorbidities, polypharmacy and drug interactions in elderly people and immature hepatobiliary and renal systems in pediatric age. Hence, active surveillance of drugs and education of prescribers will help to minimize the risk of ADRs in this susceptible population.

CYP2C19 polymorphisms on escitalopram treatment outcome in South Indian population with major depressive disorder

Various CYP2C19-mediated metabolizer groups may arise as a result of inter-individual variability, which potentially influences the efficacy and safety of escitalopram. Hence, it is crucial to establish a comprehensive collection of information relevant to each phenotype regarding the efficacy and tolerability of therapy. This will enable psychiatrists to make optimal decisions for individual patients. The aim of the study: The aim of this study is to classify MDD patients into various CYP2C19 metabolizer groups and to determine the association between phenotype and treatment outcome. Materials and Methods: The study enrolled 119 escitalopram monotherapy-treated MDD patients aged 18–58. MADRS, HDRS-17, and CGI were used to measure efficacy at baseline, weeks 4, 8, and 12. Safety and tolerability outcomes were examined from occurring ADRs. Clinical outcomes were compared among phenotypes based on changes in HDRS-17 and CGI scores from week 4 to week 12. Results: Subjects were categorized by CYP2C19 genotype: 20 poor (PM), 64 intermediate (IM), 24 extensive (EM), and 11 ultra-rapid (UM) metabolizers. Response and remission occurred in 67.2 % and 26.8 % of the 119 subjects at the end of the 12th week of the study. The response rate in PM was much lower (21.6 %) compared to EM. There were 312 adverse drug reactions (ADRs), and 88 (73.94 %) individuals had at least one. In safety data, nervousness was the most common ADR among the four groups 66 (55.4 %), followed by decreased appetite 48 (40.3 %). There were no severe ADRs. Men had more ADRs than women. Conclusion: CYP2C19 genotyping may help personalize escitalopram medication. The study found that the reduced ability of PM to metabolize escitalopram is probably associated with the decreased efficacy and tolerance shown in PM compared to EM and IM. The relationship between metabolizer status and treatment response followed the anticipated direction. Our findings should guide future clinical studies that include pharmacokinetic assessments

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

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.

Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis.

The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index. We conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria. Our investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale. Drug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.

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.