Occurrence Of Adverse Drug Reactions Research Articles

A Prospective Observational Study to Evaluate the Prevalence of Adverse Drug Reactions and its Impact on Quality of life in Psychiatric Patients at a Tertiary Care Teaching Hospital

Background: In recent times, emphasis on pharmacovigilance (PV) is elevated due to increased cases of adverse drug reactions (ADRs) coming into notice. Psychotropic medications that are the mainstay of treating psychiatric patients are linked to various adverse drug reactions. The given study lays accentuation on determining the pattern of ADRs due to the use of antipsychotics and antidepressants. Objectives: In this study, we aim to determine the incidence of ADRs and their effect on the quality of life (QOL) of the patients after the ADR (s). Methodology: This is a prospective observational study of a total of 300 subjects receiving antipsychotics and/or antidepressants. They were screened for possible ADRs. Possible risk factors for the development of ADRs were also assessed. The difference in the pattern of ADRs in patients prescribed with Antidepressants (ADs) and/or Antipsychotics (APs) was observed. The average number of APs and/or ADs per prescription was calculated. The causality and severity assessment of the observed ADRs was done by the World Health Organization-Uppsala Monitoring Center (WHO-UMC) scale, Naranjo’s algorithm, and Hartwig–Siegel scale, respectively. Lastly, the impact of ADRs on the QOL of the patients receiving APs and/or ADs was evaluated. Results: The prevalence of ADRs in patients receiving APs and/or ADs is 24.33%. Olanzapine is the most commonly prescribed AP while sertraline is the most commonly prescribed AD. Olanzapine and sertraline are responsible for the highest number of ADRs as AP and AD, respectively. Females are found to be at higher risk for developing ADRs. Multiple comorbidities and polypharmacy are also considered to be possible risk factors. The average number of APs and/or antidepressants per prescription is 1.94 drugs. APs are found to be responsible for a higher number of ADRs in comparison with ADs. The maximum number of ADRs falls into the possible criteria of causality assessment by the WHO-UMC scale and Naranjo’s algorithm. All the observed ADRs fall into the mild and moderate category of severity by the Hartwig–Siegel scale. The ADRs have a significant impact on the physical health and psychological domain of QOL assessment. Conclusion: The need for PV is highlighted by the results obtained in this study. Intense monitoring and increased awareness can help improve the rate of ADR (s) occurrence in patients receiving psychotropic medications. As a result, the impact of ADRs on the QOL of the patients can also be reduced.

Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.

In Africa, the burden of hypertension has been rising at an alarming rate for the last two decades and is a major cause for cardiovascular disease (CVD) mortality and morbidity. Hypertension is characterised by elevated blood pressure (BP) ≥ 140/90 mmHg. Current hypertension guidelines recommend the use of antihypertensives belonging to the following classes: calcium channel blockers (CCB), angiotensin converting inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, β-blockers, and mineralocorticoid receptor antagonists (MRAs), to manage hypertension. Still, a considerable number of hypertensives in Africa have their BP uncontrolled due to poor drug response and remain at the risk of CVD events. Genetic factors are a major contributing factor, accounting for 20% to 80% of individual variability in therapy and poor response. Poor response to antihypertensive drug therapy is characterised by elevated BPs and occurrence of adverse drug reactions (ADRs). As a result, there have been numerous studies which have examined the role of genetic variation and its influence on antihypertensive drug response. These studies are predominantly carried out in non-African populations, including Europeans and Asians, with few or no Africans participating. It is important to note that the greatest genetic diversity is observed in African populations as well as the highest prevalence of hypertension. As a result, this warrants a need to focus on how genetic variation affects response to therapeutic interventions used to manage hypertension in African populations. In this paper, we discuss the implications of genetic diversity in CYP11B2, GRK4, NEDD4L, NPPA, SCNN1B, UMOD, CYP411, WNK, CYP3A4/5, ACE, ADBR1/2, GNB3, NOS3, B2, BEST3, SLC25A31, LRRC15 genes, and chromosome 12q loci on hypertension susceptibility and response to antihypertensive therapy. We show that African populations are poorly explored genetically, and for the few characterised genes, they exhibit qualitative and quantitative differences in the profile of pharmacogene variants when compared to other ethnic groups. We conclude by proposing prioritization of pharmacogenetics research in Africa and possible adoption of pharmacogenetic-guided therapies for hypertension in African patients. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.

Safety and Effectiveness of Alirocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor, in Patients With Familial or Non-Familial Hypercholesterolemia - A Post-Marketing Survey (J-POSSIBLE).

This study evaluated the safety and effectiveness of alirocumab in Japanese patients with familial hypercholesterolemia (FH) or non-FH in a real-world clinical setting. This post-marketing surveillance study had a 2-year standard observation period. The study included Japanese patients with hypercholesterolemia who were treatment naïve to alirocumab, had a high risk of developing cardiovascular events, and had an insufficient response to, or were unsuitable for, treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Alirocumab was administered at a dose of 75 or 150 mg via subcutaneous injection every 2 or 4 weeks. Overall, 1,177 and 1,038 patients were included in the safety and effectiveness analysis populations, respectively. The incidence of adverse drug reactions (ADRs) was 3.4% (40/1,177). The time to ADR occurrence was within 4 weeks in half the patients experiencing ADRs (n=20). There were no meaningful differences in the ADRs experienced in the FH and non-FH groups. The mean (±SE) percentage changes in low-density lipoprotein cholesterol from baseline to last observation carried forward were -46.9±2.1% and -42.7±2.0% in the non-FH and FH groups, respectively. Total cholesterol, triglycerides, apolipoprotein B/E, and lipoprotein(a) concentrations were decreased at Week 4 and maintained until Week 104 in the overall population. Alirocumab was well tolerated and showed effectiveness in Japanese patients with hypercholesterolemia in a real-world clinical setting.

A real-life pilot study of the clinical application of pharmacogenomics testing on saliva in epilepsy.

Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty-one individuals (median age [Q1 -Q3 ]: 15 [6.5-28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug-resistance (3435 CC) or drug-sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs.

The therapeutic concordance approach reduces adverse drug reactions in patients with resistant hypertension.

Adverse drug reactions (ADRs) remain among the leading causes of therapy-resistant hypertension (TRH) and uncontrolled blood pressure (BP). We have recently reported beneficial results in BP control in patients with TRH adopting an innovative approach, defined as therapeutic concordance, in which trained physicians and pharmacists reach a concordance with patients to make them more involved in the therapeutic decision-making process. The main scope of this study was to investigate whether the therapeutic concordance approach could lead to a reduction in ADR occurrence in TRH patients. The study was performed in a large population of hypertensive subjects of the Campania Salute Network in Italy (ClinicalTrials.gov Identifier: NCT02211365). We enrolled 4,943 patients who were firstly followed-up for 77.64 ± 34.44 months, allowing us to identify 564 subjects with TRH. Then, 282 of these patients agreed to participate in an investigation to test the impact of the therapeutic concordance approach on ADRs. At the end of this investigation, which had a follow-up of 91.91 ± 54.7 months, 213 patients (75.5%) remained uncontrolled while 69 patients (24.5%, p < 0.0001) reached an optimal BP control. Strikingly, during the first follow-up, patients had complained of a total of 194 ADRs, with an occurrence rate of 68.1% and the therapeutic concordance approach significantly reduced ADRs to 72 (25.5%). Our findings indicate that the therapeutic concordance approach significantly reduces ADRs in TRH patients.

Impact of COVID-19 on Adherence to Treatment in Patients with HIV.

In patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student's t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence.

Lidocaine 10% sprays versus oral diclofenac sodium for pain relief in women undergoing hysterosalpingography for infertility workup: A randomized clinical trial

ABSTRACT Background Tubal disease is the leading cause of female infertility in the West African sub-region and hysterosalpingography (HSG) is the first-line imaging technique in its assessment. HSG is an acutely painful procedure. Various studies on analgesia for HSG were inconclusive. We compared the efficacy of 10 mg lidocaine 10% spray and 50 mg oral diclofenac sodium for pain relief during HSG. Methods This randomized clinical trial was carried out at the Department of Obstetrics and Gynecology, Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC) Ile-Ife, Nigeria between December 2019 and December 2021, among one hundred and eight eligible women undergoing HSG as part of their infertility workup. Ethical clearance was obtained from the ethics committee of the hospital with Protocol number ERC/2019/01/14. They were randomized into two groups. One group of 54 patients received 10 mg of 10% lidocaine spray and an oral placebo, while the second group of 54 women had 50 mg of oral diclofenac sodium and normal saline spray. Pain scores were assessed using a 10 cm visual analog scale at cervical traction, instillation of contrast media, and thirty minutes after HSG. The mean pain scores, the need for additional analgesia, and the occurrence of adverse drug reactions were compared between the two groups. Result Those in the oral diclofenac group had significantly lower pain scores than the 10% Lidocaine group 30 minutes after HSG; 1.13 ± 1.06 Vs. 2.04 ± 1.26 (p < 0.001). The additional analgesic requirement also showed no statistically significant difference between the two groups. Conclusion This study showed that oral diclofenac sodium is comparable to lidocaine spray for pain relief during HSG. It also has the additional benefit of improved quality of life 30 mins after HSG as evidenced by effective pain relief. Consideration should be given to the use of oral diclofenac sodium for pain relief during and after HSG in well-selected patients.

Reports analysis of psychotropic drugs related adverse reactions in Australia and Poland during the COVID 19 pandemic

BackgroundThe COVID-19 pandemic has caused significant changes to the global health care system AimsIt is unknown whether the COVID-19 pandemic influenced the occurrence of adverse drug reactions (ADR) of antidepressive agents, benzodiazepines, and antipsychotics plus mood stabilizers (AaMS). The study was designed in order to compare the incidence of ADR during the COVID-19 pandemic with the period preceding the pandemic in Poland and Australia, different in terms of their COVID-19 prevention strategy. MethodWe analysed ADR from the three surveyed pharmacological groups of drugs observed in Poland and Australia in the period prior to, and during the COVID-19 pandemic ResultsIn Poland, a noticeable increase in the reported ADR of the assessed drug groups was observed during the COVID-19 pandemic. The highest was for antidepressive agents, but the reporting of ADR for benzodiazepines and AaMS drugs also increased significantly. In the case of ADR in Australian patients, the increase in the number of reported ADR for antidepressive agents was modest compared to that seen in Poland, but still noticeable, and there was a significant increase in ADR for benzodiazepines ConclusionsThis study showed that the COVID-19 pandemic has had an impact on the incidence of ADR reported among both Polish and Australian patients but the modality of this was different.

Abstract 3157: Prediction of adverse drug reactions of anti-breast cancer drugs using machine learning

Abstract Chemotherapy is a representative treatment option for cancers, but one of the challenges during the course of cancer treatment is the possible occurrence of adverse drug reactions (ADRs) caused by an anticancer drug. For example, ADRs such as encephalopathy, radiation recall dermatitis, acute cardiogenic shock and febrile neutropenia have been reported for 5-fluorouracil, an anticancer drug used to treat several cancer types. These ADRs may be caused by a single drug or by interactions with other drugs. Unfortunately, it is extremely difficult to predict potential ADRs a priori because the occurrence of ADR depends on the patient’s genetics and health condition as well as a combination of drugs taken together. To address this problem, we use electric health record (EHR) data of breast cancer patients as a proof-of-concept demonstration to develop a machine learning model that predicts ADRs. For this, administrations of breast cancer patients, diagnostic records, and additional personal information (e.g., age and gender) were used as input data. To deal with high sparsity of EHR data, which has categorical information, factorization machine was applied. Factorization machine can effectively capture key information in an sparse environment. The model classifies whether a patient shows one of pre-defined ADRs as an output. The machine learning model developed in this study can be useful for predicting potential ADRs of various drugs by taking into account a patient’s health condition. Citation Format: Kang Seongmo, Suehyun Lee, Hyunah Shin, Hyun Uk Kim. Prediction of adverse drug reactions of anti-breast cancer drugs using machine learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3157.

A real-world data analysis of topotecan in the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Objectives The objective of this study was to monitor and identify adverse events (AEs) associated with topotecan, a medication used for the treatment of solid tumors, in order to improve patient safety and guide medication usage. Methods To assess the disproportionality of topotecan-related AEs in real-world data, four algorithms (ROR, PRR, BCPNN, and EBGM) were employed as measures to detect signals of topotecan-associated AEs. Results A statistical analysis was conducted using data from the FAERS database, encompassing 9,511,161 case reports from 2004Q1 to 2021Q4. Among these reports, 1,896 were identified as primary suspected (PS) AEs related to topotecan, and 155 topotecan-related adverse drug reactions (ADRs) at the preferred terms (PTs) level were selected. The occurrence of topotecan-induced ADRs was analyzed across 23 organ systems. The analysis revealed several expected ADRs, such as anemia, nausea, and vomiting, which were consistent with the drug labels. Additionally, unexpected significant ADRs associated with eye disorders at the system organ class (SOC) level were identified, indicating potential adverse effects not currently mentioned in the drug instructions. Conclusion This study identified new and unexpected signals of adverse drug reactions (ADRs) related to topotecan, providing valuable insights into the relationship between ADRs and topotecan usage. The findings highlight the importance of ongoing monitoring and surveillance to detect and manage AEs effectively, ultimately improving patient safety during topotecan treatment.

Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase®, the WHO Pharmacovigilance Database.

Alongside their BCR-ABL specificity, TKIs used in chronic myeloid leukemia also target other tyrosine kinases expressed in the kidney such as PDGFR, c-KIT, SRC, and VEGFR, which may result in specific renal adverse drug reaction (ADR). To evaluate the renal safety profile in real-life conditions, a case/non-case study was performed on VigiBase®, the WHO global safety database. From 7 November 2001 to 2 June 2021, all cases in which the involvement of imatinib, dasatinib, nilotinib, bosutinib, and ponatinib was suspected in the occurrence of renal ADR were extracted from VigiBase®. Disproportionality analyses were assessed using the reporting odds ratio. A total of 1409 cases were included. Imatinib accounts for half of the reported cases. A signal of disproportionate reporting (SDR) of renal failure and fluid retention was found for the five TKIs. Only dasatinib and nilotinib were related to an SDR for nephrotic syndrome. Nilotinib and ponatinib were related to an SDR for renal artery stenosis, while dasatinib was related to an SDR for thrombotic microangiopathy. No SDR for tubulointerstitial nephritis was observed. This study identified a new safety signal, nephrotic syndrome, for nilotinib and highlights the importance of post-marketing safety surveillance.

Assessment of Amikacin- and Capreomycin-Related Adverse Drug Reactions in Patients with Multidrug-Resistant Tuberculosis and Exploring the Role of Genetic Factors.

Following the introduction of all-oral treatment regimens for patients with drug-resistant tuberculosis (TB), second-line injectable drug applications have been reduced in the last few years. However, they are still important for anti-TB therapy. This study aims to analyze the occurrence of amikacin- and capreomycin-related adverse drug reactions (ADR) in patients with multidrug-resistant tuberculosis (MDR-TB) and evaluate the role of multiple patient-, disease-, and therapy-related factors on the frequency of the observed adverse events. In addition, the possible role of genetic risk factors was studied by full-length mitochondrial DNA sequencing. Toward this aim, we retrospectively evaluated 47 patients with MDR-TB who received amikacin and/or capreomycin. In total, 16 (34.0%) patients developed ototoxicity and 13 (27.7%) developed nephrotoxicity, including 3 (6.4%) patients who experienced both adverse events. Ototoxicity development was more common in patients who received amikacin. No other factors showed a significant impact. Nephrotoxicity was likely associated with previous renal health impairment. Full mitochondrial genome sequencing did not reveal any specific ADR-associated variants, and results showed no differences in adverse event occurrence for any specific variants, mutation count, or mitochondrial haplogroup. The absence of the previously reported ototoxicity-related mtDNA variants in our patients with ototoxicity and nephrotoxicity highlighted the complex nature of the ADR occurrence.

The immediate adverse drug reactions induced by ShenMai Injection are mediated by thymus-derived T cells and associated with RhoA/ROCK signaling pathway.

The mechanism of the immediate adverse drug reactions (ADRs) induced by ShenMai injection (SMI) has not been completely elucidated. Within 30 minutes, the ears and lungs of mice injected with SMI for the first time showed edema and exudation reactions. These reactions were different from the IV hypersensitivity. The theory of pharmacological interaction with immune receptor (p-i) offered a new insight into the mechanisms of immediate ADRs induced by SMI. In this study, we determined that the ADRs were mediated by thymus-derived T cells through the different reactions of BALB/c mice (thymus-derived T cell normal) and BALB/c nude mice (thymus-derived T cell deficient) after injecting SMI. The flow cytometric analysis, cytokine bead array (CBA) assay and untargeted metabolomics were used to explain the mechanisms of the immediate ADRs. Moreover, the activation of the RhoA/ROCK signaling pathway was detected by western blot analysis. In BALB/c mice, the vascular leakage and histopathology results showed the occurrence of the immediate ADRs induced by SMI. The flow cytometric analysis revealed that CD4+ T cell subsets (Th1/Th2, Th17/Treg) were imbalanced. And the levels of cytokines such as IL-2, IL-4, IL12P70 and INF-γ increased significantly. However, in BALB/c nude mice, all the indicators mentioned above have not changed significantly. The metabolic profile of both BALB/c mice and BALB/c nude mice was significantly changed after injecting SMI, and the notable increase in lysolecithin level might have a greater association with the immediate ADRs induced by SMI. The Spearman correlation analysis revealed that LysoPC (18:3(6Z,9Z,12Z)/0:0) showed a significant positive correlation with cytokines. After injecting SMI, the levels of RhoA/ROCK signaling pathway-related protein increased significantly in BALB/c mice. Protein-protein interaction (PPI) showed that the increased lysolecithin levels might be related to the activation of the RhoA/ROCK signaling pathway. Together, the results of our study revealed that the immediate ADRs induced by SMI were mediated by thymus-derived T cells, and elucidated the mechanisms of such ADRs. This study provided new insights into the underlying mechanism of immediate ADRs induced by SMI.

Predictors of antibiotic use in pregnant women attending Najran University Hospital, Saudi Arabia.

To determine the prevalence of antibiotic use by pregnant women in Najran, Saudi Arabia. A total of 125 women aged 18 to 45 with a full-term pregnancy participated from October to December 2019. Age, order of current pregnancy, body mass index (BMI), history of miscarriage, and comorbidity were used to estimate antibiotic use. The majority were Saudis (67.2%), aged 30-35 (39.2%) years, with no history of miscarriage (53.6%), second order of pregnancy (26.4%), and going through weeks 20-25 of pregnancy (21.6%). A total of 26.4% of pregnant women had antibiotic prescriptions in the study population. Pregnant women under 30 years were less likely to receive antibiotics. The results found an association between maternal age, order of pregnancy and antibiotic use during pregnancy. An association was observed between maternal BMI and the occurrence of adverse drug reactions after antibiotic use. In addition, a history of miscarriage was negatively associated with the use of antibiotics during pregnancy. These predictors of antibiotic administration have the potential to serve as general health indicators and to direct preventative strategies aimed at increasing the rational use of antibiotics.

Adverse drug reactions in geriatric psychiatry—retrospective cohort study of a 6-year period

ObjectiveTo investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period.DesignRetrospective monocentric cohort study.ResultsSix hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37–6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23–0.89).ConclusionsType and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.

Impact of polymorphisms in CYP and UGT enzymes and ABC and SLCO1B1 transporters on the pharmacokinetics and safety of desvenlafaxine.

Venlafaxine pharmacokinetic variability and pharmacotherapy outcomes are well known to be related to CYP2D6 pharmacogenetic phenotype. In contrast, scarce pharmacogenetic information is available nowadays concerning desvenlafaxine, its active metabolite first marketed in 2012. The aim of this study was to evaluate the impact of 29 alleles in 12 candidate genes (e.g., CYP enzymes like CYP2D6, CYP3A4, or CYP2C19; ABC transporters like ABCB1; SLCO1B1; and UGT enzymes like UGT1A1) on desvenlafaxine pharmacokinetic variability and tolerability. Pharmacokinetic parameters and adverse drug reaction (ADR) incidence obtained from six bioequivalence clinical trials (n = 98) evaluating desvenlafaxine formulations (five with single dose administration and one with multiple-dose administration) were analyzed. No genetic polymorphism was related to pharmacokinetic variability or ADR incidence. Volunteers enrolled in the multiple-dose clinical trial also showed a higher incidence of ADRs, e.g., xerostomia or appetite disorders. Volunteers experiencing any ADR showed a significantly higher area under the time-concentration curve (AUC) than those not experiencing any ADR (5115.35 vs. 4279.04ng*h/mL, respectively, p = 0.034). In conclusion, the strong dose-dependent relationship with the occurrence of ADRs confirms that the mechanism of action of desvenlafaxine is essentially dose-dependent.

PS-C31-11: THE RELATION BETWEEN ANTIHYPERTENSIVE DRUGS AND DIURETICS AND ADVERSE DRUG REACTIONS IN THE OLDER INPATIENTS

Aim: We investigated whether antihypertensive drugs and diuretics were associated with adverse drug reactions in the older inpatients. Methods: We retrospectively investigated factors related to adverse drug reactions(ADRs) in inpatients aged 65 and over in the geriatrics and hypertension ward of Osaka University Hospital in Japan. We identified drug information and ADRs from the medical records of 1031 inpatients during the 7 years from September 2014 to August 2021. Results: There were 94 ADRs in 81 patients(7.9%) of the total of 1031 patients (female 54.0%, mean age 78.1 ± 6.7 years), there happened the most in 24 cases is with antihypertensive drugs, and the second most in 15 casess is with diuretics. Of the 24 cases of ADRs thought to be caused by antihypertensive drugs, 20 cases of ADR occurred with antihypertensive drugs taken before admission. The details of ADRs by antihypertensive drugs were hypotention / orthostatic hypotension in 16 cases, bradycardia in 7 cases, and edema in 1 case. Of the 15 cases of ADRs thought to be caused by diuretics, 10 cases of ADRs occurred with diuretics that had been taken before admission. The details of ADRs by diuretics were electrolyte abnormalities in 8 cases, hypotension / orthostatic hypotension in 6 cases, and renal dysfunction in 1 case. Of the 24 cases in which antihypertensive drugs were suspected to be ADRs, the most common disease were heart failure in 7 cases, followed by hypertension in 4 cases. Of the 15 cases in which diuretics were suspected to be ADRs, the most common diseases were heart failure (3 cases) and diabetes (3 cases). However, the results of multivariate analysis showed no significant association between the disease that triggered admission and the occurrence of ADRs. Conclusions: The subjects of this study included many patients with hypertension and heart failure, and since they used many antihypertensive drugs and diuretics, there were many ADRs caused by them. The same situation seems to be naturally accepted in medical care for the older people. It is important to be aware that antihypertensive drugs and diuretics, being the most common in medical care for the older people, may cause ADRs.

A study of drug utilization pattern, safety, and drug interactions in pediatric intensive care unit at tertiary care hospital

Background: Conducting drug utilization studies are crucial, particularly for pediatric patients, as it helps improve the prescribing patterns and usage of medications in the health-care system. However, there is a scarcity of research on the utilization of drugs in children, making this study an invaluable resource for understanding prescription patterns. Aims and Objectives: Main objectives behind our study were to examine and evaluate such prescription pattern in detail including antibiotics usage and prescription analysis using core drug prescribing indicators given by the World Health Organization (WHO), to evaluate adverse drug reactions that are observed during study and to evaluate drug-drug interactions (DDIs). Materials and Methods: This is an observational cross-sectional study of 12-month duration started after intuitional ethical committee approval. Total 450 prescriptions were studied. The study included all patients, regardless of gender, who were admitted to the pediatric intensive care unit (PICU). Results: Our study found that the average number of drugs per prescription was 4.87. In addition, a high percentage of drugs, specifically 97.39%, were prescribed using their generic names, while 94.84% of drugs prescribed were from the WHO essential drug list for children. Moreover, we observed that in 88.88% of encounters, antibiotics were prescribed and percentage of prescriptions, in which drugs were prescribed through injectable route, was 98.22%. Very minimal amount of adverse drug reaction was seen in patients. In our study, in 75.77% of the prescriptions, DDIs were not found. Conclusion: The study found that generic names of drugs were frequently used, and a high percentage of drugs prescribed were from the WHO essential drug list. However, the study also revealed a high percentage of encounters with antibiotics and injections prescribed. The occurrence of adverse drug reactions was minimal in the study. Moreover, most prescriptions did not exhibit DDIs, indicating appropriate therapeutic management in the PICU.

Adverse drug reactions and associated factors in multidrug-resistant tuberculosis: A retrospective review of patient medical records at Mbarara Regional Referral Hospital, Uganda.

The World Health Organization pragmatic guidelines recommend shorter duration drug regimens with newer, more efficacious agents for treatment of multidrug-resistant tuberculosis. However, adverse drug reactions associated with the use of newer, second-line agents may pose a major barrier to adequate management of multidrug-resistant tuberculosis. We therefore sought to investigate the prevalence and factors associated with adverse drug reactions among patients with multidrug-resistant tuberculosis. We retrospectively reviewed patient medical records at the tuberculosis treatment unit of Mbarara Regional Referral Hospital, between January 2013 and December 2020. Medical records were included in the study, if the patients were aged ⩾18 years, tested sputum positive for multidrug-resistant tuberculosis, with adequate pharmacovigilance data documented. We assessed all documented health-related patient complaints, deranged laboratory values, and clinician suspected adverse drug reactions for scientific/clinical plausibility. Adverse drug reactions were confirmed using published and manufacturer drug references materials. A multidisciplinary clinician team was involved to decide whether to exclude or include a suspected adverse drug reaction. About 6 in 10 (67.4%; 120/178) patients experienced at least one adverse drug reactions during treatment, of which 18.3%, 14.6%, and 11.4% of adverse drug reactions affected the endocrine/metabolic, otic, and musculoskeletal body systems, respectively. Majority of the adverse drug reactions were probable and had a moderate severity. There was an upward trend in adverse drug reaction incidence between 2015 and 2019. Adverse drug reaction occurrence was associated with previous adverse drug reaction history (adjusted odds ratio = 2.85 (1.08, 7.53 at 95% confidence interval)); however, patients who were underweight (adjusted odds ratio = 0.34 (0.16, 0.69 at 95% confidence interval)) and those treated with bedaquiline-based drug regimens (adjusted odds ratio = 0.2 (0.07, 0.59 at 95% confidence interval)) were less likely to experience an adverse drug reaction. Majority of patients with multidrug-resistant tuberculosis experience at least adverse drug reaction during the course of treatment. The newer standard shorter duration drug regimens (9-12 months) may be associated with intolerable adverse drug reactions that hamper effective management of multidrug-resistant tuberculosis. There is need for more studies to assess the clinical adverse drug reaction burden associated with the implementation of shorter duration regimens.

Adverse drug reactions in children and adolescents on daily antitubercular regimen: An observational longitudinal study

ObjectivesSubsequent to introduction of daily fixed dose combination (FDC) regimen with increased dosages and inclusion of ethambutol in continuation phase of antitubercular therapy (ATT) in India, this study was done to evaluate adverse drug reactions (ADRs) in children and adolescents. MethodsLongitudinal observational study conducted in tertiary teaching hospital. Children (1 month–18 year), with newly diagnosed drug sensitive tuberculosis, started on daily FDC regimen of ATT, were included. Participants were followed up at 2 weeks, 8 weeks and 6 months. Division of AIDS (DAIDS) severity grading and World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment was done. ResultsIn 99 participants, 29 experienced ADRs. Most commonly ADRs involved hepatobiliary (11.1%) and gastrointestinal (8.1%) systems. Grade 3 severity noted in 35.5% ADRs. Certain causality classified in 19.3%. Presence of ADRs was significantly higher in participants with vs without malnutrition [40.5% vs 21.1% (p = 0.036)]. Tendency for more severe ADRs noted in participants with vs without malnutrition [Grade 3 ADRs out of all ADRs: 64.7% vs 0% (p < 0.001)]. ConclusionIncidence and severity of ADRs has increased after introduction of daily FDC of ATT. Most common ADR observed were hepatobiliary. Malnutrition and less weight for age were risk factors for occurrence and severity of ADRs.