Severe Adverse Drug Reactions Research Articles

A Retrospective Study on Adverse Drug Reaction Monitoring in A Tertiary Care Hospital

Adverse drug reactions (ADRs) are a major concern in clinical practice. Reporting of ADRs either through health care professionals or the patients themselves is of utmost importance to give an accurate estimate of the prevalence, severity and preventability of ADRs. Present study was conducted to evaluate the prevalence of adverse drug reactions in a tertiary care hospital in Hyderabad, Telangana, India. This was a retrospective observational study, extending over 3 months (December 2020 to February 2021). A total of 41 cases comprising patients of either sex or age group were studied. The data was collected using CDSCO ADR reporting form. A total of 41 ADRs were reported during the three months period of study. During the study period a total of 41 ADR reports were received from various departments of the hospital. We observed 25 ADRs in females and 16 ADRs in males from our study. Among the age groups, 3 ADRs in age group 0 – 19 Yrs., 28 ADRs were seen in age group 20 – 59 Yrs., and 10 ADRs were seen in age group >60 Yrs. Maximum number of ADRs came from General Medicine department 17 (41.46%). Drug therapy 41 (100%) and diseases 19 (46.34%) were the most prominent predisposing factors of ADRs seen in our hospital. Causality assessment of suspected drugs was assessed using Naranjo scale. According to Naranjo scale most of the reported ADRs were found to be probable 23 (56.9%) followed by possible 16 (39.02%) and definite 2 (4.8%). The severities of the reactions were done using Hart Wig Scale. Majority of the reactions were mild 25 (60.97%). Withdrawal of the drug 5 (12.19%) was the main line of the management of the adverse drug reactions in the present study. Majority of serious ADRs were preventable in our study. ADRs are a major cause of morbidity worldwide. Frequency of ADRs can be reduced by careful follow up and a robust hospital-based pharmacovigilance setup. A measure to improve detection and reporting of adverse drug reactions by all health care professi

ADVERSE DRUG REACTIONS AMONG DRUG-RESISTANT TUBERCULOSIS TREATMENT: AN OBSERVATIONAL COHORT STUDY

Objective: Adverse drug reaction (ADR) is regarded as one of the major challenges in the treatment of drug-resistant tuberculosis (DR-TB). It can lead to non-compliance or interrupting treatment completion, which can contribute to avoidable morbidity, drug resistance, treatment failure, reduced quality of life, or mortality. Methods: A retrospective cohort study was conducted in the Ernakulam district of Kerala from 2016 to 2019. All DR-TB patients registered under the DR-TB center were enrolled in the study. Due to privacy and confidentiality HIV infected patients and patients below 12 y of age were excluded in this study and only the data with ADR reported by patients is collected from medical records. Results: Out of the total 146 patients, about 75 % of patients experienced at least one ADR during treatment, and a total of 208 ADRs were reported. Among all the ADRs, the most common ADR was gastritis (12.98%) followed by ototoxicity (10%) and vomiting (5.76%), etc. It was found that males (78.76%) within the age group 46-65 y exhibited more ADR than females. Some of the ADR requires drug withdrawal and replacement with other drugs and most of the patients also needed symptomatic treatment without modifying the treatment regimen. All ADR reported were collected and causality assessment was done via WHO and Naranjo scale. The majority of ADR belongs to the “probable” category in the WHO scale and Naranjo scale. The evaluation of the severity of ADR by using the Modified Hartwig and Siegel scale indicated that most of the ADR was of moderate level showing a 4b reaction. The study also assessed the preventability of ADR using the Schumock and Thornton preventability scale. Conclusion: Many of the ADRs were unidentified or not reported due to several reasons like milder ADR, patient lack of knowledge, Negligence of symptoms, unawareness of health providers, etc. Whereas the long-term treatment and diversities in age, gender, etc. were found as major contributors to ADR along with comorbidities. New drugs in combination with existing drugs created the potential for previously unnotified reactions. Pharmacovigilance should address the safety of therapy and identify ADRs, especially the serious ones with routine monitoring to prevent mortality, morbidity, and other negative outcomes.

Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine.

Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ-induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ-induced SCARs in large sample sizes and well-defined SCARs patients. Ninety-one CBZ-induced SCARs Thai patients and 144 CBZ-tolerant patients were enrolled in the study. The genotypes of HLA-A, HLA-B and EPHX1 were determined. Only 2 HLA alleles including HLA-B*15:02 and HLA-A*24:07 were statistically significant association with CBZ-induced SJS/TEN. The highest risk was observed in patients with HLA-B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24-97.09, corrected P-value = 6.80 × 10-29 ). Moreover, HLA-B75 serotypes were significantly associated with CBZ-induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39-202.56, corrected P-value = 3.84 × 10-34 ). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ-induced SCARs. The HLA-B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA-B75 serotype increases sensitivity for prediction of a life-threatening SCARs caused by CBZ.

Cephalosporin-Induced Atypical DRESS Syndrome; a Tale of Two Cases

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, idiosyncratic subset of drug-induced hypersensitivity syndrome manifesting as skin eruption, fever, lymphadenopathy, hematologic abnormalities, and multi-organ involvement. It presents usually after a latent period of 2 to 6 weeks as a diffuse erythematous rash with systemic symptoms and facial edema. It is now recognized as one of the severe cutaneous adverse reactions (SCAR) associated with high mortality, chiefly because of derangement of renal or liver functions. The cutaneous morphologies can be myriad, encompassing maculopapular, exfoliative dermatitis-like, pustular, erythema multiforme-like, Stevens-Johnson syndrome-like, and toxic epidermal necrolysis-like presentations. Case Presentation: We hereby report two young males who developed pruritic exfoliating erythematous rash after taking cephalosporin with paradoxical worsening despite drug withdrawal. They were diagnosed with ‘atypical DRESS syndrome’ according to the Japanese study group severe cutaneous adverse reactions (J-SCAR) criteria and treated successfully with systemic steroids and emollients. The J-SCAR scoring and the concept of atypical DRESS are useful in situations, where either all clinical and laboratory criteria are not present simultaneously, or typical clinical presentations wherein human herpes virus-6 (HHV-6) reactivation cannot be documented. Conclusions: These two cases were used to illustrate the hitherto obscure concept of atypical DRESS syndrome that presented with compatible clinical features but did not satisfy all the requisite criteria. We also highlight cephalosporins (one of the most commonly prescribed standard group of drugs) as a plausible but infrequently reported cause of this severe adverse cutaneous drug reaction.

Pattern and impact of drug-induced liver injury in South African patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and a high burden of HIV

Epidermal necrolysis (EN), a severe cutaneous adverse drug reaction characterized by epidermal detachment, encompasses Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Stevens-Johnson syndrome affects 10% or less of the body surface area, and there is TEN of 30% or greater with SJS/TEN overlap in between. Epidermal necrolysis is a delayed T cell–mediated hypersensitivity reaction in which mortality reaches 40%, depending on variables in the prognostic Severity-of-Illness Score for Toxic Epidermal Necrolysis tool.

Motives to Report Adverse Drug Reactions to the National Agency: A Survey Study among Healthcare Professionals and Patients in Croatia, The Netherlands, and the UK.

IntroductionHealthcare professionals (HCPs) and patients have various motives to report adverse drug reactions (ADRs) to their national agency. These motives may differ between countries.ObjectiveThe aim of this study was to assess to what extent motives of HCPs and patients to report ADRs differ between countries.MethodsHCPs and patients from Croatia (HR), The Netherlands (NL), and the UK were asked to complete a web-based survey containing questions regarding demographics and ADR reporting. HCPs and patients could select all motives for reporting that applied to them, with a total of 23 and 24 motives, respectively. Descriptive statistics are presented and Chi-square tests were used to test for differences across the countries, with effect sizes calculated using Cramer’s V.ResultsIn total, 296 HCPs and 423 patients were included (60% and 32% from Croatia, 19% and 44% from NL, and 21% and 24% from the UK, respectively). For most of the motives to report or not to report an ADR, there were no differences between countries. Most HCPs from all countries would be motivated to report an ADR if there was a strong suspicion of causality (89%), if it concerned a severe/serious ADR (86%), and if it concerned an ADR for a new, recently marketed drug (77%). Most patients from all countries agreed that they would report an ADR if it concerned a severe ADR (96%), if the ADR influenced their daily activities (91%), and if they were worried about their own situation (90%). Differences across the countries (p < 0.05 and V ≥ 0.21) were observed for three and four of the HCP and patient motives, respectively. For HCPs, these differences were seen in motives related to legal obligation (65% HR, 24% NL, 38% UK), black triangle medicines (27% HR, 4% NL, 77% UK), and the reporting of well-known ADRs (53% HR, 85% NL, 69% UK). For patients, these differences were seen in motives related to a linkage between the ADR report and the medical notes (59% HR, 60% NL, 30% UK), complexity and time taken to report (25% HR, 13% NL, 40% UK), medicines purchased on the internet (59% HR, 39% NL, 65% UK), and the reporting of embarrassing ADRs (32% HR, 11% NL, 35% UK).ConclusionsHCPs’ and patients’ motives to report or not to report ADRs to the national agency were mostly similar across the three countries. Such motives can be used in general strategies to promote and increase ADR reporting. The observed differences provide guidance to further fine-tune ADR reporting at a national level.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01098-4.

A comprehensive analysis of the efficacy and safety of COVID-19 vaccines

The numbers of cases and deaths from coronavirus disease 2019 (COVID-19) are continuously increasing. Many people are concerned about the efficacy and safety of the COVID-19 vaccines. We performed a comprehensive analysis of the published trials of COVID-19 vaccines and the real-world data from the Vaccine Adverse Event Reporting System. Globally, our research found that the efficacy of all vaccines exceeded 70%, and RNA-based vaccines had the highest efficacy of 94.29%; moreover, Black or African American people, young people, and males may experience greater vaccine efficacy. The spectrum of vaccine-related adverse drug reactions (ADRs) is extremely broad, and the most frequent ADRs are pain, fatigue, and headache. Most ADRs are tolerable and are mainly grade 1 or 2 in severity. Some severe ADRs have been identified (thromboembolic events, 21–75 cases per million doses; myocarditis/pericarditis, 2–3 cases per million doses). In summary, vaccines are a powerful tool that can be used to control the COVID-19 pandemic, with high efficacy and tolerable ADRs. In addition, the spectrum of ADRs associated with the vaccines is broad, and most of the reactions appear within a week, although some may be delayed. Therefore, ADRs after vaccination need to be identified and addressed in a timely manner.

Evaluation of switching treatment from high dose of darbepoetin to lower dose of roxadustat in Japanese hemodialysis patients.

Roxadustat is one of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) that stimulates erythropoiesis and regulates the genes related to iron metabolism. The treatment of HIF-PHIs is useful compared with that of erythropoietin stimulating agent (ESA) using various instruments and procedures. Few clinical researchers have examined the efficacy and safety of switching treatment from Darbepoetin to Roxadustat in Japanese hemodialysis (HD) patients. However, HIF-PHIs have severe adverse drug reactions, such as thrombotic events. In the present study, we evaluated the lower dose of roxadustat in HD patients receiving high dose of ESA therapy. Eighteen anemic HD patients receiving an ESA, that is,, darbepoetin over 40 μg per week, were enrolled in this study. The treatment of these patients was changed to 20 mg of roxadustat three times weekly for 6months, after which doses were adjusted to achieve a hemoglobin (Hb) target of 10.0-12.0 g/dL. An increase of 58.1 ± 32.5mg roxadustat three times weekly increased Hb. It also achieved and then maintained levels within the target range at month 6. Ferritin levels of more than 100 ng/mL or TSAT levels of more than 20% were maintained during the 6-month treatment periods with oral or intravenous iron supplementation. It seems unnecessary to increase the initial dose of roxadustat for patients using high doses of ESA. It is suggested that a reconsideration of the starting dose of roxadustat in Japanese HD patients is needed. (Ikegami General Hospital, Medical Corporation SHOWAKAI、Approval number: 2020-4).

A 10-Year Single-Center Experience of Adverse Drug Reaction Monitoring

Background/Aims: Despite proper use of pharmaceuticals, adverse drug reactions (ADRs) can lead to problems related to patient safety. We analyzed the characteristics of ADRs, particularly serious adverse events (SAEs), in a single tertiary medical institution. Methods: Spontaneous ADR report data collected from 2010 to 2019 in Seoul National University Hospital were assessed. Causality was evaluated according to the World Health Organization-Uppsala Monitoring Centre criteria. Age, sex, onset, severity, seriousness, and system organ class (SOC) of ADRs and SAEs were analyzed. Results: During the study period, a total of 49,955 individual case safety reports were assessed as possible, probable, or certain. Although the number of gastrointestinal ADR reports was high (25.9%), severe cases were uncommon (2.6%). By contrast, the number of hematologic disorders was low (6.6%) but 39.2% of them were severe. Among ADRs, 10.2% were assessed as SAEs, the proportion of which was high at extreme ages and in males. Body as a whole-general disorders were the most frequently reported SOC for SAEs, followed by skin and appendage disorders. Antineoplastic agents and antibiotics were the most common causative agents of SAEs and ADRs. Anaphylactic reaction was the most frequent SAE (6.5%). Conclusions: The proportion of SAE differs according to SOC and drug. Attention should be paid to SAEs in children and older adults because the rate of SAEs is significantly higher at extreme ages.

Tardive Akathisia in an Adult on Long Term Metoclopramide

Metoclopramide is prescribed to subjects dealing with gastrointestinal issues like delayed gastric emptying, nausea, vomiting or loss of appetite. It is also used to treat chemotherapy and surgery related nausea and vomiting. Although it is very effective in targeting stomach related illnesses, severe adverse drug reactions can occur in those who take metoclopramide. This case report describes a 32-year-old female who suffered from tardive akathisia while being treated with long-term metoclopramide. Long term exposure to causative medication leads to evolution of Tardive akathisia and this can stay for a lifetime. It is important to restrict the exposure duration of triggering drug. Health care professionals and patients should be well aware of this neurological adverse event of metoclopramide.

Current Perspectives on Severe Drug Eruption.

Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA- and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management.

Adverse Drug Reactions among Children with Tuberculosis in Tashkent, Uzbekistan, 2019.

The treatment of childhood tuberculosis can be challenging due to the lack of pediatric drug formulations and monitoring of drug-toxicity in routine settings. There are no published studies from Uzbekistan on the adverse drug reactions (ADR) associated with anti-tuberculosis treatment in children. In this study, we aimed to investigate the ADR associated with anti-tuberculosis treatment in children. This was a cohort study using secondary program data of children treated at the city and regional tuberculosis clinics in Tashkent, Uzbekistan. Of the 302 patients evaluated, 135 (44.7%) reported ADR. New tuberculosis was registered in 277 (92%) patients and 262 (87%) had extrapulmonary tuberculosis. Factors associated with ADR included treatment at a regional hospital (adjusted odds ratio, aOR = 1.75; p = 0.026), female sex (aOR = 2.2; p = 0.004), and treatment with second-line drugs (aOR = 8.82; p < 0.001). The most common ADRs were gastrointestinal disorders (28.5%) followed by hepatitis (8.9%) and dermatologic reactions (8.6%). Most of the ADRs were mild (55.6%) or moderate (43.7%), only one child had severe ADR. Patients with the identified risk factors should be closely monitored during the treatment. We also recommend expansion of ADR surveillance throughout the country for more representative data in the future.

Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients.

Iron-based phosphate binders, including ferric citrate hydrate (FCH) and sucroferric oxyhydroxide (SFOH), have been used for the treatment of hyperphosphatemia in end-stage renal disease patients on dialysis. However, the long-term efficacy and safety of these agents have not yet been clearly elucidated. Laboratory data of 56 hemodialysis patients who had been prescribed either FCH (n = 33) or SFOH (n = 23) were retrospectively examined. We showed that both FCH and SFOH significantly and consistently decreased serum phosphate concentrations in the patients undergoing maintenance hemodialysis during the 36-month observation period. Serum levels of calcium, intact parathyroid hormone, as well as hemoglobin levels were unaltered. No overshoot of parameters of iron metabolism, such as transferrin saturation and serum ferritin levels, was observed, and serum ferritin level remained under 300ng/mL in most patients. A trend towards decrease in the doses of erythropoiesis-stimulating agents used and frequency of intravenous iron use was observed in both treatment groups. No severe adverse drug reactions were observed in either the patients receiving FCH or SFOH. The results of the present study suggest that the iron-based phosphate binders, FCH and SFOH, decrease serum phosphate concentrations consistently and are safe to use over the long-term in maintenance hemodialysis patients.

Efficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis: A randomized controlled trial

ObjectiveTo determine the efficacy and safety of add-on dry powder for inhalation (DPI) of combined anti-TB agents prepared as a particulate system (study group) compared with placebo DPI (control group) in patients diagnosed with pulmonary TB. MethodsThis study was a randomized, placebo-controlled, double-blinded parallel design. Subjects were pulmonary TB patients, new or re-treatment, aged 18 years or older. The eligible patients were randomly allocated (1:1) to either the study group or the control group using stratified blocked randomization. The add-on DPI of combined anti-TB therapy (each capsule contained isoniazid 5 mg, rifampicin 2 mg, pyrazinamide 16 mg, and levofloxacin 2 mg) was used throughout the course of the standard oral anti-TB treatment. The primary outcome was Mycobacterium tuberculosis (MTB) sputum culture conversion measured after receiving treatment for eight weeks. Secondary outcomes were clinical signs and symptoms of pulmonary TB and adverse drug reactions (ADRs) related to anti-TB agents. The percentages of patients who achieved the primary outcome were compared (95% confidence interval). All analyses were performed using the modified intention-to-treat principle. Results91 patients were randomly allocated: 44 to the study group and 47 to the control group. Important baseline data (%peak expiratory flow rate, chest X-ray findings, resistance to anti-TB agents, renal and liver function tests) were similar between the two groups. Although the percentages of patients who achieved the primary outcome were similar in both groups (34/44 [77.3%] in the study group and (34/47 [72.3%] in the control group; relative risk [RR] 1.07, 95% CI 0.84–1.36; p = 0.589), the study group patients seemed to achieve the primary outcome earlier than the control group (22/44 [50.0%] vs 15/47 [31.9%]; RR 1.57, 95% CI 0.94–2.61; p = 0.079) at the end of week 4. Cough was significantly lower in the study group than in the control group (23/44 [52.3%] vs 43/47 [91.5%]; RR 0.57, 95% CI 0.43–0.77; p < 0.001) at week 4 of treatment. Hemoptysis was found in approximately half of each group at baseline. The percentage of patients having hemoptysis was substantially reduced at week 2 of treatment (5 [11.4%] in the study group and 11 [23.0%] in the control group, p = 0.132). Regarding safety outcomes, no dyspnea or severe ADRs were reported. Adverse events (AEs) related to oral anti-TB agents, (e.g. liver function tests) were in normal ranges in most patients in both groups during the treatment. The incidences of common AEs reported (e.g. anorexia, dizziness, numbness, arthralgia, rash, and itching) were similar between the two groups, while the incidences of nausea and vomiting were significantly lower in the study group than the control group (38.6% vs 74.5%, p = 0.001, and 43.2% vs 66.0%, p = 0.029, respectively). ConclusionsAdd-on combined anti-TB DPI therapy to the standard oral anti-TB treatment did not increase MTB sputum culture conversion at two months of treatment. However, the percentage of patients having cough in the study group was significantly lower than in the control group at two months after treatment. A reduction in cough might represent adequate response to treatment, and result in a decreased risk of spread of infection. Combined anti-TB DPI therapy was safe. Further study investigated in a larger sample using higher strengths of DPI therapy is required.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

ABSTRACT Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests. Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Drug-induced liver injury associated with severe cutaneous adverse drug reactions: A nationwide study in Taiwan.

Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR. We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020. A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P<.003). Chronic kidney disease with high-dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol-induced DILI with SCAR. The HLA-B*5801 was associated with a high risk and mortality of allopurinol-induced DILI with SCAR. Likewise, the HLA-B*1502 was closely related to carbamazepine-induced DILI with SCAR. DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA-B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol-induced DILI with SCAR.

A Prospective Study on Adverse Drug Reactions in Inpatients of General Medicine Department in a Tertiary Care Hospital- A clinical Pharmacist-led Study

The present study was carried out to determine the incidence of Adverse Drug Reactions (ADRs) in general medicine department and to assess and analyze the causality, severity, and preventability of ADRs. A prospective observational study was conducted in the general medicine department for six months. All patients receiving drug therapy are considered and are selected based on the inclusion criteria. Patient demographic details like age, gender, diagnosis, past medical history, concomitant medications, etc., are recorded from the patient data gathering form. The causality assessment is accomplished using Naranjo and WHO scales. The severity is carried out using the Modified Hartwig and Siegel scale. The preventability evaluation is accomplished using the Modified Schmock and Thornton scale. The study included 385 patients were between the age group of 18 years and, out of which 34 patients developed adverse drug effects including female and male. Patients between the age group of 40-50 years (18.1%) developed a high incidence of ADRs. The causality was assessed using Naranjo’s causality assessment scale, 44.1% reactions were probable; 29.4% reactions were certain, 23.5% reactions were possible and 2.9 % reactions were conditional. When the reactions were assessed most of them were assessed 55.1% were moderate and 61.8% were probably preventable. Appropriate observation of the drug effect is essential to ensure the safety of the patient. This also will have the advantage of reducing the incidence of the ADRs, thus deplete the complications and helps to improve the quality of life of the patients.

Preventability, predictability, severity and causality assessment of adverse drug reactions reported from a teaching hospital in chhattisgarh: A retrospective analysis.

Background and Objectives:Adverse Drug Reactions (ADRs) can lead to significant morbidity, rarely mortality and financial burden over the patient. ADRs that can be prevented can be considered as form of medication error sometimes. This study assessed the preventability, predictability and severity of ADRs using different assessment scales.Methods:ADR Monitoring Centre under newly established teaching hospital in Chhattisgarh collected ADR reports from different healthcare professionals during the period from November 2016 to November 2018. Analysis of the reported ADRs was done for their causality assessment, demographic details of patients, most common drug class responsible for the ADR. Seriousness and preventability of ADRs were analysed by using WHO Causality Scale and Modified Schumock and Thornton Scale respectively. Severity of ADRs was assessed by Modified Hartwig and Siegel Scale.Results:Totally 288 ADRs were reported in a 2-year period. 92.01% ADRs were non serious. 44.8% were mild, 53.81% moderate and 1.39% were severe ADRs. Causality assessment showed: 5.21% certain, 54.86% probable, 39.24% possible and 0.69% unlikely ADRs. Around 26% ADRs were definitely and probably preventable and 27.78% ADRs were predictable. The highest number (32.29%) of ADRs were reported to antimicrobials. 11.15% ADRs were reported to NSAIDs, in that 37.5% ADRs were due to NSAIDs combination.Conclusion:Many ADRs in this study are non-serious, preventable and predictable. Management of such ADRs through therapeutic interventions would be beneficial in a better patient outcome. Multidisciplinary strategies involving physicians, pharmacists, other healthcare professionals and patient education and awareness about ADRs are needed for prevention of ADRs.

P-198 Prevalence of deleterious DPYD variants in patients with gastrointestinal malignancies: Real-world data from a single institution in Italy

Fluoropyrimidine (FP) represents a cornerstone in the treatment of gastrointestinal (GI) malignancies. Severe adverse drug reaction (ADR) may occur in 10% to 30% of patients treated with FP. Dihydropyrimidine dehydrogenase (DPYD) is a polymorphic gene encoding for DPD, involved in FP catabolism. The identification of variants associated with deleterious enzyme activity and increased risk of toxicity is recommended before treatment initiation [c.1905+1G>A(*2A); c.1679T>G(*13); c.1129-5923C>G, c.1236G>A(HapB3); c.2846A>T) or during treatment in case of ADR [c.2194G>A (*6)]. The estimated prevalence of DPYD deficient genotypes in the European population is < 8%. We aimed at determining the prevalence of DPYD deficient gene variants in a cohort of patients with GI malignancies treated at our department. A consecutive series of patients diagnosed with GI malignancies at our department from 15th June 2020 to 15th March 2021 and candidate to a FP-based therapy was assessed for germline DPYD testing before treatment initiation. The following variants were examined: c.1905+1G>A(*2A); c.1679T>G(*13); c.1129-5923C>G, c.1236G>A(HapB3); c.2846A>T; c.2194G>A(*6). The analysis included 310 patients, of which 226 with colorectal [CRC], 37 gastro-esophageal [GEC], 36 biliopancreatic [BPC], 7 other GI cancer (i.e. anal, NET), and 2 with double-tumor diagnosis (CRC/GEC, GEC/BPC). Overall, 261 patients (84%) were DPYD wild-type (WT) and 49 (16%) were carriers of a deleterious DPYD variant. Among positive cases, 39 (80%) had CRC, 5 BPC (10%), 3 GEC (6%), 1 other GI tumor-type (2%) and 1 had a second GI cancer (CRC/GEC) (2%). No association was observed between DPYD status and tumor-type (p=0.48). Out of 310 patients, 50 deleterious variants were observed in 49 patients: c.2194G>A(*6) in 37 cases (12%), of which one homozygous; c.1905+1G>A(*2A) in 6 (2%); c.1129-5923C>G in 4 (1%); c.2846A>T in 2 ( G(*13) in 1 ( In patients carrier of a deleterious variant, in 35 cases (11%) the recommended total dose (TD) of FP was 85%, in 10 (3%) was 50%, in 4 ranged from 50% to 75% (1%), whereas no variation in the TD was recommended (TD 100%) in WT cases (N=261, 84%). Of interest, of 54 patients enrolled in interventional phase II or III clinical trials including FP treatment, 6 patients (12%) displayed a gene variant requiring a FP-dose reduction. In our cohort, the prevalence of DPYD deleterious variants was more frequent than in reported data. DPYD*6 c.2194G>A was the most frequent genotype requiring a dose adjustment. No correlation between DPYD variants and tumor type was observed. According to our data, the assessment of deleterious DPYD variants and consequent FP-dose adjustment should be included in clinical trials protocols including FP treatment in order to prevent ADR and to adequately report toxicity profile and changes in patients' quality of life.

Thyroid Profile and Factors Associated with Hypothyroidism Among Multidrug-Resistant Tuberculosis Patients Attending Saint Peter's Specialized Hospital Addis Ababa, Ethiopia.

BackgroundThe emergence of MDR-TB is a global public health problem. Hypothyroidism is one of the severe adverse drug reactions (ADRs) in MDR-TB patients on treatment. Representative data on hypothyroidism and its associated factors among MDR-TB patients are lacking.ObjectiveTo determine thyroid profiles and associated risk factors among multidrug-resistant TB patients during therapy with anti-MDR-TB regimen in Saint Peter Specialized Hospital Addis Ababa, Ethiopia from January to November 2020.MethodsA cross-sectional study was conducted in MDR-TB patients in Addis Ababa, Ethiopia. A total of 162 patients, who were older than 18 years, had bacteriologically confirmed MDR-TB and on treatment for more than one month were enrolled consecutively from the TB registration book. However, critically sick patients and those who were receiving additional drugs known to cause severe ADRs were excluded. Simple descriptive statistics were used to present the socio-demographic and clinical characteristics of the patients. A logistic regression model was used to assess the association between independent and dependent variables. A p-value <0.05 was considered as statistically significant in all analyses.ResultsMean age of the study participant was 35.9 ± 13.6 years. The prevalence of hypothyroidism was 32 (19.8%). The presence of co-morbidity, being underweight, and prothionamide use were significantly associated with hypothyroidism in MDR-TB patients on treatment.ConclusionHypothyroidism occurs commonly among MDR-TB patients. Presence of co-morbidity, being underweight, and prothionamide drug use are the factors associated with hypothyroidism. Monitoring of thyroid function test during MDR-TB treatment and factors associated with hypothyroidism require attention to prevent complication.