Severe Adverse Drug Events Research Articles

Adverse Events and Efficacy of Acetazolamide in Meniere's Disease in a Vertigo Outpatient Clinic: A Retrospective Study.

Background Acetazolamide, a carbonic anhydrase inhibitor, is used in the treatment of several otolaryngological conditions, including Meniere's disease (MD). Despite its efficacy in reducing vertigo attacks, it is associated with a high rate of adverse events such as sensory disturbances, electrolyte imbalances, and liver dysfunction. The primary objective of this study is to evaluate the efficacy of acetazolamide in reducing vertigo attacks in MD patients. The secondary objective is to determine the incidence and severity of adverse drug events associated with acetazolamide treatment in this patient population. Methodology The study subjects were 70 patients who visited the vertigo outpatient clinic of our department from March 2019 to July 2024 and were diagnosed with definite or probable MD. Results A total of 15 cases had a history of acetazolamide prescription, with doses ranging from 125 to 750 mg/day. In total, 12 (80%) patients had symptoms of numbness in hands, feet, or other parts of the body, which caused discontinuation of medication after the initial prescription in five cases. Hypokalemia with liver dysfunction and hypokalemia with an open fracture of the distal end of the right radius due to staggering were observed in one patient each. In both cases of hypokalemia, Chinese herbal medicines containing licorice were prescribed in combination. Overall, 11 (73%) cases had a decrease in vertigo attacks. Hearing thresholds did not recover significantly after the prescription. Conclusions Although acetazolamide is effective in preventing vertigo attacks of MD, the rate of adverse events is high. Detailed instructions, careful dosage adjustment, periodic assessment of symptoms, and blood examinations for electrolyte and liver function are required.

Antiretroviral adverse drug events reported among adult HIV patients in a Nigerian tertiary hospital: A retrospective study

Background: The use of Highly Active Antiretroviral Therapy (HAART) has changed HIV/AIDS from a near-certainly fatal illness to one that can be managed chronically. A significant constraint of HAART is the high prevalence of adverse drug events (ADE) among HIV patients taking them. Objectives: The study determined the frequency and severity of reported antiretroviral adverse events among HIV-infected adults (≥16 years) at the Institute of Human Virology (IHV) Clinic of Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria, within five years. Antiretroviral therapies implicated in the reported adverse drug events were also determined. Method: Information on reported ADEs was extracted from the NAFDAC Pharmacovigilance forms in the Pharmacovigilance section of the IHV Clinic Pharmacy. The severity of ADEs was classified using the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index for categorizing errors. Results: A hundred and nineteen (119) patients reported 161 ADEs within the 5-year study period (2017-2021). Most ADE reports came from females (74.53%) and patients 36-55 years old. Dizziness (31.1%), Rashes (14.3%), and Fatigue (13.0%) were prominent among all the ADE reports documented. TDF/3TC/EFV (57.8%) and AZT/3TC/NVP (11.8 %) combinations were the frequently implicated antiretroviral regimen. All the ADEs reported were mild (Category ‘E’). ADE reports appreciated in the second year and progressively declined afterwards. Conclusion: There is a need to improve the system for antiretroviral ADE reporting through sensitization and developing a specific tool that enhances ADE reports from patients and healthcare providers.

Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.

Effectiveness of Jena DM® Herbal Formulation as Complementary Therapy to Conventional Oral Hypoglycemic Agents in Type-2 Diabetes Mellitus: A Quasi-experimental Study.

There is vast preclinical evidence that indicates that extracts from several Artemisia plant species have significant antidiabetic benefits. However, clinical evidence is limited to this effect. We sought to evaluate the effectiveness ofJena DM® (anArtemisia annua-based poly-herbal formulation) on glycemic control (Hb A1C) and insulin metabolism (HOMA), when administered as a complementary therapy in type-2 diabetes mellitus (T2DM). This study was supported by a research grant (JRD005) from Jena Herbals (U) Ltd, which is a local herbal medicines manufacturing facility in Uganda. We conducted a 12-week quasi-experimental study, involving 118 patients under routine follow-up at a diabetes and endocrinology clinic. Random assignment to either conventional or experimental study groups was done using a random number generator (Microsoft Excel version 16.0). Participant sociodemographic and clinical data as well as whole blood samples (3-5 mL) were obtained at scheduled clinic visits. Medication adherence was assessed using the Hill-Bone Scale, and adverse drug events (ADEs) using the Naranjo causality and the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) scales. Group differences in glycemic control (HbA1C), fasting serum insulin (FSI) indices (% HOMA2-B, HOMA-IR), and other cardiometabolic parameters were assessed using independent samples t-test, and Pearson chi-square statistical tests were used. A p-value <0.05 was considered statistically significant. Ethical approvals were obtained before the study commencement. 12-week daily complementary therapy withJena DM® showed no significant effect on Hb A1C reduction (0.1 (95% CI: -0.56, 0.80) %;p=0.798); however, we observed a significant reduction in total body weight (2.0 (95% CI: 0.73, 3.28) kg;p=0.002). The overall frequency of self-reported ADEs including dizziness was significantly higher among patients that usedJena DM® (p=0.001).Epigastric pain was the most severe ADE necessitating clinical management. There was no significant difference in the homeostatic model assessment for insulin resistance (HOMA2-IR) between study groups. In contrast to a few studies that previously showed significanthypoglycemic effects ofArtemisia-basedextracts, this study did not show a statistically significant reduction on HbA1C during a 12-week complementary use ofJena DM® in patients withT2DM. Based on the findings of this study, future research should evaluate the long-term effects ofJena DM® on body weight, overall insulin metabolism, and the subsequent effect on glycemic control in T2DM.

Adverse Drug Event–Related Hospital Admissions among Australian Aged Care Residents: A Cross-Sectional Study

ObjectivesTo investigate the proportion, characteristics, causality, severity, preventability, and independently associated factors for adverse drug event (ADE)–related admissions in aged care residents admitted to the major public hospitals in Tasmania, Australia. DesignRetrospective cross-sectional study. Setting and ParticipantsResidential aged care facility (RACF) patients aged ≥65 years who had an unplanned admission to one of the 4 Tasmanian public hospitals between July 1, 2018, and June 30, 2021. MethodsWe accessed the medical records of RACF patients. The ADEs were initially identified via chart review and a trigger tool. Hospitalizations attributable to ADEs were then determined by expert consensus. The causality, preventability, and severity of each ADE admission were assessed using standard criteria. ResultsNinety-one residents (18.2%) of 500 randomly selected experienced potential ADE-related hospitalizations. ADEs were considered possible (n = 58, 64%) or definite/probable (n = 33, 36%). The most common ADEs were falls (n = 19, 21%), hypotension (n = 16, 18%), and confusion or delirium (n = 10, 11%). ADEs were frequently associated with renin-angiotensin system inhibitors (n = 43, 47.3%), opioids (n = 43, 47.3%), and diuretics (n = 40, 44%). Most ADEs were of moderate severity (n = 90, 99%) and considered not preventable (n = 60, 66%). Rheumatologic disease [odds ratio (OR) 1.89, 95% CI 1.09-3.30; P = .024] and previous adverse drug reaction (ADR) (OR 12.91, 95% CI 6.84-24.37; P < .001) were associated with ADE hospitalizations. Conclusions and ImplicationsThis study highlights that hospitalization for moderately severe ADEs is common among RACF residents. Opioids and antihypertensives were the common drug classes associated with harm. Rheumatologic disease (due to opioids) and previous ADR were identified as independently associated factors, which may warrant tailored interventions.

Serious adverse drug events associated with psychotropic treatment of bipolar or schizoaffective disorder: a 17-year follow-up on the LiSIE retrospective cohort study.

Mood stabilisers and other psychotropic drugs can lead to serious adverse drug events (ADEs). However, the incidence remains unknown. We aimed to (a) determine the incidence of serious ADEs in patients with bipolar or schizoaffective disorders, (b) explore the role of lithium exposure, and (c) describe the aetiology. This study is part of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Between 2001 and 2017, patients in the Swedish region of Norrbotten, with a diagnosis of bipolar or schizoaffective disorder, were screened for serious ADEs to psychotropic drugs, having resulted in critical, post-anaesthesia, or intensive care. We determined the incidence rate of serious ADEs/1,000 person-years (PY). In 1,521 patients, we identified 41 serious ADEs, yielding an incidence rate of 1.9 events per 1,000 PY. The incidence rate ratio (IRR) between ADEs with lithium present and causally implicated and ADEs without lithium exposure was significant at 2.59 (95% CI 1.20-5.51; p = 0.0094). The IRR of ADEs in patients <65 and ≥65 years was significant at 3.36 (95% CI 1.63-6.63; p = 0.0007). The most common ADEs were chronic lithium intoxication, oversedation, and cardiac/blood pressure-related events. Serious ADEs related to treatment of bipolar (BD) or schizoaffective disorder (SZD) were uncommon but not rare. Older individuals were particularly at risk. The risk was higher in individuals exposed to lithium. Serum lithium concentration should always be checked when patients present with new or unclear somatic symptoms. However, severe ADEs also occurred with other mood stabilisers and other psychotropic drugs.

A249 PARADOXICAL PSORIASIS FOLLOWING ANTI-TNFΑ THERAPY IN INFLAMMATORY BOWEL DISEASE AND ASSOCIATION WITH AN IL-23 RECEPTOR VARIANT: A PRELIMINARY REPORT

Abstract Background Patients with inflammatory bowel disease (IBD) who receive anti-tumor necrosis factor (TNF) α therapy are at risk of developing drug-related psoriatic skin lesions known as paradoxical psoriasis (PP). This is a severe unpredictable adverse drug event that often leads to discontinuation of anti-TNFα therapy. To date, there are no tools for identifying high-risk individuals. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP. Aims To evaluate the frequency of the IL23R variant (IL23R1142Gampersand:003EA) in anti-TNFα exposed IBD patients who develop PP versus those who do not. Clinical variables associated with PP development will also be assessed. Methods A case-control study is ongoing, including anti-TNFα-exposed adult IBD patients. Participants are divided based on the development of PP (cases n=11; controls n=48, identified to date, 500 additional patients will be screened). All participants were retrospectively genotyped for the occurrence of the IL23R1142Gampersand:003EA variant. Clinical variables and outcomes were assessed from the time of anti-TNFα exposure for at least one year of follow-up or to the time of anti-TNFα discontinuation. Results To date, we have included 59 adult IBD patients treated with infliximab or adalimumab. Eleven patients developed PP after a median duration of treatment of three months with anti-TNFα therapy. The most common presentations were guttate, plaque, and pustular psoriasis. Six patients had PP that involved 50% or more of their body surface area (BSA). Nine participants discontinued their anti-TNFα therapy due to PP. None of the cases had a personal or family history of psoriasis. PP patients were similar to controls with respect to age, sex, ethnicity, IBD type, disease duration, and concurrent immunomodulator use. The variant genotype occurred more frequently in PP patients compared to controls (54.5% vs. 4.2%, OR 27.6, 95%CI 4.3-145.4). Those with the variant genotype also had more extensive psoriasis compared to wildtypes (mean BSA 61% vs. 25%, p=0.045). Conclusions In this preliminary analysis, there was an increased frequency of the IL23R1142Gampersand:003EA variant in patients who developed PP compared to those who did not after anti-TNFα exposure. We did not identify any other clinical variables associated with development of PP. Interpretation of these results is limited by the small sample size. Completion of this study may help clarify the association between PP and the IL23R gene as well as other clinical risk factors implicated in PP development. Funding Agencies None

Polypharmacy and Elevated Risk of Severe Adverse Events in Older Adults Based on the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database.

Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population. We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis. We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults. The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms.

Monitoring foradverse drug events ofhigh-risk medications with a computerized clinical decision support system: a prospective cohort study.

Monitoring is recommended to prevent severe adverse drug events, but such examinations are often missed. To increase the number of monitoring that should be ordered for high-risk medications, we introduced a clinical decision support system (CDSS) that alerts and orders the monitoring for high-risk medications in an outpatient setting. We conducted a 2-year prospective cohort study at a tertiary care teaching hospital before (phase 1) and after (phase 2) the activation of a CDSS. The CDSS automatically provided alerts for liver function tests for vildagliptin, thyroid function tests for immune checkpoint inhibitors (ICIs) and multikinase inhibitors (MKIs), and a slit-lamp examination of the eyes for oral amiodarone when outpatients were prescribed the medications but not examined for a fixed period. The order of laboratory tests automatically appeared if alert was accepted. The alerts were hidden and did not appear on the display before activation of the CDSS. The outcomes were the number of prescriptions with alerts and examinations. During the study period, 330 patients in phase 1 and 307 patients in phase 2 were prescribed vildagliptin, 20 patients in phase 1 and 19 patients in phase 2 were prescribed ICIs or MKIs, and 72 patients in phase 1 and 66 patients in phase 2 were prescribed oral amiodarone. The baseline characteristics were similar between the phases. In patients prescribed vildagliptin, the proportion of alerts decreased significantly (38% vs 27%, P < 0.0001), and the proportion of examinations increased significantly (0.9% vs 4.0%, P < 0.0001) after activation of the CDSS. In patients prescribed ICIs or MKIs, the proportion of alerts decreased significantly (43% vs 11%, P < 0.0001), and the proportion of examinations increased numerically, but not significantly (2.6% vs 7.0%, P = 0.13). In patients prescribed oral amiodarone, the proportion of alerts decreased (86% vs 81%, P = 0.055), and the proportion of examinations increased (2.2% and 3.0%, P = 0.47); neither was significant. The CDSS has potential to increase the monitoring for high-risk medications. Our study also highlighted the limited acceptance rate of monitoring by CDSS. Further studies are needed to explore the generalizability to other medications and the cause of the limited acceptance rates among physicians.

Intralesional betamethasone versus oral propranolol for localized infantile hemangiomas of the lip

Infantile hemangiomas (IHs) of the lips are associated with an increased risk of incomplete involution and ulceration, causing disfigurement. Treatment with oral propranolol (OPT) has credible efficacy but takes months to complete. Thus, this study aimed to investigate the efficacy of intralesional betamethasone injection (IBI) as an alternative treatment for protruding localized IHs of the lips. To investigate the efficacies of OPT and IBI, we designed a prospective, noninferiority, parallel-group study. The primary outcome assessed was treatment response rate. Secondary outcome assessments included lesion size changes and surgical rate. Additionally, complication rates and treatment durations of OPT and IBI were compared. The treatment response rate of IBI was not inferior to that of OPT (95.7% vs. 76.0%, respectively; a difference of 19.7%, 95% confidence interval [CI], -4.4% to 41.6%). The average surgical rate in the IBI group was significantly lower than that in the OPT group (8.7% vs. 40%, respectively; p=0.012), and the average duration of treatment for IBI was shorter than that of OPT (2.1 months vs. 6.3 months, respectively; p<0.001). There were no severe adverse drug events in either group. If not managed properly, small, localized lip IHs may cause disfigurement in a child. Our study demonstrated that IBI is as effective as OPT in treating protruding localized lip IHs. Moreover, IBI treatment has a shorter duration and lower surgical rate than OPT. With proper care, IBI is an effective treatment modality for small and localized lip IHs.

Assessment of community pharmacists' knowledge about drug-drug interactions in Jeddah, Saudi Arabia.

Background: Drug-drug interactions (DDIs) have the potential to result in severe adverse drug events and profoundly affect patient outcomes. The pivotal role community pharmacists assume in recognizing and effectively managing these interactions necessitates a comprehensive understanding and heightened awareness of their implications. Such knowledge and awareness among community pharmacists are fundamental for ensuring the delivery of safe and efficacious care to patients. Aim: This study aimed to assess the knowledge of community pharmacists in Jeddah, Saudi Arabia, regarding drug-drug interactions (DDIs). Method: A cross-sectional survey was administered to a cohort of 147 community pharmacists through the utilization of a self-administered questionnaire. The questionnaire encompassed a comprehensive range of 30 multiple-choice questions, encompassing various facets pertaining to drug-drug interactions (DDIs). Results: A total of 147 community pharmacists working in Jeddah City, Saudi Arabia, completed the survey. The majority of them were male (89.1%, n = 131), and had bachelor's degrees in pharmacy. Results showed that the lowest correct response of DDIs was between Theophylline/Omeprazole, while the highest was between amoxicillin and acetaminophen. Results revealed that among the 28 drug pairs, only six pairs were determined correctly by most participants. The study found that majority of the studied community pharmacist could not determine the correct answer on drug-drug interaction knowledge, as also seen with the measured below half mean DDIs knowledge of 38.22 ± 22.0 (min = 0, max = 89.29, median = 35.71). Conclusion: The study highlights the need for ongoing training and education programs for community pharmacists in Saudi Arabia to enhance their knowledge and understanding of DDIs, ultimately leading to improved patient care and safety.

Predicting the Severity of Adverse Events on Osteoporosis Drugs Using Attribute Weighted Logistic Regression.

Osteoporosis is a serious bone disease that affects many people worldwide. Various drugs have been used to treat osteoporosis. However, these drugs may cause severe adverse events in patients. Adverse drug events are harmful reactions caused by drug usage and remain one of the leading causes of death in many countries. Predicting serious adverse drug reactions in the early stages can help save patients' lives and reduce healthcare costs. Classification methods are commonly used to predict the severity of adverse events. These methods usually assume independence among attributes, which may not be practical in real-world applications. In this paper, a new attribute weighted logistic regression is proposed to predict the severity of adverse drug events. Our method relaxes the assumption of independence among the attributes. An evaluation was performed on osteoporosis data obtained from the United States Food and Drug Administration databases. The results showed that our method achieved a higher recognition performance and outperformed baseline methods in predicting the severity of adverse drug events.

Use of complete medication history to identify and correct transitions-of-care medication errors at psychiatric hospital admission.

Methods for categorizing the scale and severity of medication errors corrected by pharmacy staff during admission medication reconciliation using complete medication history continue to evolve. We established a rating scale that is effective for generating error reports to health system quality leadership. These reports are needed to quantify the value of investment in transitions-of-care pharmacy staff. All medication errors that were reported by pharmacy staff in the admission medication reconciliation process during a period of 6 months were eligible for inclusion. Complete medication history data source was utilized by admitting providers and all pharmacist staff and a novel medication error scoring methodology was developed. This methodology included: medication error category, medication error type, potential medication error severity, and medication non-adherence. We determined that 82 medication errors were detected from 72 patients and assessed that 74 of these errors may have harmed patients if they were not corrected through pharmacist intervention. Most of these errors were dosage discrepancies and omissions. With hospital system budgets continually becoming leaner, it is important to measure the effectiveness and value of staff resources to optimize patient care. Pharmacists performing admission medication reconciliation can detect subtle medication discrepancies that may be overlooked by other clinician types. This methodology can serve as a foundation for error reporting and predicting the severity of adverse drug events.

Antibiotic Prescription Audits Among Pediatric Outpatients With Acute Ailments in a Secondary Care Hospital During the COVID-19 Omicron Wave in Northern India.

Background Antibiotics, as defined by the World Health Organization (WHO), are pharmaceuticals used to treat bacterial infections. There is growing recognition that inappropriate antibiotic prescription in children is linked to increasing rates of severe adverse drug events and higher medical expenditures. There are a few prescriptions audit studies from smaller cities in Northern India, especially those conducted during the COVID-19 pandemic whenthe unregulated private sector accounted for 90% of antibiotic sales and 75% of healthcare requirements. Thestudy objectiveswere to determine the rate of outpatient antibiotic prescription and adherence to WHO drug indicators in prescriptions to pediatric outpatients in private healthcare facilities in India. Methodology This cross-sectional survey was conducted over three months (January to March 2022) in the outpatient setting of a private pediatric hospital in Kanpur, a city having a population of nearly three million population located in the state of Uttar Pradesh in India. Prescriptions of children aged <10 years with a history of onset of complaint <14 days were included in this audit. Prescriptions were numbered;data were collected using a specially designed semistructured, pretested prescription audit checklist; and the recommended WHO indicators were also calculated. Data were entered using CSPro (U.S. Census Bureau, Washington, DC, USA) and analyzed using STATA 15 (StataCorp LLC, College Station, TX, USA). Results This study observed an antibiotic prescription rate of 65.75%, which was higher than the WHO-recommended value, which might indicate indiscriminate usage of antibiotics in the setting. Out of the 144 antibiotic medications prescribed, none were generic and all the antibiotics were prescribed presumptively. The most commonly prescribed medicines were cefpodoxime, azithromycin, and ofloxacin, which were primarily used to treat cough and stomach infections. Conclusions This antibiotic audit conducted in a private hospital outpatient setting in a city in Northern India during the Omicron wave of the COVID-19 pandemic found nongeneric, predominantly oral, presumptive antibiotic prescriptions in nearly two out of three young pediatric patients. Improvement in prescribing practices through regulation, monitoring, and antibiotic stewardship in low-resource settings is urgently warranted to curb the impending global pandemic of antimicrobial resistance.

Medicatiefouten met methotrexaat: casuïstiek en opportuniteiten door de bril van de ziekenhuisapotheker

Medication errors with methotrexate: new insights into an old drug Methotrexate (MTX) was first used in 1948 to treat childhood leukaemia. Nowadays, it is used for the treatment of inflammatory diseases, such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis and inflammatory bowel disease. MTX is a folic acid antagonist that binds dihydrofolate reductase and thereby inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. As an incontestable cornerstone in the treatment of RA, MTX should be started as soon as RA is diagnosed. The primary goal of the treatment is rapid and effective disease control to prevent long-term damage to the joints. For the treatment of patients with RA, the usual starting dose of MTX is 7.5-10 mg per week. Based on the clinical response, the dose could be increased to reach the optimal dose. The most common adverse drug events of MTX therapy are gastro-intestinal intolerance, haematological abnormalities, alopecia, hepatotoxicity and pulmonary toxicity. Overall, MTX is well tolerated. However, fatal cases of MTX intoxication have been reported in literature, mainly due to the daily intake and thus overdose of MTX. Despite the widespread experience with MTX, medication errors still occur with a risk of potentially severe adverse drug events. Clinical pharmacy interventions aim to detect these medication errors in inpatients. Based on a case series within a hospital population, the most common medication errors with MTX are presented. Subsequently, specific interventions to optimize medication safety with MTX therapy are described. The implementation of a specific chemotherapy module in the computerized physician order entry and clinical pharmacy interventions, such as medication reconciliation, the engagement of clinical pharmacists on hospital wards as part of the interdisciplinary team and prescription validation based on clinical rules, can contribute to a safer use of MTX.

COVID-19 impact on the prevalence of PIMS in elderly patients according to STOPP/ START criteria: a record base study

Background: Polypharmacy, contribute to an increased risk of adverse drug reaction morbidity, and mortality, and increases the length of hospital stay, hospital revisits and readmissions. We aimed to evaluate the prevalence and trends of polypharmacy and potentially inappropriate medications in elderly patients with version 2. STOPP/START criteria, and assess the severity of adverse drug events in patients with PIMs.Methods: This is a retrospective, record-based study of over-the-counter, and potentially inappropriate medications in the prescriptions of patients (&gt;60 years). PIMs have been identified and further investigated to determine any adverse effects. If harm occurred, the severity of an adverse effect was rated using a modified Hartwig and Siegel scale. The causality of the events was assessed by using Naranjo's scale.Results: Out of 583 patients polypharmacy and excessive polypharmacy were found in 36.0%, and 42.8% of pre-admission medications. The most common over-the-counter (OTC) drugs were hydrocortisone (39.86%), ranitidine (21.62%), bisacodyl (14.86%), and diphenhydramine (12.84%). A statistically significant positive correlation was seen between age and the number of drugs prescribed (r2=0.16), while a non-significant positive correlation was found between sex, length of stay (LOS), and the number of drugs prescribed (r2 =0.0002, r2 =0.001). Common PIMs related incidence reported include Insulin (regular) 31.25% (N=20), Trihexyphenidyl (THP) 18.75%, zolpidem 12.5%, acetylsalicylic acid 9.3%, pantoprazole 52 7.81%, furosemide 7.8%, hydrocortisone 6.25%, and glimepiride 6.25%. Total of 130 ADRs 50% were mild, 28.4% were moderate, and 21.5% were severe. Out of 130 incidents, 64.6% were preventable, 22.3% were probably preventable, and 13.0% were not preventable. A total of 50.0% recovered completely from the ADRs, 33.0% had been recovering, 12.3% recovered with a squeal, 2.3% could not recover and 2.3% had been fatal.Conclusions: The study shows high uses of OTC and PIMs and PGx in elderly patients; which encourage intent need to develop awareness and action plans.

A retrospective analysis of peri-operative medication errors from a low-middle income country

Identifying medication errors is one method of improving patient safety. Peri operative anesthetic management of patient includes polypharmacy and the steps followed prior to drug administration. Our objective was to identify, extract and analyze the medication errors (MEs) reported in our critical incident reporting system (CIRS) database over the last 15 years (2004–2018) and to review measures taken for improvement based on the reported errors. CIRS reported from 2004 to 2018 were identified, extracted, and analyzed using descriptive statistics and presented as frequencies and percentages. MEs were identified and entered on a data extraction form which included reporting year, patients age, surgical specialty, American Society of Anesthesiologist (ASA) status, time of incident, phase and type of anesthesia and drug handling, type of error, class of medicine, level of harm, severity of adverse drug event (ADE) and steps taken for improvement. Total MEs reported were 311, medication errors were reported, 163 (52%) errors occurred in ASA II and 90 (29%) ASA III patient, and 133 (43%) during induction. During administration phase 60% MEs occurred and 65% were due to human error. ADEs were found in 86 (28%) reports, 58 of which were significant, 23 serious and five life-threatening errors. The majority of errors involved neuromuscular blockers (32%) and opioids (13%). Sharing of CI and a lesson to be learnt e-mail, colour coded labels, change in medication trolley lay out, decrease in floor stock and high alert labels were the low-cost steps taken to reduce incidents. Medication errors were more frequent during administration. ADEs were occurred in 28% MEs.

DRUG-DRUG INTERACTIONS IN PSYCHIATRIC PATIENTS: IDENTIFYING HIGH-RISK COMBINATIONS AND MITIGATION STRATEGIES

Psychiatric patients are at a high risk of severe adverse drug events (ADEs) due to potential drug-drug interactions (DDIs). These interactions can worsen existing health conditions and complicate treatment outcomes. Objective: This study aimed to identify and evaluate the drug-drug interactions (DDIs) of psychoactive drugs among mental health patients and propose effective prevention measures. A retrospective study was conducted at the Department of Pharmacy, Lady Reading Hospital, Peshawar, from January 1, 2021, to July 31, 2021. The study included all psychiatric patients treated during this period. Medication records were re-examined to identify drug-drug interactions (DDIs) using reliable drug interaction databases. Adverse effects resulting from these interactions were documented. Statistical analysis assessed the frequency and severity of the identified DDIs. Mitigation strategies were developed based on the probability and clinical relevance of the interactions. These strategies included drug adjustments, regular monitoring of patients, and patient education aimed at reducing the risk of adverse effects. The major DDIs frequently occur with commonly used psychiatric medications such as antipsychotics, antidepressants, and mood stabilisers. Common adverse effects included sedation, cardiovascular complications, and increased risk of serotonin syndrome. Mitigation measures, such as drug adjustment, regular monitoring, and patient education, were suggested to reduce the risk of adverse effects. Psychiatric patients are predisposed to severe ADEs due to DDIs, which are often difficult to predict. Mitigation measures such as appropriate drug adjustments and patient education are essential to enhance patient safety and treatment outcomes.

Challenges and Future of Drug-Induced Liver Injury Research—Laboratory Tests

Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which is also a major cause of study cessation and market withdrawal during drug development. Since no acknowledged diagnostic tests are available, DILI diagnosis poses a major challenge both in clinical practice as well as in pharmacovigilance. Differentiation from other liver diseases and the identification of the causative agent in the case of polymedication are the main issues that clinicians and drug developers face in this regard. Thus, efforts have been made to establish diagnostic testing methods and biomarkers in order to safely diagnose DILI and ensure a distinguishment from alternative liver pathologies. This review provides an overview of the diagnostic methods used in differential diagnosis, especially with regards to autoimmune hepatitis (AIH) and drug-induced autoimmune hepatitis (DI-AIH), in vitro causality methods using individual blood samples, biomarkers for diagnosis and severity prediction, as well as experimental predictive models utilized in pre-clinical settings during drug development regimes.

508 Comparing effectiveness and safety of levetiracetam loading doses among patients with status epilepticus.

OBJECTIVES/GOALS: Our long-term goal is to improve the clinical outcomes of patients with status epilepticus through increasing the level of evidence surrounding guidelines. The specific objective of our proposed work is to compare the outcomes and adverse drug events between the Neurocritical Care and American Epilepsy Society levetiracetam dose recommendations. METHODS/STUDY POPULATION: This is a retrospective, single site, cohort study comparing outcomes of hospitalized patients with status epilepticus treated with levetiracetam bolus at the University of Kansas Health System. Patients outcomes will be compared based on levetiracetam bolus dose received. The primary outcome will be seizure reoccurrence within 24 hours. Secondary outcomes include number of additional anti-epileptic drugs administered, cumulative dose of benzodiazepines administered within 24 hours of levetiracetam bolus administration and incidence of adverse drug reactions. All study data will be extracted retrospectively from the EPIC chart review following patient list generation through the HERON i2b2 database query. RESULTS/ANTICIPATED RESULTS: Aim 1 will characterize levetiracetam dosing among patients admitted to the University of Kansas Medical Center for status epilepticus during routine clinical care. We hypothesize that given the inconsistency in dosing recommendations from various professional societies and drug references, we will observe inconsistent dosing of levetiracetam among those hospitalized due to status epilepticus.Aim 2 will evaluate effectiveness and safety across the various levetiracetam doses. We estimate that adherence to the higher weight-based dosing recommendations of the 2016 American Epilepsy Society guideline may result in improved outcomes with a similar frequency and severity of adverse drug events compared to lower/fixed-dose levetiracetam dose recommendation of the 2012 Neurocritical Care guideline. DISCUSSION/SIGNIFICANCE: Notable inconsistencies across the dosing recommendations for levetiracetam exist between the guidelines for treatment of status epilepticus and commonly used tertiary drug information databases. This variation in guidance may lead to differences in dosing and warrants further exploration to better support the management of status epilepticus.