Characteristics Of Adverse Drug Reactions Research Articles

Characteristics of adverse drug reactions to N-acetylcysteine for paracetamol overdose in a tertiary Institution in Singapore

Characteristics of adverse drug reactions to N-acetylcysteine for paracetamol overdose in a tertiary Institution in Singapore

Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system

Objective Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. Methods Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. Results The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31–2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69–4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87–14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. Conclusions MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.

Characteristics of adverse drug reactions due to nonsteroidal anti-inflammatory drugs: a cross-sectional study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating pain and inflammation. Spontaneous adverse drug reaction (ADR) reports represent a rich data source for the detection of unknown and rare ADRs. This cross-sectional study aimed to analyze the characteristics of ADRs due to NSAIDs in Thailand. All ADR reports of NSAIDs for systemic use from 2015 to 2019 were extracted from the national database in Thailand. Patient characteristics, drug use information, adverse event information, and source of senders in 32,857 reports were analyzed. The annual number of ADR reports due to NSAIDs decreased from 7,008 in 2015 to 5,922 in 2019. The most frequently reported drug was ibuprofen (n=12,645, 38.5%) followed by diclofenac (n=7,795, 23.7%), most patients were 40-59 years old, and the major adverse reaction was angioedema (n=7,513, 22.9%). Serious reactions were recorded in 20.7% (n=6,801) of the total ADRs. Most patients (n=20,593, 62.7%) recovered without sequelae, but there were 5,420 patients (16.5%) who could not recover and 3,109 patients (9.5%) who were recovering. Eight patients (0.02%) died of Stevens-Johnson syndrome (n=3), toxic epidermal necrolysis (n=4), and anaphylactic shock (n=1), which were possibly related to ADRs. The number of ADR reports due to NSAIDs decreased from 2015 to 2019 in Thailand. Serious ADRs and death cases accounted for 20.7% and 0.02%, respectively. Most fatal cases exhibited severe drug-induced skin reactions.

Epidemiology of adverse drug reactions to antihypertensive, antithrombotic and antidiabetic medications among adult inpatients at a National Referral Hospital, Uganda

ABSTRACT Introduction Treatment for hypertension, thrombosis and type 2 diabetes mellitus is long term and usually requires a combination of drugs which increases the risk of adverse drug reactions (ADRs). This study aimed to establish the prevalence at admission, incidence during hospitalization and characteristics of ADRs linked to antihypertensive, antithrombotic and antidiabetic drugs among adult inpatients in Uganda. Methods We conducted a secondary analysis of data from a previously assembled prospective cohort study in Uganda’s Mulago National Referral Hospital. We reviewed the files of inpatients who received antihypertensive, antithrombotic and/or antidiabetic medications prior to and/or during hospitalization. The modified Schumock and Thornton Preventability Scale, the Division of AIDS Table for Grading the Severity of Adult and Paediatric Adverse Events and the World Health Organization – Uppsala Monitoring Centre seriousness criteria were used to characterize the ADRs. Results More than a quarter (27%, 42/155) of the inpatients experienced an ADR at admission or during hospitalization. The point prevalence of ADRs at admission was 8% (13/155) and the incidence of ADRs during hospitalization was 23% (36/155). Forty-one percent (35/86) of the ADRs were serious and the majority (59%, 51/86) were preventable. Conclusion One in 13 inpatients experienced an ADR on admission and one in four experienced an ADR that developed during hospitalization. Clinicians ought to prescribe medicines with lower ADR risk profile for cardiovascular and/or diabetic patients whenever possible.

Characteristics of adverse drug reactions induced by flutamide and bicalutamide: a real-world pharmacovigilance study using FAERS

ABSTRACT Background Flutamide and bicalutamide are indicated for the management of prostate metastatic carcinoma. The current study evaluated the adverse drug reactions related to flutamide and bicalutamide in a real-world setting. Methods To quantify the signals of flutamide and bicalutamide associated adverse events (AEs), we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study using established pharmacovigilance methods. Results A total of 2711 AEs of flutamide were investigated as the primary suspected; 522 AEs were related to prostate cancer. A total of 4459 AEs were investigated as the primary suspected for bicalutamide; 2251 AEs were related to prostate cancer. The analysis demonstrated 29 signals for flutamide and 84 for bicalutamide. Liver function test was the most common AEs for flutamide, and malignant neoplasm progression was the most common for bicalutamide. The signal strength of Dementia Alzheimer’s type was 26.53 (17.89–39.35) and 26.33 (607.34), which had the highest strength for flutamide. Anti-androgen withdrawal syndrome exhibited the strongest signal for bicalutamide. Generating awareness of rare AEs that were not listed on the label is critical. Conclusions The analysis of the AE signals may provide support for prescribing flutamide and bicalutamide.

Comparing patient reported and medical record data of adverse drug reactions to anti-seizure drugs.

Anti-seizure drugs (ASDs) can potentially cause serious adverse drug reactions (ADRs). Patient self-reporting can increase the rate of ADR detection, but studies examining patient self-reporting of ADRs caused by ASDs are lacking. To determine the characteristics of ADRs reported by patients receiving ASDs, assess laboratory data and medical record confirmation of patient-reported ADRs, and explore factors associated with laboratory data and medical record confirmation. A self-reporting questionnaire was distributed to patients prescribed ASDs at outpatient clinics. Patients assessed the causality of suspected ADRs using Causality Assessment Tool. Naranjo's algorithm was used by researchers for causality assessment. Medical records were used to gather information on ADR symptoms, ASD medication, and abnormal laboratory data. From 478 distributed questionnaires, 93.1% completed the questionnaire and 67.4% of respondents reported at least one ADR. The most common ADRs were drowsiness (50.7%), dizziness (9.7%), and ataxia (4.3%). For causality, suspected ADRs were classified as possible in 52.3% of cases and probable in 46.3% of cases by patients, and possible in 64.7% of cases and probable in 25.7% of cases by researchers. Only 12.7% of patients had laboratory data and/or medical record confirmation of suspected ADRs. The psychiatry clinic was less likely to confirm suspected ADRs compared to the epilepsy clinic (OR = 0.412, p = 0.022). Confirmation of patient-reported ADRs with either laboratory data or medical records was uncommon. Recording patient-reported ADRs in patients' medical history and monitoring laboratory tests related to patient-reported symptoms should be promoted to increase the safety of ASD treatment.

Cannabinoid-based medicines in clinical care of chronic non-cancer pain: an analysis of pain mechanism and cannabinoid profile

Aim: Among treatments for chronic non-cancer pain (CNCP), cannabinoid-based medicines (CBMs) have become extremely popular. Evidence remains modest and limited primarily to delta-9-tetrahydrocannabinol (THC) for neuropathic pain; nevertheless, the use of various CBMs, including cannabidiol (CBD) to treat neuropathic, nociceptive, and mixed pain has increased globally. This observational case-series assessed the impact of CBMs as a complementary treatment by pain mechanism and cannabinoid profile over three months. Methods: An analysis of patients with CNCP and treated with CBMs who consented to an ongoing registry was performed. Outcomes were patient-reported such as the Edmonton symptom assessment system-revised, brief pain inventory-short form, and 36-item short form health survey. Data from patients with complete outcomes for baseline and 3-month follow-up was extracted. Characteristics of adverse drug reactions (ADRs), including a description of the suspected product were also assessed. Results: A total of 495 patients were part of this analysis (mean age = 56 years old; 67% women). At 3-month, the proportional use of THC:CBD balanced and THC-dominant products increased. Patients with neuropathic pain had higher pain-severity scores vs. nociceptive pain. In addition to patients with neuropathic pain, patients with nociceptive and mixed pain also reported improvements in pain severity and secondary symptoms such as anxiety, depression, drowsiness, fatigue, sleep disturbances, and overall, health-related quality of life. THC-dominant treatment is more likely to be recommended when pain is severe, whereas CBD-dominant is favored for less severe cases. ADRs were more frequent among cannabis-naive patients and included dizziness, headache, and somnolence among others. Conclusions: Findings suggest that CBMs can be effective for neuropathic as well as nociceptive and mixed pain. THC is more frequently recommended for neuropathic and severe pain. Future research on CBMs in pain management must include details of CBM composition, and pain mechanism and must consider potential ADRs.

Adverse drug reactions in neonatal intensive care unit: Characteristics and risk factors

Adverse drug reactions (ADRs) in neonates can significantly affect expected clinical outcomes. The aim of this study was to analyze the prevalence and characteristics of ADRs and identify the risk factors involved in a neonatal intensive care unit (NICU). A prospective cohort study based on intensive pharmacovigilance was carried out in NICU of a public teaching hospital in the south of Mexico. Neonates admitted to the NICU who had between 1 and 90 days of age, with at least 24 hours of hospitalization, and a confirmed suspicion of ADRs were included. The prevalence and characteristics of ADRs were analyzed. Relative ratios (RR) were estimated with 95% confidence intervals (CI) to evaluate the risk factors of ADRs (p˂0.05). 998 newborns were included, 109 ADRs were detected in 75 newborns, the cumulative incidence was 7.51% and the ADRs were mainly probable imputability and moderate severity. The therapeutic group most frequently related to the development of ADRs was anti-infectives for systemic use and the blood and lymphatic system was most affected by the ADRs. Identified risk factors were: female sex (RR 1.58; 95% CI 1.01-2.47), prematurity (RR 5.6; 95% CI 3.45-9.11), low birth weight (RR 2.52; 95% CI 1.63-3.91), length of hospitalization &gt;15 days (RR 12.95; 95% CI 7.89-21.25) and drugs administered &gt;5 (RR 5.92; 95% CI 2.6-13.48). These results should be considered and studied in greater depth, which will allow the prevention of the development of ADRs in this group of patients.

Pattern of adverse drug reactions reported at the adverse drug reaction monitoring centre at tertiary care teaching hospital in North India

Background: The aim of the present study was to determine the pattern of adverse drug reactions (ADRs) reported at ADR monitoring centre (AMC) in Punjab. Methods: This observational retrospective study was done in department of Pharmacology, GGS Medical College and Hospital, Faridkot from September 2020 to August 2021. A total of 148 ADRs were reported during the study period. Each ADR was analyzed for demographic data and characteristics of ADR. Assessment of causality, severity and preventability was done according to WHO UMC scale, modified Hartwig and Siegel scale and Modified Schumock and Thornton Preventability Scale respectively. Results: A total of 148 ADRs were reported from both outpatients and in patients of various departments. Most of the ADRs were found in males (55%) and patients of age group 31-45 years (33%). Majority of ADRs were reported from dermatology department (40%). Overall, 38% of ADRs were due to antimicrobial drugs. Most of the ADRs were reported as possible (57%), followed by probable (41%) as per WHO causality assessment. Most of the ADRs were moderate severity (83%). 97% of the ADRs were found to be definitely preventable type. Conclusions: We concluded that most of the ADRs were reported from antimicrobial drugs, so it is advisable to have close monitoring of the antimicrobial drug therapy to prevent ADRs in the patients. Although the majority of ADRs were moderate in nature but mostly were recovered. The study of ADRs in a particular institute using demographic patterns will contribute to patient safety by sensitizing the clinicians in that particular institute.

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.

Patient involvement in pharmacovigilance: determinants and evolution of reporting from 2011 to 2020 in France

IntroductionBecause patients and patient organizations want to strengthen their role in the care pathway and drug evaluation and in order to improve pharmacovigilance activities, European competent authorities implemented regulations to allow direct reporting of adverse drug reactions related to medicinal products by patients in 2012.ObjectivesTo describe evolution and analyze determinants of patient reporting activity in France in order to assess patient involvement in pharmacovigilance.MethodUsing the French national pharmacovigilance database, univariate and multivariate analyses were performed to compare the characteristics of adverse drug reaction (ADR) reports from patients and healthcare professionals (HCP) between 2011 and 2020. The relationship between regional patient ADR report activity and regional care provision and socio-professional characteristics was analyzed using the principal component analysis.ResultsA significant and higher increase in ADR reports over time from patients (r = 0.89, p < 0.001) compared to HCP (r = 0.27, p = 0.002) has been observed. Patient ADR report activities compared to HCP concerned more women (80% vs. 55%, p < 0.001), younger age classes (p < 0.001), reporting through web portal (83% vs. 17%, p < 0.001), and less serious events (26% vs. 63%, p < 0.001). In the principal component analysis, regional patient reporting activity was related to socio-professional categories, age classes, and densities of hospital beds and physicians.ConclusionOur results confirm an increasing involvement of patients in ADR report activities. The determinants of patient reporting activities are not only related to drug and medical factors but also to social factors. Digital tools may also play a role in health democracy in pharmacovigilance.

Analysis of burden and outcomes of anti-tuberculosis therapy-induced adverse drug effects at a tertiary care center

Background: Tuberculosis (TB), one of the most ancient diseases known to mankind, is one of the ten major causes of mortality worldwide. Combinations of antibiotics, called anti-TB therapy (ATT), are given for a period of six months or more as treatment. Aims and Objectives: The aim of this study was to assess the incidence of adverse drug reactions (ADRs), clinical profile, severity and causality among the admitted patients taking ATT in a tertiary care hospital. Materials and Methods: This was a hospital-based, prospective, observational and non-interventional cohort study undertaken in the General Medicine wards of the hospital. This study was conducted from June 2017 to December 2018. The Patients’ data was recorded using a structured ADR reporting form. The baseline parameters, medical history and details of underlying diseases, clinical data, characteristics of ADRs and details of medication responsible for ADRs as well as medication for treatment of ADRs were recorded. The data was analyzed using descriptive statistics with the Statistical Packages for the Social Sciences (SPSS) version 26.0 software. Results: Out of the 164 patients admitted due to ADRs within the study period, 45 (27.4%) developed ADRs due to anti-TB treatment. Most ATT-related ADRs involved the liver (n=39). The severity of ADR was found to be mild in two patients (4.4%), moderate in 28 patients (62.5%) and severe in 15 patients (33.3%). 16 patients (35.6%) completely recovered, 23 patients (51.1%) were still recovering (at the time of the analysis of the data), one patient (2.2%) did not recover and five patients (11.1%) had a fatal outcome. The presence of systemic comorbidities and polypharmacy was found to be a significant risk factor associated with ATT associated ADRs. Conclusion: ATT is not without its side effects. About 27.4% of the patients on ATT in our study developed ADRs, a few resulting in fatality. Educating the patients about possible ADRs associated with ATT at the time of prescription can improve patient compliance and strengthen the doctor-patient relationship. Early diagnosis and treatment of ADRs associated with ATT is paramount. This requires a better surveillance system, which India is in a dire need for.

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis.

Immune checkpoint inhibitors (ICIs) combined with the anti-angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large-scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan-cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan-cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14-12.10, P < .0001), hypertension (OR: 1.35; 95% CI: 1.11-1.65, P < .01) and gastrointestinal bleeding (OR: 3.16; 95% CI: 2.21-4.51, P < .0001). A subgroup analysis revealed that the risk of endocrine system-related ADRs was elevated in patients receiving different combination therapies or with certain tumor types. We retrospectively studied the ADR of combination therapy in Pan-cancer patients and analyzed the distribution characteristics of ADR from the perspectives of treatment strategy and cancer types to provide recommendations for the individualized management of patients receiving combination therapy.

Rho-associated coiled-coil kinase contributes an important role in Xingnaojing injection-induced adverse drug reactions

Xingnaojing injection (XNJI) is widely used for acute cerebral hemorrhage. However, the adverse drug reactions (ADRs) caused by XNJI have attracted broad attention. In this study, mice were intravenously administrated with a single dose of XNJI (10 or 20 mL/kg) to evaluate the vascular permeability. Then, pathological examinations on ears and lungs were performed to further determine the characteristics of ADRs induced by XNJI. In addition, human umbilical vein endothelial cells (HUVECs) were stimulated with XNJI (1/128, 1/64, and 1/32 XNJI pure product dilution) and stained with rhodamine-phalloidin to analyze the alterations on cytoskeleton. In addition, endothelial monolayer was incubated with XNJI and the effect on permeability was tested. Western blot testing was conducted to measure the involvement of Rho-associated coiled-coil kinase (ROCK) in XNJI-induced ADRs and fasudil hydrochloride was applied to additionally confirm the contribution of ROCK. The results indicated that XNJI may lead to dose-associated vascular leakage. None visibly abnormal symptom was noticed in the mice treated with XNJI at 10 mL/kg, while inflammation in ears and lungs was observed in the mice administrated with 20 mL/kg XNJI. In in vitro experiment, stimulation with high concentration of XNJI (1/32 XNJI pure product dilution) could enhance the permeability of confluent endothelial monolayer and induce rearrangement of actin cytoskeleton. Activation of ROCK, which was shown as augmented expressions of p-MLC2 and p-MYPT1, was observed in cells and mice treated with XNJI. ROCK inhibitor could attenuate XNJI-induced dysfunction of endothelial barrier in in vitro experiment and alleviate the vascular leakage and inflammation noticed in mice treated with XNJI. This study indicates that overdose of XNJI can destroy vascular endothelial function and induce increased vascular permeability, which may cause ADRs in clinical practice. Meanwhile, ROCK plays an important role in XNJI-induced ADRs.

Incidence and characteristics of adverse drug reactions in a cohort of patients treated with PD-1/PD-L1 inhibitors in real-world practice.

BackgroundData related to adverse drug reactions (ADRs), specifically immune-related adverse events (irAEs), in long-term treatment with immunotherapy in real-world practice is scarce, as is general information regarding the management of ADRs.ObjectivesTo characterize and describe the incidence of ADRs in patients who began immunotherapy treatment in clinical practice.MethodsIn a prospective observational study cancer patients ≥18 years of age who were treated with a monotherapy regime of PD-1/PD-L1 inhibitors were evaluated. The study period was from November 2017 to June 2019 and patients were followed up until June 2021. Patients were contacted monthly by telephone and their electronic health records were reviewed. Each ADR was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).ResultsOut of 99 patients, 86 met the inclusion criteria. Most were male (67.4%), with a median age of 66 (interquartile range, IQR: 59–76). The most frequent cancer was non-small cellular lung cancer (46 cases, 53.5%), followed by melanoma (22, 25.6%). A total of 74 patients (86%) were treated with anti-PD-1 drugs and 12 (14%) were treated with anti-PD-L1 drugs. The median treatment durations were 4.9 (IQR: 1.9–17.0) and 5.9 months (IQR: 1.2–12.3), respectively. Sixty-three patients (73%) developed from a total of 156 (44% of the total number of ADR) irADRs, wherein the most frequent were skin disorders (50 cases, 32%, incidence = 30.5 irADRs/100 patients per year [p-y]), gastrointestinal disorders (29, 19%, 17.7 irADRs/100 p-y), musculoskeletal disorders (17, 11%, 10.4 irADRs/100 p-y), and endocrine disorders (14, 9%, 8.6 irADRs/100 p-y). A total of 22 irADRs (14%) had a latency period of ≥12 months. Twelve irADRs (7.7%) were categorized as grade 3–4, and while 2 (1.3%) were categorized as grade 5 (death). Sixty-one irADRs (39.1%) in 36 patients required pharmacological treatment and 47 irADRs (30.1%) in 22 patients required treatment with corticosteriods.ConclusionThe majority of patients treated with anti-PD1/PDL1-based immunotherapy experienced adverse reactions. Although most of these reactions were mild, 11.5% were categorized as grade 3 or above. A high percentage of the reactions were immune-related and occurred throughout the treatment, thereby indicating that early identification and close monitoring is essential.

The importance of a World Health Organization international pharmacovigilance database (VigiBase): novel methods for safety monitoring and surveillance of medical products

Pharmacovigilance and medical product safety issues are important for all global citizens. Previous studies have analyzed the disaster caused by thalidomide in 1961. In 1963, the 16th World Health Assembly was determined to create the World Health Organization (WHO) Pilot Research Project for International Drug Monitoring in order to develop and understand adverse effects of medical products. In 1968, this pilot research project developed into the WHO Programme for International drug Monitoring (earlier versions of VigiBase) coordinated by the Uppsala Monitoring Center (Uppsala, Sweden) which expanded in scale to include 153 member countries, 22 associates, and many regional reporting centers as of March 2022. The main goal of the WHO Global ICSR Database System (VigiBase) is detecting, understanding, assessing, and preventing adverse effects of medical products (herbals, complementary medicines, biologic products, blood products, medical devices, and vaccines). This article aims to provide appropriate and strong reference of adverse reactions in specific drugs and novel method to identify specific features of adverse drug reactions through data and information achieved by VigiBase.

Analysis of adverse drug reactions of Osimertinib in the 2nd‐line treatment of EGFR mutant advanced nonsmall cell lung cancer

The aim was to analyze the clinical characteristics of adverse drug reactions (ADRs) induced by Osimertinib and their effects on the prognosis, so as to further provide reference for clinical medication. This was a retrospective study, and 66 nonsmall cell lung cancer (NSCLC) patients who had ADR in the 2nd-line treatment with Osimertinib from January 2017 to December 2018 were included. Clinical characteristics and survival in subgroups of Osimertinib-related ADRs were analyzed. The majority of patients who developed ADRs after the 2nd-line treatment of Osimertinib were mainly middle-aged and elderly women. Osimertinib-related ADRs were mainly found in the skin, respiratory and digestive systems. The most common ADRs were rash (69.70%), diarrhea (66.67%), stomatitis (54.55%), and fatigue (51.52%). The degree of Osimertinib-related ADRs was tolerable. Only seven patients experienced grade 3 ADRs, all of which involved the skin system. Exactly 92.42% of patients had more than two adverse reactions. The median PFS was influenced by the type, quantity, and severity of Osimertinib-related ADRs. Osimertinib-related ADRs are closely related to the prognosis of patients so that more attention should be paid to monitoring the occurrence of ADRs in clinical use of Osimertinib, especially ADRs in the skin, respiratory system and digestive system.

Long-term methimazole therapy in Graves' hyperthyroidism and adverse reactions: a Danish multicenter study.

PurposeIn this prospective multicenter study with patients newly diagnosed with Graves’ hyperthyroidism (GH), we studied the timing and characteristics of adverse drug reactions in patients treated with anti-thyroid drugs (ATD) for up to 48 months.MethodsPatients with GH were treated with ATD until remission and hereafter with a low-dose regime to keep the patients in remission. The patients were followed with blood samples and recording of adverse events approximately every second month for the first 2 years and every third month for the following 2 years.ResultsWe included 208 patients and the patients were treated for a median of 22 (range: 0.5–49) months. Ten percent of the patients experienced adverse drug reactions and 75% of the cases occurred during the first 6 months. After 24 months, the methimazole dose was lowered to 5 mg/day, and after this time point, no further adverse drug reactions were recorded. Skin reactions were the most prominent reaction, comprising 68% of the registered reactions, and no hepatic and bonemarrow affection was recorded.ConclusionWith this study, we report the frequency, timing of occurrence, and characteristics of adverse drug reactions when treating GH with the ATD drug methimazole for up to 48 months. Long-term low-dose methimazole treatment can be a cost-effective and straightforward treatment option if adverse drug reactions such as severe hepatic and bone marrow affection are kept in mind.

Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review.

Introduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6–68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=96513, identifier CRD42018096513.

Analysis of Burden and Outcomes of Oral Hypoglycaemic Agent Induced Emergency Services at a Tertiary Care Centre

Introduction: Recent studies, both globally as well as in India, have depicted an alarming rise in the prevalence of diabetes mellitus. Oral Hypoglycaemic Agents (OHAs) are the most common drugs used in the treatment of type 2 diabetes mellitus. There are numerous established Adverse Drug Reactions (ADR) associated with their use, such as, hypoglycaemia, weight gain, gastrointestinal disturbance, lactic acidosis and fluid retention. Aim: To assess the incidence of ADRs, clinical profile, severity and causality among the admitted patients, taking OHAs, in a tertiary care hospital. Materials and Methods: This was a hospital-based, prospective, observational, non interventional cohort study undertaken the General Medicine Wards of a public teaching hospital, Seth GSMC and KEMH, Mumbai, Maharashtra, India. This study was conducted in the Department of Medicine from June 2017 to December 2018. The patient’s data was recorded using a structured ADR reporting form. The baseline parameters, medical history and underlying diseases, clinical data, characteristics of ADRs and details of medication responsible for ADRs as well as medication for treatment of ADRs were recorded. The data was analyzed using descriptive statistics with the Statistical Packages for the Social Sciences (SPSS) version 26.0 software. Results: Out of 164 patients admitted due to ADRs, within the study period, 48 (29.3%) patients had developed ADRs due to OHAs (sulfonyluyreas). The severity of ADRs of five patients fell under the moderate category (3 males in the age group of 61- 80 years and 2 females in the age group of 21-40 years), all of whom successfully recovered. The remaining 43 (89.6%) were associated with severe ADRs, 42 of which recovered and one was still under recovering (the time of analysis of data). Four patients had succumbed to the ADR while one reported further sequalae. Conclusion: Sulfonylurea-induced hypoglycaemia is the most common ADR seen in patients on treatment of type 2 diabetes mellitus. Presence of systemic co-morbidities and polypharmacy are significant risk factors associated with OHA-induced ADRs.