Frequent Adverse Drug Reactions Research Articles

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.

Characteristics of drug safety alerts issued by the Spanish Medicines Agency.

Objectives: To describe the characteristics of safety alerts issued by the Spanish Medicines Agency (AEMPS) and the Spanish Pharmacovigilance System over a 7-year period and the regulatory actions they generated. Methods: A retrospective analysis was carried out of drug safety alerts published on the AEMPS website from 1 January 2013 to 31 December 2019. Alerts that were not drug-related or were addressed to patients rather than healthcare professionals were excluded. Results: During the study period, 126 safety alerts were issued, 12 of which were excluded because they were not related to drugs or were addressed to patients and 22 others were excluded as they were duplications of previous alerts. The remaining 92 alerts reported 147 adverse drug reactions (ADRs) involving 84 drugs. The most frequent source of information triggering a safety alert was spontaneous reporting (32.6%). Four alerts (4.3%) specifically addressed health issues related to children. ADRs were considered serious in 85.9% of the alerts. The most frequent ADRs were hepatitis (seven alerts) and congenital malformations (five alerts), and the most frequent drug classes were antineoplastic and immunomodulating agents (23%). Regarding the drugs involved, 22 (26.2%) were "under additional monitoring." Regulatory actions induced changes in the Summary of Product Characteristics in 44.6% of alerts, and in eight cases (8.7%), the alert led to withdrawal from the market of medicines with an unfavorable benefit/risk ratio. Conclusion: This study provides an overview of drug safety alerts issued by the Spanish Medicines Agency over a 7-year period and highlights the contribution of spontaneous reporting of ADRs and the need to assess safety throughout the lifecycle of medicines.

Safety of antituberculosis agents used for multidrug-resistant tuberculosis among patients attending the Jamot Hospital of Yaounde, Cameroon.

Recognized in 1994 as a global emergency by the World Health Organization, tuberculosis (TB) remains an ongoing health threat. In Cameroon, the mortality rate is estimated at 2.9%. Treatment of multidrug-resistant TB (MDR-TB) defined as the resistance to the two most effective antiTB drugs, and requires therapy of more than 7 drugs taken on a daily basis during 9-12 months. This study aimed to evaluate the safety profile of treatment regimens used for MDR-TB at Jamot Hospital of Yaounde (JHY). This was a retrospective cohort study of patients treated for MDR-TB at HJY from January 1, 2017, to December 31, 2019. Patients characteristics of the cohort, drugs regimen were collected and described. All possible adverse drug reactions (ADR) were described clinically and by severity grade. During the study period, 107 patients were included, and 96 (89.7%) experienced at least one ADR. Most parts of the patients (90) experienced mild or moderate ADR. Hearing loss was the most frequent ADR, and led mostly in aminoglycosides dose reduction (n = 30, 96.7%). Gastrointestinal events were commonly observed during the study period. Our findings suggested that ototoxicity was a prominent safety issue during the study period. The implementation of the new short treatment regimen could be effective in reducing the burden of ototoxicity among MDR-TB patients. Nevertheless, new safety issues could emerge.

Artículo traducido] Prevalencia de reacciones adversas a medicamentos asociadas a visitas al servicio de urgencias y factores de riesgo de hospitalización

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the ED and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24; 95% CI: 1.47-7.13; p=0.003, in Charlson comorbidity index 4-6, and aOR 20.07; 95% CI: 6.87–58.64; p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

Prevalence of adverse drug reactions associated with emergency department visits and risk factors for hospitalization

ObjectiveAdverse drug reactions increase morbidity and mortality, prolong hospital stay and increase healthcare costs. The primary objective of this study was to determine the prevalence of emergency department visits for adverse drug reactions and to describe their characteristics. The secondary objective was to determine the predictor variables of hospitalization for adverse drug reactions associated with emergency department visits. MethodsObservational and retrospective study of adverse drug reactions registered in an emergency department, carried out from November 15th to December 15th, 2021. The demographic and clinical characteristics of the patients, the drugs involved and the adverse drug reactions were described. Logistic regression was performed to identify factors related to hospitalization for adverse drug reactions. Results10,799 patients visited the emergency department and 216 (2%) patients with adverse drug reactions were included. The mean age was 70 ± 17.5 (18-98) years and 47.7% of the patients were male. A total of 54.6% of patients required hospitalization and 1.6% died from adverse drug reactions. The total number of drugs involved was 315 with 149 different drugs. The pharmacological group corresponding to the nervous system constituted the most representative group (n = 81). High-risk medications, such as antithrombotic agents (n = 53), were the subgroup of medications that caused the most emergency department visits and hospitalization. Acenocumarol (n = 20) was the main drug involved. Gastrointestinal (n = 62) disorders were the most common. Diarrhea (n = 16) was the most frequent adverse drug reaction, while gastrointestinal bleeding (n = 13) caused the highest number of hospitalizations. Charlson comorbidity index behaved as an independent risk factor for hospitalization (aOR 3.24, 95% CI: 1.47–7.13, p = 0.003, in Charlson comorbidity index 4–6; and aOR 20.07, 95% CI: 6.87–58.64, p = 0.000, in Charlson comorbidity index ≥ 10). ConclusionsThe prevalence of emergency department visits for adverse drug reactions continues to be a non-negligible health problem. High-risk drugs such as antithrombotic agents were the main therapeutic subgroup involved. Charlson comorbidity index was an independent factor in hospitalization, while gastrointestinal bleeding was the adverse drug reaction with the highest number of hospital admissions.

Assessment of safety and adverse drug reactions of COVID vaccination in the South Indian population: An observational prospective cross-sectional study.

COVID vaccination is now offering a way to transit out of this phase of the pandemic. Two vaccines were approved by the Central Drugs Standard Control Organization (CDSCO) in India: Covishield and Covaxin. However, the vaccines are known to have Adverse Drug Reactions (ADRs) like fever, body pains, headache, pain, and swelling at the injection site. To assess the Safety of ADRs with Covid Vaccination in the South Indian Population. This prospective, multi-centric study was carried out for six months (February 2021-July 2021). Subjects vaccinated against COVID were enrolled in the study. Informed consent was taken from the study participants, and required data (age, gender, type of vaccine, and ADRs) was collected through telephonic interviews. The data were analyzed by using the Chi-square test. A total of 3032 participants were enrolled in the study. The prevalence of ADRs is highly observed after the 2nd dose (51%) of COVID vaccination. ADRs were mainly experienced by females (55%) than males (45%). The incidence of fever and body pains was high in Covishield after dose one and Covaxin after dose 2. The pain at the injection site was high in Covaxin after dose 2. The WHO assessment scale and Naranjo's scale shows that ADRs are higher likely than probable. We concluded that frequent ADRs that occurred with Covaxin and Covishield were fever, body pains, weakness, headache, and pain at the injection site. All the ADRs were mild and manageable with Paracetamol. So, the vaccines are safe to administer.

Adverse Drug Reaction Monitoring in Multidrug-Resistant Tuberculosis Patients Receiving Bedaquiline and Delamanid-Based Regimen.

Background and objectives Tuberculosis (TB) is an airborne contagious illness caused byMycobacterium tuberculosis.Ineffective anti-TB medication prolongs and exasperates illness, promotes disease spread,increases the probability of developing resistance to treatment, and increases death rate.Bedaquiline (BDQ) and Delamanid (DLM) were conditionally made available in the treatment of multidrug-resistant TB (MDR TB).In drug-resistantTB patients, adverse drug reactions (ADR) management is essential to improve medicationcompliance. In addition, we performed this study since there are very few studies published on the analysis ofADR monitoring of BDQ and DLM-based regimen. This study was performed tostudy the spectrum of ADR in drug-resistant TB patients receiving BDQ andDLM-based regimen. Methodology The study was conducted over a period of 26 months, in a hospital's departments of pharmacology and pulmonary medicine.Pre-extensively drug-resistant (Pre-XDR) and XDR TBwere established on the basis of cartridge-based nucleic acid amplification (CB-NAAT), line probe assay (LPA), drug susceptibility testing (DST), and bacteriological culture. Patients were prescribed with appropriate medicines at the initial visit and any adverse reactions to medication were assessed in the subsequent visit. The statistical analysis was done using frequency distribution procedure, chi-square test of independence. The significance level was set at p<0.05. Results It was revealed that there were as many as 24 types of ADRs manifested in different patients.The most frequent ADR was QTcF (corrected heart rate) prolongation. Conclusion The maximum number of patients had some form of ADR and the percentage was slightly higher in the BDQ group than in the DLM group.

Continuing Somatostatin Does Not Prevent Rebleeding After Variceal Ligation For Acute Variceal Bleeding

Background: variceal bleeding (VB) is a medical emergency. Endoscopic variceal ligation (EVL) performed quickly is beneficial. Evenafter EVL, somatostatin is still utilized in the VB band for 2–5 days. The advantage of continuing somatostatin after EVL is uncertainsince EVL is the main method for achieving hemostasis.Aim and objectives: to determine if continuing somatostatin after EVL is effective in reducing mortality and rebleeding.Subjects and methods: In this study, 75 patients with variceal bleeding were divided into two treatment groups (TG); TG2 &amp; TG5,which received somatostatin (250 micrograme bolus + a continuous infusion of 500 micrograme/h) for two days and five days,respectively, and one control group (TG0), which received 0.9 percent normal saline and was monitored for six weeks.Result: There were a total of 8 rebleeds; they happened more often in the TG0 (4%) and TG2 (2.6%) and TG5 (4%) groups, albeit notstatistically significantly (P=0.751). The treatment group substantially experienced more adverse drug reactions (ADRs) than the controlgroup (P=0.003). Diarrhoea was the most frequent ADR, followed by hyperglycemia and bradycardia, with 14 patients mentioning twoor more ADR. In comparison to the control group, ADR was considerably greater in the treatment groups. As the days of somatostatinmedication increased, the length of the hospital stay rose considerably (P=0.041).Conclusion: We conclude that in acute VB, there is no justification for continuing somatostatin after EVL since it had no beneficialeffect on preventing rebleeding and, instead, increased the risk of ADR and length of hospital stay.

Analysis of risk factors associated with common terminology criteria for adverse event in cancer chemotherapy patients

Background: Chemotherapeutic drugs are commonly associated with various harmful consequences which can remarkably reduce quality life of patient and lengthen hospital admission. The objective of this study was to evaluate the frequency and its associated factors affecting cancer chemotherapy-related side effects in cancer patients. Methods: Patient case report form was used to gather information on the patient's demographics and adverse drug reactions (ADRSs) to chemotherapy medications. ADRs were analyzed for toxicity grade using National Cancer Institute Common Terminology NCI-CTCAE version 4.0. Causality Assessment and Predictability of ADRs were analyzed using World Health Organization' (WHO) Causality assessment scale and Council for International Organization of Medical Sciences (CIOMS) method respectively. Utilizing the chi square test and descriptive statistics, the relationship between the grade of ADRs and the patient's characteristics was investigated. Results: A total of 120 patients were included in the study. Mean age of participant was 46.87 (SD-10.1). Majority (60%) participants were female. 81.7% of total patient received poly-chemotherapy in their treatment modality. Total 412 numbers of ADRs were noted. The most frequent adverse drug reactions were observed to be nausea and vomiting (17.7%), neutropenia and alopecia. On NCI-CTCAE grading maximum number of ADR was assessed as “Grade 2” ADR (33%).

Old age is associated with worse treatment outcome and frequent adverse drug reaction in Mycobacterium avium complex pulmonary disease

BackgroundThe number of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly increasing globally, especially in the older population. However, there is a dearth of evidence regarding the impact of aging on the treatment outcomes of NTM-PD.MethodsWe analyzed consecutive patients who satisfied the diagnostic criteria for Mycobacterium avium complex (MAC)-PD and received antibiotic treatment between January 2009 and December 2020 at a tertiary referral hospital in Korea. The main outcomes were (1) long-term treatment success, defined by negative culture conversion for more than 12 months; and (2) adverse drug reactions (ADRs). Multivariable logistic regression model was used to evaluate the association between age and main outcomes.ResultsA total of 614 patients (median age, 65 years, interquartile range [IQR] 57–73 years; men, 35.3%) were included. Median treatment duration (530 days, IQR 290–678 days; P for trend < 0.001) and long-term treatment success (P for trend = 0.026) decreased, whereas ADRs (P for trend < 0.001) increased significantly with age. Multivariable analyses demonstrated that age ≥ 80 years was an independent factor associated with ADRs (adjusted odds ratio [aOR] 3.29; 95% confidence interval [CI] 1.05–10.28) and worse treatment outcome (aOR 0.42; 95% CI 0.19–0.91).ConclusionsAging is associated with worse treatment outcome and frequent ADRs of patients with MAC-PD. Individualized treatment with reduced-intensity may be a reasonable alternative for older adults.

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study.

The emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p < 0.001). They were younger (median 62 years vs. 70.1 years; p < 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis.

Adverse effects of Anticancer Chemotherapy in Childhood Cancer: A Prospective Study in a Moroccan hospital

Objective: To determine the incidence and frequency of adverse drug reactions (ADRs) induced by cancer chemotherapy in pediatric inpatients. Patients and methods: This was a six-month prospective observational study in the pediatric hematology-oncology department of the children's hospital of Rabat. This study took into account ADRs manifested by in inpatient children and undergoing cancer chemotherapy. A modified version of the Moroccan Poison Control and Pharmacovigilance Centre's notification form was used to collect demographic, clinical, cancer treatment and ADR-related data. The causality, severity and preventability were assessed for each adverse event. Results: 106 patients out of 118 followed have developed a total of 266 ADRs. The most frequent ADRs were anemia (14.3%), infections (9.4%), leukopenia (8.6%) and fever (8.3%). Vincristine (16.3%), etoposide (14%) and cytarabine (13%) were the most frequently administered products. Cytarabine followed by etoposide were the drugs most involved in ADRs. The majority of ADRs (55.6%) were probable according to the WHO method of causality assessment. Conclusion: Cancer chemotherapy is associated with a high risk of developing ADRs, particularly hematological ADRs in children. Pediatric patients receiving cytarabine and daunorubicin combinations and regimens including anthracyclines should receive more attention. Risk management plans need to be implemented by health care teams in this area.

Adverse Drug Reactions of Olanzapine, Clozapine and Loxapine in Children and Youth: A Systematic Pharmacogenetic Review.

Children and youth treated with antipsychotic drugs (APs) are particularly vulnerable to adverse drug reactions (ADRs) and prone to poor treatment response. In particular, interindividual variations in drug exposure can result from differential metabolism of APs by cytochromes, subject to genetic polymorphism. CYP1A2 is pivotal in the metabolism of the APs olanzapine, clozapine, and loxapine, whose safety profile warrants caution. We aimed to shed some light on the pharmacogenetic profiles possibly associated with these drugs’ ADRs and loss of efficacy in children and youth. We conducted a systematic review relying on four databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations and checklist, with a quality assessment. Our research yielded 32 publications. The most frequent ADRs were weight gain and metabolic syndrome (18; 56.3%), followed by lack of therapeutic effect (8; 25%) and neurological ADRs (7; 21.8%). The overall mean quality score was 11.3/24 (±2.7). In 11 studies (34.3%), genotyping focused on the study of cytochromes. Findings regarding possible associations were sometimes conflicting. Nonetheless, cases of major clinical improvement were fostered by genotyping. Yet, CYP1A2 remains poorly investigated. Further studies are required to improve the assessment of the risk–benefit balance of prescription for children and youth treated with olanzapine, clozapine, and/or loxapine.

Adverse effects of gender-affirming hormonal therapy in transgender persons: Assessing reports in the French pharmacovigilance database.

Limited data are available on adverse drug reactions (ADRs) of gender-affirming hormone therapy (HT), mainly due to the lack of population-based studies with adequate controls, thus making spontaneous reporting systems a valuable tool to detect potential side reactions. In this nationwide retrospective study, we aimed to analyze ADRs related to gender-affirming HT reported in the French pharmacovigilance database (FPVD). We requested all the individual case safety reports related to gender-affirming HT recorded in the FPVD before May 27, 2020. We excluded previously published cases and those where gender-affirming HT was not the suspected drug. A total of 28 reports of ADRs were identified. Six concerned transgender men (21-40 years) and 22 transgender women (22-68 years). In transgender men taking testosterone enanthate, all reported ADRs were cardiovascular events, with pulmonary embolism in 50% of cases. Median time to onset (TTO) was 34 months. In transgender women, antiandrogens, mainly cyproterone acetate, were involved in 68% of cases, and estrogens in 77% of cases, mostly in association with progestin or cyproterone acetate. Meningiomas were the principal ADRs, followed by cardiovascular events, with a median TTO of 5.3months. Our data show a previously unreported, non-negligible proportion of cases indicating cardiovascular ADRs in transgender men younger than 40 years. In transgender women, cardiovascular events were the second most frequent ADR. Further research is necessary to identify risk factors that might help to the individualization of treatment strategies. There is a necessity to increase awareness, implement preventive and education measures.

Impact of serotonin transporter (SERT) binding affinity on the risk of libido disorders related to antidepressants

IntroductionSexual dysfunction is a frequent adverse drug reaction (ADR) of antidepressants that considerably affects quality of life and adherence to therapy. We previously investigated the potential underlying neurofunctional mechanisms by neuroimaging methods and revealed a dampening of the dopaminergic mesolimbic-mesocortical reward system along with decreased sexual functioning under serotonergic antidepressants compared to placebo.ObjectivesWithin a combined pharmacoepidemiologic and pharmacodynamic approach, we examined the association between serotonin transporter (SERT) affinity of various antidepressants and corresponding alterations in sexual desire as ADR.MethodsUsing disproportionality analyses, reporting odds ratios (RORs) were calculated for reports indicating decreased sexual desire as ADR under the antidepressants. The data were extracted from the WHO global database of individual case safety reports VigiBase and several MedDRA terms were grouped for “Sexual Desire Disorders”. For the pharmacodynamic assessment, we calculated Pearson correlation coefficients between SERT affinity and corresponding RORsResults16 signals were detected for “Sexual Desire Disorders”. We observed a statistically significant (r (20) =. 65, p = 0.001) association between SERT affinity and decreased sexual desire. Higher SERT affinity was associated with higher risk of sexual desire.ConclusionsWhile sexual dysfunctions under serotonergic medication were previously described, we now elaborated that in particular attenuated sexual desire as ADR is associated with SERT affinity of the antidepressant. These results strengthen our previously described neurofunctional model regarding sexual dysfunction under antidepressant medication and indicate that the specific SERT affinity of the antidepressant drug should be considered in clinical practice to minimize the risk of this ADR.DisclosureNo significant relationships.

Safety and effectiveness of empagliflozin according to body mass index in Japanese patients with type 2 diabetes: a subgroup analysis of a 3-year post-marketing surveillance study

ABSTRACT Background Empagliflozin, a glucose-lowering drug licensed for type 2 diabetes (T2D), demonstrated tolerability and effectiveness overall in a post-marketing surveillance (PMS) study in Japan. However, the impact of body mass index (BMI) is unclear. Research design and methods This was a prespecified sub-analysis of the prospective, 3-year, PMS study of empagliflozin in Japan where the primary endpoint was adverse drug reactions (ADRs). We evaluated results according to BMI. Results We enrolled 7931 T2D patients treated with empagliflozin. Baseline mean age was 58.7 years; 63.01% were male. Baseline BMI was <20 kg/m2 in 2.06% of patients, while 21.28%, 37.35%, and 24.97% had BMI 20–<25, 25–<30 and ≥30 kg/m2, respectively. ADRs occurred in 19 (11.66%), 203 (12.03%), 411 (13.88%), and 295 (14.90%) patients with BMI <20, 20–<25, 25–<30 and ≥30 kg/m2, respectively. Excessive/frequent urination was the most frequent ADR of special interest in all BMI subgroups except 20–<25 kg/m2 (urinary tract infection). Mean change in glycated hemoglobin from baseline was –0.75%, with similar magnitude across BMI subgroups. Body-weight reduction seemed dependent on BMI, with almost no change in the <20 kg/m2 subgroup. Conclusions Empagliflozin appeared well tolerated and effective in Japanese T2D patients regardless of BMI, although the number of patients with BMI <20 kg/m2 was small in this study.

Pediatric Adverse Drug Reactions: An Observational Cohort Study After Health Care Workers' Training.

Adverse drug reactions (ADRs) in children are an important but underestimated public health issue. This study describes ADRs in a registered pediatric population of Bologna and demonstrates that ADRs might be better detected after health care personnel training. A prospective cohort was recruited from July 1, 2016, to June 30, 2019, after health care worker sensitization, and compared to a retrospective cohort enrolled from 2013 to 2016. The ADRs are classified by system organ classes and drugs are categorized according to the Anatomical Therapeutic Chemical classification system. We retrospectively recruited 78 pediatric patients with ADRs in the 2013 to 2016 period, and we prospectively enrolled 127 children in the 2016 to 2019 period. In both periods, most of the ADRs reported were classified as non-serious reactions (68.8%). The most frequent ADRs were general and administration site disorders. During 2013 to 2016 vaccines were the most frequent cause of ADRs (83.3%;) and the main reporters were health care workers other than physicians (84.6%), whereas during the second period, medical doctors become the main signalers (65.4%) and ADRs related to vaccines significantly decreased (55.1%). During the 2016 to 2019 period the number of drug categories was higher than in the 2013 to 2016 period (24 vs 8). Patients with ADRs due to vaccinations present more frequently a favourable outcome (63%). This study demonstrates that active pharmacovigilance and health care personnel sensitization are associated with improved ADR detection, providing valuable information about drugs' safety profile in pediatric patients.

Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis.

Background: The information is relatively scarce regarding the occurrence of drug-induced acute kidney injury (AKI) when anti-coronavirus disease 2019 (COVID-19) drugs are prescribed for patients with diabetes mellitus (DM). Objective: The objective of this study was to evaluate a pharmacovigilance signal for AKI upon the use of common drugs prescribed for COVID-19 treatment, especially in patients with DM. Methods: The FDA Adverse Event Reporting System (FAERS) database were used, and data from the first quarter of 2020 to the third quarter of 2021 were retrieved. A disproportionality analysis was performed to determine whether AKI was more frequently reported with anti-COVID-19 drugs compared to that with other drugs in different populations. Further, reporting odds ratios (RORs) and their 95% confidence intervals (CIs) were used to calculate disproportionality. Results: We identified 33,488 COVID-19 patients and 2397 COVID-19 patients with DM. AKI was the most frequent adverse drug reaction (ADR) reported in this patient population. The primary suspected drugs related to AKI in more than half of the reports (75.60%, 127/168) were four common anti-COVID-19 drugs (remdesivir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir). Compared with other drugs in the same time window, remdesivir and lopinavir/ritonavir were associated with an increased risk of AKI in all COVID-19 patients (ROR: 3.97, 95% CI: 3.51–4.50; ROR: 4.02, 95% CI: 3.11–5.19, respectively). In COVID-19 patients with DM, remdesivir was significantly associated with AKI (ROR: 5.65, 95% CI: 4.06–7.87); meanwhile, there was a new AKI signal associated with tocilizumab (ROR: 2.37, 95% CI: 1.19–4.72). After sensitivity analyses in COVID-19 patients with DM, consistent results for remdesivir were observed; however, the AKI signals for tocilizumab were unstable. Conclusion: Our study confirmed the association of AKI with the usage of common anti-COVID-19 drugs (especially remdesivir and tocilizumab) in DM patients. These safety signals suggested more individualized treatments for COVID-19 patients with comorbidities. Cross-disciplinary collaborative is needed to improve current strategy of clinical treatment and develop new approaches to management.

Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

Abstract P2-13-26: Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer (BC): First real-life data from the cohort temporary authorization for use (cATU) program in France

Abstract Background Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) composed of an HER2-directed antibody and a topoisomerase I inhibitor covalently linked via a tetrapeptide-based cleavable linker. In DESTINY-Breast01, tolerability and efficacy of T-DXd including overall response rate, progression-free survival, duration of response and overall survival have been demonstrated for HER2-positive metastatic and/or unresectable BC in patients (pts) relapsing after 2 or more anti-HER2-based regimens. In France, rapid and fair access to innovative drugs outside clinical trials, prior to their marketing authorization in a given indication, is granted by the French Health Agency, ANSM (Agence Nationale de Sécurité du Médicament et des Produits de Santé), through cATU program. Here we report first real world evidence data from cATU program in HER2+ BC pts treated with T-DXd. Methods T-DXd 5.4mg/kg was given intravenously in monotherapy every 3 weeks in HER2-positive metastatic and/or unresectable BC pts who had previously received at least 2 lines of anti-HER2 regimens in the metastatic setting. Eligible pts needed to have normal neutrophil count and no left ventricular dysfunction. Pts with active or history of interstitial lung disease (ILD), pneumonitis, severe pulmonary disease were excluded. Clinical, biological and safety data were collected until the end of cATU, as well as treatment response according to RECIST 1.1., dose modification, treatment interruption and discontinuation. Analysis was performed on March 31th, 2021 on the basis of available collected data. Results From September 30th, 2020 to March 31th, 2021, 155 centers requested at least one ATU for a total of 539 adult pts; 468 requests were accepted and 71 were refused as they did not meet eligibility criteria. T-DXd was received by 459 pts with the following characteristics: 99.1% were women, median age was 58 years, 90.4% had a ECOG score of 0-1, 98.9% had initial HER2-positive BC (IHC 3+ or IHC 2+/ISH+), 67% were hormone receptor positive. The main sites of metastases were bones (57.3%), lymph nodes (51.6%), lungs (36.2%), liver (33.1%), brain (28.1%) and cutaneous/subcutaneous (13.9%). Median time between initial diagnosis of primary BC and inclusion was 6.6 years (range: 6.6 months - 33.9 years). 81.7% of pts had previously received radiotherapy and 76.5% underwent surgery. The median number of prior cancer regimens in the metastatic setting was 4 (range: 2-22). 21.1% received 2 prior lines of metastatic treatments, 19.6% received 3 lines and 59.3% received 4 lines or more. 94.8% pts received prior trastuzumab emtansine, and 79.3% had prior pertuzumab. During follow-up, data on tumor assessment were available for 160 pts. Of these, 56.7% had complete or partial response and 12.1% had progression. Of the 459 treated pts, 97 pts (21.1%) experienced ≥ 1 Adverse Drug Reaction (ADR) including 41 pts (8.9%) with ≥ 1 serious ADR. Most frequent ADRs were related to gastrointestinal toxicity (35.4%). During cATU, 17 cases (3.7%) with ILD or considered as ILD were reported but no cases had a fatal outcome (only grade 1 or 2 when reported by physicians). 13 fatal cases were reported (no drug-related deaths, attributed by physician). ADRs leading to T-DXd discontinuation were reported in 4 pts (0.9%). Dose reductions were reported in 17 pts (3.7%) and 21 pts (4.6%) had temporary interruptions. Conclusions We report here the first real world data from the French cATU in HER2-positive BC pts treated by T-DXd. The enrolment of 468 pts in 6 months illustrated the unmet medical need for this population. T-DXd had antitumor activity with a similar response rate to that reported in previous clinical studies. T-DXd was well tolerated and no new safety signals were observed. Citation Format: Thierry Petit, Nawale Hajjaji, Eric-Charles Antoine, Marc-Antoine Benderra, Michel Gozy, Cyril Foa, Jean-Loup Mouysset, Julien Grenier, Mireille Mousseau, Audrey Mailliez, Mahasti Saghatchian, Emma Lachaier, Isabelle Desmoulins, Audrey Hennequin, Patricia Maes, Delphine Loirat, Francesco Ricci, Véronique Diéras, Dominique Berton, Florence Lai Tiong, Luis Teixeira, Nadine Dohollou, Christelle Lévy, Thomas Bachelot, Jean-Yves Pierga. Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer (BC): First real-life data from the cohort temporary authorization for use (cATU) program in France [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-26.