Anti-infectives For Systemic Use Research Articles

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Analysis of the Russian Database of Spontaneous Reports

(1) Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design—a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%—TEN. In total, 30% were pediatric SRs, 21.2%—SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.

Drug-induced Tongue Disorders: A Comprehensive Literature Review.

Some drugs cause tongue disorders as adverse effects. Most of the druginduced tongue disorders are benign and will resolve after drug discontinuation. However, the changes in the color or appearance of the tongue may frighten patients and decrease compliance with drug therapy. To review the literature to find all reports of drug-induced tongue disorders, their presentation, management, and outcome of patients Methods: The search was conducted in Google Scholar and PubMed using key words "ageusia," "burning tongue," "coated tongue," "drug-induced taste disturbances," "dysgeusia," "glossitis," "glossodynia," "hairy tongue," "hypogeusia," "stomatodynia," "stomatopyrosis," "swollen tongue" "tongue discoloration," "tongue irritation," "tongue numbness, "tongue oedema," and "tongue ulcer. All reports that were published from 1980 to 2022 in the English language were included in the study. Reports that were not in English language but had English abstracts with adequate data for extraction were also included. A total of 208 case reports and case series were included. The most reported drug classes were antineoplastic and immunomodulating agents and anti-infectives for systemic use, and the most common tongue disorders were tongue discoloration and black hairy tongue. Having good oral hygiene and discontinuing the offending drug could manage and resolve the problem. Drug-induced tongue disorders are not rare adverse drug reactions. They are benign in most cases, and withholding offending agents results in significant improvement or complete resolution of tongue lesions.

Risk of drug-induced delirium in older patients- a pharmacovigilance study of FDA adverse event reporting system database

ABSTRACT Background Drug-induced delirium is one of the numerous known risk factors associated with increased morbidity and mortality in older patients. The objective of this study was to evaluate the risk of drug-related delirium in older patients based on the FDA Adverse Event Reporting System (FAERS). Research design and methods Delirium reports in older patients (age ≥65) from 2004 quarter 1 through 2021 quarter 3 extracted from the FAERS database using Open Vigil 2.1. The reported odds ratio and the proportional r7eported ratio were calculated to detect the adverse reaction signal of delirium. Combined with published evidence, suspected drugs were categorized as known, possible, or new potential delirium-risk-increasing drugs. Results Of the 130,885 reports (including 28,850 delirium events and 1,857 drug) analyzed for this study, 314 positive signal drugs were detected. Positive signal drugs are mainly concentrated on the drug of nervous system [n = 149, ROR 3.60, 95% CI (3.56–3.64)], cardiovascular system [n = 35, ROR 1.45, 95% CI (1.43–1.47)], alimentary tract and metabolism [n = 35, ROR 1.25, 95% CI (1.23–1.26)] and anti-infectives for systemic use [n = 27, ROR 1.70, 95% CI (1.66–1.74)]. Of the positive signal drugs, 26.11% (82/314) were known delirium-risk increasing drugs [ROR 4.12, 95%CI (3.85–4.41)], 44.90% (141/314) were possible [ROR 3.59, 95%CI (3.37–3.83)] and 28.98% (91/314) were new potential [ROR 3.68, 95%CI (3.22–4.21)]. Conclusion Drug-induced delirium risk is prevalent in the older patients according to the FAERS. The risk level of drug-induced delirium should be taken into account to optimize drug therapy in clinical practice.

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.

Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.

To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

Evaluation of adverse drug reactions to off-label use of drugs in children from spontaneously reported cases at a tertiary care hospital

Background: Off-label use of drugs (OLUDs) is relatively common in pediatric and this may be associated with adverse drug reactions (ADRs). The studies about the safety of drugs used in children cannot be applied to safety of drugs during OLUDs as drug is used in way that is different from that described in regulatory body. Hence, it is worthwhile to evaluate the off-label status of the suspected drugs causing ADRs. Aims and Objectives: The aim of the study was to analyze the pattern of ADRs occurring during OLUDs in pediatric patients from the spontaneously reported ADRs cases at the pharmacovigilance unit of a tertiary care hospital. Materials and Methods: Single center, retrospective, observational study was conducted in the department of pharmacology. ADRs spontaneously reported from January 2016 to December 2017, which occurred during OLUDs in children, where causality is certain, probable and possible. Results: A total of 46 ADRs occurred during OLUDs in 44 patients, these patients received 174 medicines among which 66 were off-labeled drugs. Off-label drugs mainly belonged to anti-infectives for systemic use (70.31%) and it is associated with 30 ADRs (68.18%). The most commonly affected organ system is skin and subcutaneous tissue (43.18%). Conclusion: OLUDs is associated with ADR, so caution should be taken while prescribing a drug in off-label manner in children.

Two Years of Active Pharmacovigilance Surveillance and Therapeutic Reconciliation in Frail Populations: The MEAP 3.0 Study

Awareness related to the risk/benefit profile of therapies used in paediatric and elderly patients is limited. We carried out a study, called the MEAP 3.0 study, to collect and analyse evidence of adverse drug reactions (ADRs) and drug–drug interactions (DDIs) that occurred in frail populations under polypharmacy in a real-world setting. Data were retrieved from reports of ADRs and pharmacological counselling from patients treated in hospitals and territorial health services. We collected 2977 ADRs reports and identified ‘anti-infectives for systemic use’ and ‘cardiovascular system’ as the most frequently implicated pharmacological classes in under-18 and over-65 patients, respectively. We detected 2179 DDIs, of which 10.7% were related to at least one ADR: 22 were classified as ‘contraindicated’ (7 in the paediatric group and 15 in the elderly one), and 61 as ‘major’ (6 in the paediatric patients and 55 in the geriatric ones), while 151 DDIs were classified as ‘moderate’ (10 referred to paediatric population, and 109 to elderly patient) and as ‘minor’ (1 in paediatric patients, and 31 in the elderly ones). The MEAP 3.0 project demonstrates that pharmacovigilance surveillance and therapeutic reconciliation are valid strategies to avoid potential DDIs and the occurrence of ADRs, allowing for personalised medicine.

Off-label and unlicensed drug use in a Spanish Neonatal Intensive Care Unit

ObjetiveTo describe off-label and unlicensed drugs in clinical practice in a Neonatal Intensive Care Unit (NICU). MethodThe design of the study was a descriptive and retrospective three months research in a NICU of a Spanish University Hospital. All prescriptions were classified as approved, off-label and unlicensed drug used, according to the information available on the Summary of Product Characteristics. Off-label drugs prescriptions were divided into four groups (dose, frecuency, age and indication of use) depending on the reason of disconformity. ResultsForty-one neonates were included (46.3% premature patients) and a total of 273 drug prescriptions were evaluated. Of them, 53.1% (145) were classified as an approved drug prescriptions, 41.4% (113) were off-label use and 5.5% (15) were unlicensed drugs. 90.2% of the patients (37/41) received at least one off label prescription, with a median of 3 (range 1-7). Age was the foremost reason for off-label use (42.5%), followed by dose (31.0%), frecuency (16.8%) and dose-frecuency off-label drug use (8.8%). The last place was reserved for off-label drug use by indication (0.9%). Group J (corresponding with antiinfectives for systemic use) was the most frecuently prescribed, with ampicillin (18.6%) and gentamicin (16.8%) as the drugs most commonly use as off-label prescriptions. Finally, caffeine citrate was the unlicensed drug most frecuently prescribed. ConclusionsOff-label and unlicensed drug use prescriptions in our NICU clinical practice are highly frecuent as other authors have previously published in other countries where they were studied. Although there are few studies in newborn patients, both off-label and unlicensed drug prescriptions are commonly recomended in Paediatrics Guidelines.

Multicentric study on the incidence and preventability of medication-related incidents in patients visiting pediatric emergency departments

ObjectiveTo determine the incidence, severity, and preventability of medication-related incidents in patients visiting pediatric emergency departments, and to identify the highest-risk age groups and the drugs most frequently involved. MethodThis is a multicenter prospective observational study carried out between March and June 2017 in patients between 0 and 16 years of age who visited the pediatric emergency department of eight Spanish public hospitals. We recorded and assessed three different types of incidents: adverse drug events, medication errors, and accidental self-poisoning. Incidents were characterized according to severity, preventability, age groups affected, and drugs involved. ResultsDuring the study period, a total of 99,797 visits were recorded to the pediatric emergency departments following 334 drug-related incidents in as many patients, of whom 52.4% were male, with a mean age of 47.1 ± 44.4 months. The incidence of patients with drug-related incidents was 0.3%. Of the total incidents, 264 (79%) were considered preventable and 158 (47.3%) had caused harm to patients. Incidents detected included 144 (43.1%) adverse drug events, 218 (65.2%) medication errors (74 of them leading to harm; these are also included as preventable drug-related adverse events), and 46 (13.7%) cases of accidental self-poisoning. Preschoolers (1-5 years of age) represented 60.8% of incidents and were the age group with the highest percentage of preventable incidents (64%). A total of 351 drugs were involved in the 334 incidents detected, most of which fell into one of three therapeutic groups: anti-infectives for systemic use (171; 48.7%), nervous system (66; 18.8%) and respiratory system (41; 11.7%). ConclusionsThe incidence of drug-related incidents in pediatric patients presenting to emergency departments was lower than that reported for adult patients, although almost half of the incidents identified were associated with harm. Preschool patients (1-5 years of age) were identified as the age group at the highest risk. The recorded incidents were caused by a small number of drugs. A high percentage of incidents were preventable, which confirms the urgent need to implement medication incident prevention strategies for this population.

Neonatal ICU therapy: a literature review on pharmacotherapies

INTRODUCTION: The neonatal period is an age group of vulnerability, which is subject to adverse effects related to conventional drug treatments and therapies, many drugs are empirically applied in the neonatal ICU (NICU), in off-label or non-licensed ways, currently the scientific basis on pediatric pharmacological assistance is scarce, constituting an unpredictable scenario of adverse and severe drug reactions. OBJECTIVE: To analyze the main pharmacological practices in the neonatal ICU, observing the possible effects on the newborn patient. METHODOLOGY: literature review that used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The search for articles was carried out in PubMed, SciELO and LILACS databases, applying descriptors from Descritores em Ciências da Saúde (DeCS) and Medical Subject Headings (MeSH). RESULTS: 415 articles were found and 26 were included in the study. It was noted that there is a high prevalence of overdoses and unnecessary prolongation of antibiotic therapy, adverse effects linked to bacterial resistance and alteration of the newborn’s (NB) microbiota may occur, generally these drugs were used in the scenario of neonatal sepsis and in an off-label way, vancomycin stood out as the most widely used antibiotic among the studies. The NB’s respiratory problems were pharmacologically treated with exogenous surfactant, propofol, hydrocortisone and milrinone, the clinical situations of use include Respiratory Distress Syndrome in Neonates and sedation for intubation. Painful procedures are common in the NICU, requiring pharmacological measures such as the use of analgesics and sedatives, including fentanyl, morphine, dipyrone, non-steroidal anti-inflammatory drugs and benzodiazepines, the safe application is also difficulty with these medications. Local anesthetics, such as lidocaine, are the most used for surgical pain, epidural anesthesia helps to reduce surgical stress, and topical anesthetics are useful for pain caused by skin barrier rupture. The group of drugs most used in an off-label way, according to the Anatomic Therapeutic Chemical (ATC) classification, were the group of anti-infectives for systemic use and drugs that act on the nervous system. CONCLUSION: the need for more scientific depth in the context of pharmacology at the NICU became extremely explicit during the study’s development, the lack of consensus for appropriate medical prescriptions leads to the need for greater care when prescribing for neonates, considering the inherent characteristics of the organism of these patients that alter the pharmacokinetics and pharmacodynamics of medications.

Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial.

Diabetes negatively impacts cancer prognosis. The objective of this work was to evaluate a tripartite oncologist-pharmacist-diabetologist collaboration in the management of patients with diabetes starting chemotherapy. The prospective ONCODIAB study (NCT04315857) included 102 adults with diabetes starting chemotherapy by whom a continuous glucose monitoring device was worn for fourteen days from the first day of the first and second chemotherapy cycles. The primary outcome was to assess pharmacist and diabetologist interventions. The secondary outcome was to evaluate the impact of the ONCODIAB follow-up on individualized patient glycemic targets at 6 months. A total of 191 (2 per patient) were made either by clinical pharmacists (n = 95) or diabetologists (n = 96) during the first two chemotherapy cycles. The anatomic therapeutic chemical drug classes most frequently involved in pharmacist interventions were cardiovascular system (23%), alimentary tract and metabolism (22%), and anti-infectives for systemic use (14%). Diabetologists modified the antidiabetic treatment in 58 (62%) of patients: dose reduction (34%), drug discontinuation (28%), drug addition (24%), and dose increase (15%). Glycated hemoglobin decreased from 7.6 ± 1.7% at baseline to 7.1 ± 1.1% at 6 months (p = 0.02). Compared to individualized targets, HbA1c was higher, in the interval, or lower in 29%, 44%, and 27% of patients at baseline vs. in 8%, 70%, and 22% of patients at 6 months, respectively (p < 10-3). In our study, a close collaboration between oncologists, pharmacists, and diabetologists helped by continuous glucose monitoring led to overall medication optimization and better glycemic control in patients with diabetes starting chemotherapy.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil

BackgroundThe increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil.MethodsCross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy.ResultsA total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy.ConclusionsWe found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.

Reports of Symptoms Associated with Supraventricular Arrhythmias as a Serious Adverse Drug Reaction in the Spanish Pharmacovigilance Database.

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

Patterns of adverse drug reactions in Jordan: a retrospective analysis of the National Pharmacovigilance Data Registry (2015–2021)

ABSTRACT Background Post-marketing surveillance of drugs is a cornerstone of pharmacovigilance. This study was conducted to characterize patterns of adverse drug reactions (ADRs) reported in Jordan. Research design and methods ADR reports submitted to the pharmacovigilance database of the Jordan Food and Drug Administration during 2015–2021 were retrospectively analyzed. The most commonly reported drugs, drug classes, ADRs, and ADRs consequences were explored. Logistic regression identified possible predictors of reporting serious ADRs. Results A total of 2744 ADR reports were included, among which 28.4% were classified as serious. An annual increase in ADR reporting was observed. The most commonly implicated drug classes were antineoplastic and immunomodulating agents (24.0%), anti-infectives for systemic use (14.2%), and alimentary tract and metabolism (12.1%). Covid−19 vaccination was the most reported drug (22.8%). Fatigue (6.3%), injection site pain (6.1%), and headache (6.0%) were the top three common ADRs. Among ADRs with outcome information, 4.7% were fatal. Patient’s age and intravenous medication use largely predicted reporting serious ADRs. Conclusions This study provides contemporary insights into the post-marketing surveillance of drugs in Jordan. The findings are foundational for future studies exploring drug-ADRs causality relationships. Efforts that promote pharmacovigilance concepts should be sustained and enhanced at the national level.

Prescribed Drugs and Self-Directed Violence: A Descriptive Study in the Spanish Pharmacovigilance Database.

Self-inflicted violence is a major and growing public health problem and its prediction and prevention is challenging for healthcare systems worldwide. Our aim was to identify prescribed drugs associated with self-directed violent behaviors in Spain. A descriptive, longitudinal and retrospective study of spontaneous reports of adverse drug reactions corresponding to self-directed violence was recorded in the Spanish Pharmacovigilance Database (FEDRA®) from 1984 to 31 March 2021. A total of 710 cases were reported in the study period. The mean age was 45.52 years (range 1-94). There were no gender differences except in children, where most reports were of male children. The main therapeutic groups that were involved included drugs for the nervous system (64.5%) and anti-infectives for systemic use (13.2%). The most commonly reported drugs were varenicline, fluoxetine, lorazepam, escitalopram, venlafaxine, veralipride, pregabalin, roflumilast and bupropion. There were reports of montelukast, hydroxychloroquine, isotretinoin, methylphenidate, infliximab, natalizumab, ribavirin and efavirenz, which were less known to be involved in self-directed violence. This study shows that self-directed violence is a rare adverse drug reaction, and can be related to the use of some medicines. It is important for healthcare professionals to consider this risk in their clinical praxis, implementing person-centred approaches. Further studies are needed, considering comorbidities and potential interactions.

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.

Drug-induced tooth discoloration: An analysis of the US food and drug administration adverse event reporting system.

Background: Certain drugs can cause intrinsic or extrinsic tooth discoloration, which is not only a clinical issue but also an esthetic problem. However, limited investigations have focused on drug-induced tooth discoloration. The present work aimed to determine the drugs causing tooth discoloration and to estimate their risks of causing tooth discoloration. Methods: An observational, retrospective, and pharmacovigilance analysis was conducted, in which we extracted adverse event (AE) reports involving tooth discoloration by using the data of the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021. Disproportionality analyses were performed to examine risk signals for tooth discoloration and determine the drugs inducing tooth discoloration. Results: Based on predefined inclusion criteria, 1188 AE reports involving 302 suspected drugs were identified. After data mining, 25 drugs generated positive risk signals for tooth discoloration, of which 10 were anti-infectives for systemic use. The top reported drug was tetracycline (n = 106), followed by salmeterol and fluticasone (n = 68), amoxicillin (n = 60), chlorhexidine (n = 54), and nicotine (n = 52). Cetylpyridinium (PRR = 472.2, ROR = 502.5), tetracycline (PRR = 220.4, ROR = 277), stannous fluoride (PRR = 254.3, ROR = 262.8), hydrogen peroxide (PRR = 240.0, ROR = 247.6), and chlorhexidine (PRR = 107.0, ROR = 108.4) showed stronger associations with tooth discoloration than the remaining drugs. Of 625 AE reports involving 25 drugs with positive risk signals, tooth discoloration was mostly reported in patients aged 45-64 (n = 110) and ≤18 (n = 95), and 29.4% (192/652) of the reports recorded serious outcomes. Conclusion: This study revealed that certain drugs are significantly associated with tooth discoloration. Caution should be exercised when using these drugs, especially during pregnancy and early childhood.

Profile of Drug Utilization in Patients with Rare Diseases in Tuscany, Italy: A Population-Based Study

Patients with rare diseases (RDs) generally have delayed diagnosis and misdiagnosis, which lead to inappropriate care or the need to modify treatment during the course of the disease. The medical care of RD patients can be further complicated by the presence of comorbidities. In this population-based study, we evaluated the prevalence, intensity of use, and consumption of drugs prescribed to RD patients residing in Tuscany (Italy) in the years 2008-2018. Data from the Registry of Rare Diseases of Tuscany were integrated with information retrieved from regional pharmaceutical prescription databases. The overall prevalence of drug use in the RD patients was 85.4%. Drugs for the alimentary tract and metabolism and antiinfectives for systemic use showed the highest prevalence of use, while drugs for the nervous system had the highest intensity of use only in the pediatric patients. The adults exhibited a female preponderance in terms of the prevalence of use and drug consumption in almost all the age groups and therapeutic categories. Conversely, a higher prevalence of use was observed in the male children. These results provide relevant insights into drug profiles in RD patients, representing a first step for future analyses to monitor changes in drug utilization in patients with RDs over time.

Trends in National Pharmaceutical Expenditure in Korea during 2011 - 2020.

This study aimed to identify the trends in pharmaceutical expenditure (PE), share of PE in health expenditure (HE), and trends in expenditure by pharmacological groups (ATC level 1 classification) in Korea for a 10-year period (2011 - 2020) and compare the data with those of other Organisation for Economic Co-operation and Development (OECD) countries. Using the findings, we determined the current status of pharmaceutical expenditure (PE) management in Korea and derived the implications for establishing future macroscopic policies on PE. We analyzed the OECD Health Statistics and the Korean national health insurance claims database from January 2011 through December 2020. The outcome measures were HE, PE, and pharmaceutical sales data for ATC level 1 medicines from OECD Health Statistics data during 2011 - 2020. As OECD collects limited ATC level 1 data, we used the HIRA health insurance claims data for PEs of ATC level-1 classification, including D, L, P, and S. PE in Korea increased by 38.5% from 19.9 billion USD in 2011 to 27.6 billion USD in 2020, whereas the share of PE in HE decreased by 6.3%p from 26.4% in 2011 to 20.1% in 2020. In 2020, Korea ranked third in PE per capita (760.9 USD PPP) and had the highest share of PE (20.1%) among the 19 OECD countries studied. By ATC level 1 class, the highest PE was A (alimentary tract and metabolism) at 4.3 billion USD, and L (antineoplastic and immunomodulating agents) had the highest increase at 13.4%; in contrast, J (anti-infectives for systemic use) had the lowest increase in annual average PE at -0.2% in 2020 relative to 2011. Among the 17 OECD countries, Korea had the highest and the third-highest expenditures for ATC codes A and J, respectively. PE in Korea has continued to increase between 2011 and 2020, indicating the need for macroscopic management of PE. Our results on PE by ATC code may help health authorities in establishing future policies on PE.

Trends in Adverse Drug Reactions Among Children: Evidence from Jiangsu Province of China, 2010-2019.

Medication safety among children represents an underrecognized public health concern worldwide, yet little evidence was found in China. This study aimed to examine trends in rates of pediatric adverse drug reaction (ADR) reports in Jiangsu Province of China with a catchment population of more than 11 million children. Data for children aged under 15 years were extracted from the spontaneous reporting system of ADR surveillance in Jiangsu Province. Suspected therapeutic agents for ADRs were coded using the Anatomical Therapeutic Chemical classification system. We used the Chinese modification of the International Classification of Diseases, Tenth Revision, to group primary diseases, and the Medical Dictionary for Regulatory Activities to classify the manifestation of ADRs. We used Joinpoint to estimate age-adjusted ADR rates stratified by sex from July 2010 to June 2019, and further by specific features, including patient characteristics, main suspected therapeutic medications, primary diseases, and ADRs. We used the percentage change annualized estimator to evaluate trends over time. A total of 79,903 ADR reports were identified among children aged under 15 years, which accounted for 11.4% of all ADRs reported in Jiangsu Province during the same period. The age-adjusted ADR report rates increased significantly from 66.20 to 96.76 per 100,000 children during the period July 2010-June 2019, with an annual increase of 4.9% (95% confidence interval 1.3-8.5%; p value 0.014). Of all ADR reports, there were 47,774 (59.8%) boys and 32,129 (40.2%) girls. Children aged 0-4 years accounted for more than half of the ADR reports (n=47,680, 59.7%). Skin and subcutaneous tissue disorders were the most frequently reported ADRs (45,773, 57.3%). Respiratory diseases were the most commonly observed medical conditions in relation to pediatric ADRs, accounting for 68.8% (n=54,940) of all ADR reports, and anti-infectives for systemic use consistently represented over time the most common medication group, contributing to 69.8% of all reports. A reduction in ADR report rates was observed for vaccines, with an annual decrease of 19% in children. ADRs remain a public health challenge among the vulnerable pediatric populations. Findings from the present study call for continuing efforts in ADR prevention and medication safety improvement in children.