Infant adverse reactions to drugs in human milk reported to the Danish Medicines Agency from 2013 to 2023

AimsWe aimed to describe suspected adverse drug reactions (ADRs) in infants resulting from medications transmitted through mothers' milk, as reported to the European ADR database, EudraVigilance. The research sought to understand the frequency, seriousness and nature of these ADRs to assess potential risks associated with maternal medication use during breastfeeding.MethodsData from EudraVigilance were analysed. The study included all reported ADRs suspected to be related to medications transmitted through mothers' milk from 1 January 2013 to 1 July 2023. The data were categorized by reporting time, infant age and sex, seriousness and type of ADR, and the medications involved.ResultsA total of 922 suspected ADRs were reported in breastfed infants. Serious ADRs accounted for 133 cases (14%), with 15 reported fatalities, primarily associated with methadone (n = 11) and diamorphine (n = 3). COVID‐19 vaccines were linked to half of the suspected ADR reports (n = 479, 52%), while serious ADRs were mainly associated with nervous system drugs (n = 73, 43%), particularly anticonvulsants and opioids. Most cases (n = 511, 55%) occurred in infants aged between 1 month and 1 year.ConclusionsThe reporting of 922 ADRs in breastfed infants over a decade, compared to the estimated millions of infants exposed to medications via mothers' milk annually in Europe, suggests a very low reporting rate of suspected ADRs. This finding emphasizes the significant challenges in postmarketing surveillance and suggests that underreporting remains a critical concern in pharmacovigilance.

The types and rate of adverse drug reactions experienced by breastfed infants whose mothers are taking medications has not been well defined. This article reviews the literature on adverse drug reactions in infants since a previous review in 2002. Case reports and studies of adverse drug reactions in breastfed infants whose mothers were taking a prescribed or over-the-counter medication were selected. Fifty-three case reports and 16 studies were located. Serious acute adverse drug reactions from drugs in breastmilk appear to be uncommon. Infants under 2 months of age, and especially those under 1 month, appear to be most susceptible. Similar to previous reviews, free iodine, opioids, and the use of multiple central nervous system drugs simultaneously were identified as drugs of concern. A few narrowly focused studies are now available on long-term effects of maternal drug therapy on breastfed infants and they are mostly reassuring.

Drug therapy is a powerful tool to improve outcome, but there is an urgent need to improve pharmacotherapy in neonates through tailored prevention and management of adverse drug reactions (ADRs). At present, infants commonly receive off-label drugs, at dosages extrapolated from those in children or adults. Besides the lack of labelling, inappropriate formulations, (poly)pharmacy, immature organ function and multiple illnesses further raise the risk for ADRs in neonates and infants. Pharmacovigilance to improve the prevention and management of ADRs needs to be tailored to neonates and infants. We illustrate this using prevention strategies for drug prescription and administration errors (e.g. formulation, bedside manipulation, access), detection through laboratory signalling or clinical outlier data (e.g. reference laboratory values, overall high morbidity), assessment through algorithm scoring (e.g. Naranjo or population specific), as well as understanding of the developmental toxicology (e.g. covariates, developmental pharmacology) to avoid re-occurrence and for development of guidelines. Such tailored strategies need collaborative initiatives to combine the knowledge and expertise of different disciplines, but hold promise to become a very effective tool to improve pharmacotherapy and reduce ADRs in infants.

Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all 2359 children were examined. ADR were recorded in 63 children and were reported to the National ADR monitoring centre in Zagreb. Using the algorithm of Hutchinson et al. (1979), all ADR were classified as "definite", "probable", "possible" and "unlikely". Drugs were prescribed in 97.3% of children, 60.24% received an antimicrobial agent (43% of them on the basis of a sensitivity test), and an antipyretic was given to 1878 children, mostly paracetamol. ADR were most frequently caused by antibiotics (49 reactions to penicillin V, and 15 to amoxycillin) and secretolytics (7 reactions). ADR were followed by complete recovery and not a single child was hospitalized because of an ADR. The results, when compared with the very small number of broadly comparable studies, indicate that the incidence of ADR in this population is rather small and of minor importance.

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia’s national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia’s National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens–Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children.

BackgroundSeveral reports have been published about the impact of coronavirus disease 2019 (COVID-19) vaccines on human health, and each vaccine has a different safety and efficacy profile. The aim of this study was to reveal the nature and classification of reported adverse drug reactions (ADRs) of the two COVID-19 vaccines (tozinameran and ChAdOx1) among citizens and residents living in Saudi Arabia, and show possible differences between the two vaccines and the differences between each batch on the health of populations.MethodsA cross-sectional study was conducted in Saudi Arabia between December 2020 and March 2021. Saudi citizens and residents aged ≥ 16 years who had at least one dose of any batch of either of the two approved COVID-19 vaccines (tozinameran and ChAdOx1) and who reported at least one ADR from the vaccines were included. The study excluded people who reported ADRs after receiving tozinameran or ChAdOx1 vaccines but no information was provided about the vaccine’s batch number.ResultsDuring the study period, 12,868 vaccinated people, including a high-risk group (i.e., those with chronic illness or pregnant women), reported COVID-19 vaccine ADRs that had been documented in the General Directorate of Medical Consultations, Saudi Ministry of Health. The study reported several ADRs associated with COVID-19 vaccines, with the most common (> 25%) being fever/chills, general pain/weakness, headache, and injection site reactions. Among healthy and high-risk people, the median onset of all reported ADRs for tozinameran and ChAdOx1 vaccine batches were 1.96 and 1.64 days, respectively (p < 0.01). Furthermore, significant differences (p < 0.05) were recorded between the two studied vaccines in regard to fever/chills, gastrointestinal symptoms, headache, general pain/weakness, and neurological symptoms, with higher incidence rates of these ADRs observed with the ChAdOx1 vaccine than the tozinameran vaccine. However, the tozinameran vaccine was found to cause significantly (p < 0.05) more palpitation, blood pressure variations, upper respiratory tract symptoms, lymph node swelling, and other unspecified ADRs than the ChAdOx1 vaccine. Among patients vaccinated with seven different batches of the tozinameran vaccine, people vaccinated with the T4 and T5 batches reported the most ADRs.ConclusionThere were significant differences regarding most of the reported ADRs and their onset among tozinameran and ChAdOx1 vaccines on both healthy people and high-risk individuals living in Saudi Arabia. Moreover, the study found that the frequencies of most listed ADRs were statistically different when seven batches of tozinameran vaccine were compared.

BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of adalimumab in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering...

BackgroundResearch regarding adverse drug reactions (ADRs) associated with the use of etanercept in patients with inflammatory rheumatic diseases (IRDs) usually focuses on the nature and frequency of ADRs without considering...

Disproportionality analysis of anaphylactic reactions after vaccination with messenger RNA coronavirus disease 2019 vaccines in the United States

Despite their frequent use in children and adolescents, the evidence for efficacy and safety of antidepressants (ATDs) in this population is scarce and off-label prescribing common. The aim of this study was to describe reported adverse drug reactions (ADRs) associated to ATDs over a 30-year period using the French Pharmacovigilance Database (FPVD). We performed an analysis of ADRs registered in the FPVD from 1985 to 2016, occurred in children and adolescents receiving an ATD. Descriptive statistics were used to obtain an overview of ADRs types and characteristics, and data were stratified by age. Among the 45,070 pediatric cases reports registered into the FPVD, we identified 1366 reports (3.0%) in which ATDs were "suspected" as the cause of 2922 ADRs. ADRs were more frequently reported in female (n = 743; 55.5%) and adolescents (n = 627; 49.3%). Neuropsychiatric ADRs were the most reported, mainly sleepiness, agitation, and suicidal thinking and behavior, followed by gastrointestinal and hepatobiliary disorders, mainly vomiting, abdominal pain, hepatitis, nausea, and three unexpected ADRs of pancreatitis. There was an increase of annual reporting between 1986 and 2003, followed by a plateau state then a decrease from 2003 to 2012, and a rapid escalation until 2016, while an increase in the number of reporting of suicidal thinking and behavior was observed after 2003, highlighting a possible impact of black box warnings on reporting practices and ATD use. This pediatric pharmacovigilance study underscored the high prevalence of neuropsychiatric and gastrointestinal ADRs, including three unexpected cases of pancreatitis.

Safety of COVID-19 vaccination in patients with clonal mast cell disorders

Introduction Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. Methods We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. Results 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. Conclusion This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

Background: COVID-19 vaccines have been developed rapidly to combat the pandemic, but vaccine hesitancy remains a challenge due to concerns about adverse drug reactions (ADRs). This study aimed to compare the ADR profiles of COVID-19 vaccines with established vaccines and investigate differences between adults and children.&#x0D; Methods: A retrospective observational study used the VAERS database to analyze ADR reports from January 2021 to December 2022 in the United States. Top ten common ADRs and seven severe ADRs associated with COVID-19 vaccines were studied using the Evans Criteria.&#x0D; Results: Among the common ADRs, only dyspnea showed disproportionate reporting in COVID-19 vaccines. Severe ADRs, including myocarditis, pneumonia, and cerebrovascular accidents, were disproportionately reported. Age-stratified analysis revealed myocarditis disproportionately reported in both adults and children.&#x0D; Conclusions: This study provides a comprehensive comparison of ADRs between COVID-19 vaccines and established vaccines. Although some severe ADRs were disproportionately reported, further evaluation is required to establish any causal relationships with COVID-19 vaccine. Continuous monitoring of ADRs is crucial for vaccine safety.

Consumer reporting of adverse drug reactions: Systems that allow patients to report side effects of the drugs they are taking have yielded valuable information for improving drugs safety and health care.