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Antipsychotic prescribing trends vary internationally, albeit off-label use remains high (i.e., target symptoms). We aim to describe antipsychotic use, target conditions, target symptoms and dosing regimens in children and adolescents in Ireland. We used a sampled cohort from a national audit of children and adolescents attending mental health services with predefined inclusion and exclusion criteria from Jul-2021 to Dec-2021 who were prescribed at least one psychotropic medication and up to and including 17-years of age (n = 3528). Each service provided anonymised data. We described the frequency of antipsychotic medication, medication type, target condition, target symptom and medication doses. We used multivariable logistic regression, adjusted with available co-variates to assess the association of being prescribed an antipsychotic medication. Twelve percentage (n = 437) were prescribed an antipsychotic and 16–17-years (n = 211, 48.3%) was the most common age category. The commonest reason for prescribing an antipsychotic was target symptoms (i.e., off-label use) (n = 329; 75.%) and of these symptoms, agitation (n = 77/329; 25%) and irritability (56/239; 25%) were the most common. Quetiapine (n = 127; 29%) was the most common antipsychotic, followed by risperidone (n = 125; 28.6%), aripiprazole (n = 107; 24.5%), and olanzapine (n = 66; 15.1%). In adjusted analysis, having a psychotic disorder ((adjusted-odds-ratio) aOR: 39.63, CI 95%, 13.40–117.22), bipolar disorder (aOR: 16.96, CI 95%, 3.60–80.00), autism spectrum disorder (aOR: 3.24, CI 95%, 2.45–4.28) or aggression symptoms (aOR: 16.75, CI 95%, 7.22–38.89) was associated with prescribing an antipsychotic medication. This is the first study in children and adolescents that describes the target conditions and target symptoms for antipsychotic use in Ireland. Our results show a high proportion of antipsychotic prescribing based on target symptoms rather than target condition or diagnosis. [ABSTRACT FROM AUTHOR]

Ketamine is a versatile anesthetic that has been widely used off-label to treat a variety of indications. Esketamine, a derivative of ketamine, is FDA-approved to treat treatment-resistant depression. This report compares statewide prescription ketamine and esketamine trends. Using PDMP data from 2017–2023, prescription and prescriber characteristics, and patient demographics were compared between esketamine and ketamine prescriptions. During this time, ketamine prescriptions, patients, and providers rose 55.8%, 30.6%, and 2.8% since 2017. Esketamine prescriptions increased 1289.4% since 2019. In 2023, ketamine prescriptions were primarily in powder form (98.7%) and paid for out-of-pocket (83.9%), whereas esketamine prescriptions were primarily paid for by insurance (80.2%). The proportion of ketamine prescribed in RI but dispensed out-of-state have increased 22% since 2022 (18% of total dispensations). As more people seek treatment for mental health disorders, ketamine and esketamine prescriptions continue to rise. Understanding ketamine and esketamine use can help mitigate associated adverse events. [ABSTRACT FROM AUTHOR]

Abrocitinib, an oral small-molecule Janus Kinase 1 (JAK1) inhibitor, is primarily approved for treating moderate-to-severe atopic dermatitis (AD) in adults and adolescents aged 12 and older. This review examines the emerging off-label uses of Abrocitinib. We identified 37 papers reporting on the use of Abrocitinib in various conditions other than AD. The most commonly reported uses were for vitiligo, prurigo nodularis, and hand eczema, with 12 cases each. There were also 10 cases of lichen sclerosus and chronic pruritus of unknown origin and 5 cases each of pityriasis rubra pilaris alopecia areata. Additionally, erythematotelangiectatic rosacea and steroid-induced rosacea were reported in four cases each. Other conditions treated with Abrocitinib were noted, but these mostly had only one or two reported cases. Interestingly, out of the 103 patients reviewed, all studies reported favorable clinical outcomes and satisfactory results, with the exception of one isolated case where Abrocitinib was used to treat erythematotelangiectatic rosacea. [ABSTRACT FROM AUTHOR]

Background: Continuous pulse oximetry (Sp o 2) is a commonly utilized tool to obtain an indirect, noninvasive measurement of hemoglobin oxygen saturation. Difficulty obtaining measurement with Sp o 2 sensors can lead nurses to try off-label sites until they find placement that provides a signal. Currently, there is limited evidence to support this application. Purpose: The purpose of this study was to evaluate the accuracy of off-label placement of pulse oximetry sensors in comparison to on-label placement in adult cardiac intensive care patients. Methods: Data were collected on 24 participants. At the time of a medically necessary arterial blood gas laboratory draws, 4 Sp o 2 measurements were gathered from an on-label finger sensor, an off-label finger sensor, an on-label ear sensor, and an off-label ear sensor. Results were analyzed using 4 Pearson correlation coefficients, Bland-Altman plots, and 2 linear mixed-effect models. Results: Our study found that while both our on-label finger and off-label finger pulse oximetry sensor overestimated when compared to the arterial hemoglobin saturation (gold standard), there was greater overestimation found with the off-label placement. Though there was not a significant difference observed between the ear probe on the nose and the gold standard, figures examining off-label ear probe and gold standard measures show that, in lower ranges of oxygen saturation, the off-site probe substantially overestimates true oxygen saturation, while in higher ranges of oxygen saturation, the off-site ear probe underestimates true oxygen saturation. Conclusions: No changes should be made to the current practice of using pulse oximetry sensor placement. [ABSTRACT FROM AUTHOR]

Background: Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions. Methods: In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis. Results: Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment. Conclusion: In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments. [ABSTRACT FROM AUTHOR]

AbstractThe management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) have improved outcomes in a variety of adult cancers and are prescribed with increasing frequency across oncology. However, patterns of off‐label use of ICI in pediatrics remain unclear. Methods: This is a single‐institution, retrospective cohort study evaluating off‐label ICI use in pediatric and young adult patients with cancer treated at our institution from 2014 to 2022. Response was based on clinician assessment derived from clinical records. Immune‐related adverse events (iRAEs) were classified according to CTCAE v5.0. Results: We identified 50 unique patients treated with off‐label ICI (28 with solid tumors, 20 with central nervous system (CNS) tumors, 2 with hematologic malignancies). At time of ICI initiation, only five patients (10%) had localized disease, and all but one patient was treated in the relapsed/refractory setting. All patients were treated with the FDA‐approved weight‐based dosing recommendations. Overall, there was disease control in 21 patients (42%), with best response including one complete response (melanoma), two partial responses (high‐grade glioma, CNS nongerminomatous germ cell tumor), and 18 patients with stable disease. Forty‐four patients (88%) eventually experienced disease progression. Among 22 patients (44%) experiencing iRAEs, 10 (20%) had a grade ≥3 irAE, 12 (24%) required corticosteroids, and 14 (28%) required ICI discontinuation. irAE occurrence was associated with significantly improved progression‐free survival (HR 0.35; 95% CI: 0.18 to 0.68; p = 0.002) and overall survival (HR 0.33; 95% CI: 0.17 to 0.66; p = 0.002). Conclusions: At our institution, ICI was most commonly prescribed in the relapsed/refractory setting to patients with metastatic disease. The treatment was generally well‐tolerated in the pediatric population. The overall response rate was low, and the majority of patients eventually experienced disease progression. A few patients, however, had durable treatment responses. Further studies are needed to identify which pediatric patients are most likely to benefit from ICI. [ABSTRACT FROM AUTHOR]

Aims: To assess the extent of off‐label drug use and the occurrence of suspected adverse drug reactions (ADRs) among paediatric patients in Italian hospitals. Methods: We conducted a 2‐year prospective cohort study across 22 Italian hospital wards from September 2020 to September 2022. As part of the surveillance project, we performed a 6‐month retrieval of all reported ADRs and evaluated all drug prescriptions for their possible off‐label use. Following an educational project on pharmacovigilance addressed to healthcare professionals in participating wards, the same data collection was performed. Results: Among the 892 patients included in the study, 64% were admitted to paediatric wards and 36% to neonatal wards. Fifty per cent of all drugs prescribed were used off‐label and mainly concerned the administration of a different dose from the one authorized. In neonatal wards, off‐label prescriptions occurred slightly more often, with antibacterials being the most frequently used off‐label drugs. A total of 35 reports of suspected ADRs were collected, five before the educational project and 30 afterwards. Based on product licence, 10 of the total 35 reports concerned at least one off‐label drug use. Conclusions: The off‐label use of drugs in treating paediatric patients was extensive in Italian hospitals. Regulatory interventions are needed to promote the use of drugs based on the latest available literature and improve ADR reporting on children. Paediatric indications and dosages of the drugs most commonly used in children should be supported by appropriate ad hoc studies. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are increasingly prescribed to children and adolescents worldwide, but little is known about reasons for prescribing. We aimed to examine patterns of paediatric antipsychotic prescribing in Australian primary care services in 2011 and 2017, including diagnoses, sociodemographic characteristics, off‐label prescribing, and psychotropic co‐prescribing. Methods: Retrospective analysis of electronic health records (EHRs) using a large Australian general practice database (MedicineInsight). Diagnoses of mental disorders were extracted from EHRs and associated with antipsychotic prescriptions within the same calendar year for three age‐groups: 0–9, 10–14, and 15–18‐year‐olds. Results: In 2017, children/adolescents with mental health diagnoses were more likely to be prescribed antipsychotics (2.9% of 27,412 patients) than in 2011 (2.0% of 8418 patients; absolute difference +0.9, 95% CI + 0.5, +1.4). The likelihood was greater for patients with bipolar disorders (21.6% vs. 41.5%), eating disorders (1.1% vs. 7.2%), and autism without behavioural problems (3.7% vs. 6.1%). Depression/anxiety (adjusted 26.8% of patients 2011; 30.8% 2017) was the most common diagnosis associated with antipsychotics in both years. Most antipsychotics were prescribed off‐label (69.8% 2011; 79.7% 2017; absolute difference +9.8, 95% CI + 1.54, +18.4). Off‐label prescribing increased most among those aged 15–18‐years, females, and patients living in outer regional/remote/very remote communities and the most disadvantaged areas. The three most frequently prescribed antipsychotics in both years were risperidone, quetiapine, and olanzapine. Psychotropic co‐prescribing among patients receiving antipsychotic prescriptions was approximately 69% in both years. Conclusions: Prescribing antipsychotics for mental health diagnoses to children/adolescents attending Australian general practices was more frequent in 2017 than 2011, and most commonly associated with depression/anxiety diagnoses. In both years, most prescribing was off‐label. The majority of patients were co‐prescribed other classes of psychotropics along with antipsychotics. [ABSTRACT FROM AUTHOR]

Many common drugs have not been registered for use in children. Therefore, they are sometimes prescribed as unlicensed or off-label. This study, performed at the Department of Paediatrics, University Hospital Olomouc, Czech Republic, evaluated off-label and unlicensed prescriptions. A similar study, conducted in 2013 by the same authors (P. Matalová – maiden name P. Langerová), showed that the number of off-label and unlicensed prescriptions was relatively low, compared to other studies. The goal of this study was to compare the frequency of off-label and unlicensed drug prescriptions, and to assess whether these prescriptions have declined. [ABSTRACT FROM AUTHOR]

Objective: The objective of this article is to present a decision aid in the form of a flowchart, designed to assist psychiatrists in navigating the challenges of off-label medication use. This tool is believed to be the only one currently available that combines guidance from medical indemnity insurers, RANZCP guidelines, CATG frameworks, and relevant legislation to provide a practical guide for everyday psychiatric practice. Conclusions: There are clinical, legal, ethical, and financial considerations to take into account each time an off-label prescription is ordered. There is no legal barrier to prevent psychiatrists from prescribing off-label in Australia and New Zealand. The medication should be utilised if it is in the best interests of the patient. However, practitioners must be able to defend the rationale for their off-label medication use with evidence of sound quality. Off-label use medication use can lead to improved patient outcomes and quality of life. On the other hand, poor practice in off-label prescribing can result in adverse events, patient harm, legal implications, and damage to professional reputation. By evaluating available evidence, considering patient characteristics, obtaining informed consent, and documenting the rationale for off-label use, clinical decision-making can be enhanced whilst mitigating the risks associated with off-label prescribing. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is approved for moderate‐severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real‐world data because providers have limited practical experience with this recently approved therapy. Objectives: To describe the real‐world effectiveness and safety in patients aged <12 years with moderate‐severe AD currently receiving or previously having received dupilumab. Methods: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off‐label for dupilumab due to their age. Results: Sixty three pediatric patients (37 males) with moderate‐to‐severe AD were included; the mean age was 6.4 years old (range: 2–11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI‐75% and 71% (34/48) achieved EASI‐90. EASI‐75 and EASI‐90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. Conclusions: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging. [ABSTRACT FROM AUTHOR]

Although it was originally developed and approved for the treatment of various psychiatric conditions, such as schizophrenia and bipolar I disorder, recent studies have identified the role of olanzapine in the treatment of intensive care unit (ICU)-related delirium and nausea and vomiting. Unfortunately, olanzapine is currently only indicated to be administered via the intramuscular (IM) route or enteral route, limiting the opportunity of its use in certain pediatric patients. IM injections are typically avoided in pediatrics whenever possible, and it is not uncommon for pediatric patients, especially those in an ICU setting, to be restricted to nothing by mouth. Studies in the adult population have demonstrated both safety and efficacy for the administration of reconstituted olanzapine powder by the intravenous (IV) route, which would provide an ideal administration route for pediatric patients unable to receive IM or enteral administration. We report a case series of 4 pediatric patients who received at least 1 dose of IV olanzapine. All 4 patients reported a positive response from the medication and no safety concerns were noted. [ABSTRACT FROM AUTHOR]

Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians' experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits. Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known: • Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. • Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New: • Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit. • The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion. [ABSTRACT FROM AUTHOR]

Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. Implications: In the light of the current imbalance between gammaglobulins' demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) have become an indispensable part of clinical practice; however, off-label use of these agents is unknown. We aimed to define the patterns of off-label use of ICIs in a nationwide sample of patients. Methods: The online database (Reçetem) was retrospectively searched for off-label use cases related to ICIs approved during a 6-month period. Adult patients with metastatic solid tumors were included. Ethics approval was obtained. Reasons for off-label use were recorded in eight categories and cases were assessed for adherence to current guidelines. Statistical analysis was performed with GNU PSPP version 1.5.3. Results: Five hundred seventy-seven reasons for use were recorded for 538 cases related to 527 patients (67.5% male). Non-small-cell lung cancer (NSCLC) (35.9%) was the most common cancer type. Nivolumab (49%), pembrolizumab (25.5%), and atezolizumab (25%) were commonly used. The top reason for off-label use was lack of approval for the cancer type (37.1%), followed by use beyond the approved treatment line (21%). Nivolumab was more frequently used than atezolizumab and/or pembrolizumab in patients with malignant melanoma, kidney cancer, head and neck cancer, and hepatocellular carcinoma (Chi-square goodness-of-fit test, p < 0.001). The guideline adherence rate was 60.5%. Conclusion: Off-label use of ICIs was primarily related to (NSCLC), and most patients were treatment-naïve in contrast to the acceptance that off-label use results from exhausted treatment options. Lack of approval is a significant reason for the off-label use of ICIs. [ABSTRACT FROM AUTHOR]

Aims: The aim of this research is to study the prevalence of prescribing medicines for off‐label (OL) use and unlicensed (UL) medicines for children during hospitalization in 2021 and to assess changes compared with 2011. Methods: The study included all patients aged <18 years who were treated in the neonatal intensive care unit (NICU) or general paediatric ward of Kuopio University Hospital (KUH), Finland, during 4 weeks in April and May 2021. Their background data and daily information on medicine prescriptions were collected from patient records. The prescriptions were classified as OL, UL or on‐label/approved. The type of OL category was defined. Results: Altogether, 165 children aged 0–17 years (median 3.2 years) were treated in the paediatric wards (46 in the NICU and 119 in the general ward). In total, 1402 prescriptions were made for 153 children (93%). The proportion of OL and UL prescriptions decreased significantly from 55% in 2011 to 45% (age‐adjusted proportion) in 2021 (P <.001). The proportion of patients receiving at least 1 UL medicine prescription decreased from 53% in 2011 to 30% (age‐adjusted proportion) in 2021 (P <.001). About 76% of hospitalized children were still prescribed either OL prescription or UL medicine in 2021. Conclusion: The prescriptions for OL use and UL medicines were less prevalent in 2021 than 2011, but still a majority of hospitalized children were prescribed either medicine for OL use or UL medicine in 2021. This indicates a persisting need for approved medicines in children suggesting that revision of EU Paediatric Regulation 2007 is necessary. [ABSTRACT FROM AUTHOR]

With the increasing costs of drug development, repurposing of low‐cost medicines for new indications has never been more important. However, there are multiple barriers to repurposing, particularly for off‐patent medicines, and limited incentives for the pharmaceutical industry to sponsor registration and public subsidy listing. Here, we explore these barriers and their consequences and provide examples of successful repurposing strategies. [ABSTRACT FROM AUTHOR]

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk–benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy's approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs. [ABSTRACT FROM AUTHOR]

Denosumab is a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) that significantly inhibits osteoclast activity and has been approved to treat osteoporosis, giant cell tumor of bone, and prophylactic as well as therapeutic entities for bone metastasis. However, the imbalance of RANKL/RANK/OPG has also been implicated in the pathogenesis of several other rare bone diseases and tumor-like disorders, including aneurysmal bone cyst, fibrous dysplasia of bone, and Langerhans cell histiocytosis. Nevertheless, there have been various clinical reports although these diseases have not been approved for indications. The review aims to summarize the available evidence for the off-label use of denosumab in metabolic bone diseases and tumor-like disorders and provide a reference for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder is prevalent globally and in Kenya, and is associated with significant health and socio-economic consequences. Despite this, available pharmacological treatment options are limited. Recent evidence indicates that intravenous (IV) ketamine can be beneficial for the treatment of alcohol use disorder, but is yet to be approved for this indication. Further, little has been done to describe the use of IV ketamine for alcohol use disorder in Africa. The goal of this paper, is to: 1) describe the steps we took to obtain approval and prepare for off-label use of IV ketamine for patients with alcohol use disorder at the second largest hospital in Kenya, and 2) describe the presentation and outcomes of the first patient who received IV ketamine for severe alcohol use disorder at the hospital. Case presentation: In preparing for the off-label use of ketamine for alcohol use disorder, we brought together a multi-disciplinary team of clinicians including psychiatrists, pharmacists, ethicists, anesthetists, and members of the drug and therapeutics committee, to spearhead the process. The team developed a protocol for administering IV ketamine for alcohol use disorder that took into account ethical and safety issues. The national drug regulatory authority, the Pharmacy and Poison's Board, reviewed and approved the protocol. Our first patient was a 39-year-old African male with severe alcohol use disorder and comorbid tobacco use disorder and bipolar disorder. The patient had attended in-patient treatment for alcohol use disorder six times and each time had relapsed between one to four months after discharge. On two occasions, the patient had relapsed while on optimal doses of oral and implant naltrexone. The patient received IV ketamine infusion at a dose of 0.71 mg/kg. The patient relapsed within one week of receiving IV ketamine while on naltrexone, mood stabilizers, and nicotine replacement therapy. Discussion & conclusions: This case report describes for the first time the use of IV ketamine for alcohol use disorder in Africa. Findings will be useful in informing future research and in guiding other clinicians interested in administering IV ketamine for patients with alcohol use disorder. [ABSTRACT FROM AUTHOR]

Introduction: Off-label prescribing is defined as using medications outside conditions of the marketing authorisation including their licensed indications, dosage, age and route. Atopic dermatitis (AD) is the most common chronic skin condition in children which can be related to a high level of off-label prescribing. Aim: To investigate the frequency of off-label prescribing and the medications involved in relation to indications and age in paediatric patients hospitalized for atopic dermatitis in a paediatric dermatology ward in 2019. Material and methods: One hundred and seventy-five consecutive discharge letters of patients were analysed regarding gender, age and medications used during hospital stay and prescribed on discharge. Each medication was checked against the licensed age and indications. Results: Altogether 564 medications were prescribed, including 289 topical and 275 systemic ones with 278 prescribed off-label (49.1%). Out of 289 topical medications, 113 (39.1%) were prescribed off-label regarding indications and 34 (11.76%) regarding the age of the patients. In the systemic medications group, 96 (34.53%) were prescribed off-label as AD was not a registered indication and 35 (12.73%) as the age of the patients was outside the marketing authorization. The most frequent medications prescribed off-label were antihistamines, antibiotics and corticosteroids. Conclusions: Prescribing off-label in paediatric population is a common practice. Both topical and systemic medications are frequently used in AD patients off-label, therefore doctors should be familiar with the pitfalls of prescribing beyond the licensed indications and age. [ABSTRACT FROM AUTHOR]

Introduction: Clinical experience, as well as the results of real-world data analysis point to the need for developing a model for the care of patients with drug-resistant depression, which could lead to improved access to effective and safe treatment. Scientific studies carried out to date have unequivocally documented the mode of action of ketamine and identified factors which can influence the efficacy of single infusions of ketamine for depression as well as in cases of affective bipolar disorder. Material and method: Case report including a review of national and international literature and an analysis of the case in the light Polish of EU law. Discussion: The use of ketamine in the treatment of drug-resistant depression raises question regarding its legal qualification, in particular whether such treatment can be characterized as a medical experiment. Conclusions: In the light of international publications, which confirm the validity of the method described above, one might assume that the treatment could be qualified as off-label use of a medicine, but not as a medical experiment as it is understood in the legislation (art. 21 ZawLekU). However, given the nature of this treatment, its qualification as off-label use is not the only one possible and others cannot be immediately ruled out. [ABSTRACT FROM AUTHOR]

(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label. [ABSTRACT FROM AUTHOR]

Objective: Quetiapine use at standard doses has been associated with hyperglycemia and dyslipidemia. However, whether even frequently prescribed low‐dose quetiapine results in significant metabolic disturbances remains unclear. Thus, this study aimed to investigate the association between off‐label, low‐dose quetiapine and changes in glycosylated hemoglobin (HbA1c) levels/lipid parameters. Methods: We identified new users of low‐dose quetiapine (≤50 mg tablets) in Denmark 2008–2018 with measurements of HbA1c, total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), or fasting triglycerides (fTG) within 365 days before and after quetiapine initiation. Mixed‐effects linear regression models were used to estimate coefficients (β) with 95% confidence intervals (95%CIs) for change in cardiometabolic parameters after quetiapine initiation. Inverse probability weighting was used to mitigate selection bias. Higher doses of quetiapine (>50 mg) were included in sensitivity analyses. Results: Among 106,711 eligible new low‐dose quetiapine users (median age = 45 years, females = 55%), low‐dose quetiapine initiation was associated with increased fTG (β = 1.049[95%CI:1.027–1.072]) and decreased HDL‐C (β = 0.982[0.978–0.986]). Although HbA1c did not change significantly and TC and LDL‐C even decreased considering all subjects, all three metabolic parameters increased significantly among individuals with normal pre‐quetiapine initiation levels. The adverse metabolic effect of quetiapine on HbA1c, TC, LDL‐C, and HDL‐C was dose‐dependent, which was not the case for fTG. Conclusions: Low‐dose quetiapine was associated with a significant increase in fTG and decreases in HDL‐C in all subjects, as well as with significant increases in HbA1c, TC, and LDL‐C among those with normal baseline values. The risk of metabolic worsening with quetiapine was dose‐dependent, except for fTG. [ABSTRACT FROM AUTHOR]

With advances in drug development and our understanding of the pathophysiology of skin disease, biologic medications have emerged as powerful management tools for dermatologists. While biologics have most often been used in the management of psoriasis, they are being used off-label for the management of a variety of other immune-mediated skin diseases with overlapping molecular targets. This narrative review focuses on the novel and off-label use of biologic medications for the management of hidradenitis suppurativa (HS), pyoderma gangrenosum (PG), lichen planus (LP), and seborrheic dermatitis (SD). Review of the literature revealed that IL-17, IL-23, and tumor necrosis factor (TNF) inhibitors were being used across a variety of immune-mediated skin pathologies with variable efficacy, among other targeted biologics. While biologics were generally safe in the treatment of primary immune-mediated skin disorders, paradoxical disease eruptions were noted with biologic use and were theorized to occur owing to immune dysregulation and cytokine imbalance. While numerous case reports show promise for the use of biologics in immune-mediated skin pathologies, the variable efficacy and safety reported warrants more thorough investigations of the role of these targeted medications in comprehensive disease management. [ABSTRACT FROM AUTHOR]

At the beginning of the COVID‐19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID‐19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off‐label for the treatment of COVID‐19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases—9.97%—with COVID‐19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID‐19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision‐related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off‐label use in the treatment of COVID‐19 disease. [ABSTRACT FROM AUTHOR]

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit–risk assessment. [ABSTRACT FROM AUTHOR]

Background: Although several meta‐analyses have examined the effects of off‐label underdosing of nonvitamin K antagonist oral anticoagulants (NOACs) compared with their recommended doses in patients with atrial fibrillation (AF), they combined different kinds of NOACs in their primary analyses. Herein, we first conducted a meta‐analysis to separately assess the effects of off‐label underdosing versus on‐label dosing of four individual NOACs on adverse outcomes in the AF population. Methods: The PubMed and Embase database were systemically searched until November 2021 to identify the relevant studies. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by utilizing a random‐effects model. Results: A total of nine studies with 144,797 patients taking NOACs were included in the meta‐analysis. In the pooled analysis, off‐label underdosing of rivaroxaban was related to an increased risk of stroke or systemic embolism (HR = 1.31, 95% CI 1.05–1.63; p =.02), whereas off‐label underdosing of apixaban was associated with a higher risk of all‐cause death (HR = 1.21, 95% CI 1.05–1.40; p =.01). When comparing off‐label underdosing versus on‐label dosing of dabigatran or edoxaban, no differences were found in the primary and secondary clinical outcomes. Conclusion: Off‐label underdosing of rivaroxaban may increase the risk of stroke or systematic embolism, whereas off‐label underdosing of apixaban may heighten the incidence of all‐cause death. [ABSTRACT FROM AUTHOR]

The lack of medicines containing drug information leaflets considering the treatment of pediatric patients is a problem frequently observed in hospitals, especially in the pediatric and neonatal intensive care unit (ICU) sectors. It is known that, for a treatment to be considered safe and effective, a series of clinical studies are necessary; however, a low number of these studies involving children are reported, mainly due to ethical issues that make conducting them difficult. Thus, few drugs prove to be suitable for treating these patients, making it necessary to resort to using off-label and unlicensed drugs. Drugs are classified as off-label when their use differs from their approved specifications, in turn, unlicensed products are classified in this way due to not having approval for marketing in the country or do not have proof of safety and efficacy. Preparation of organized study protocols, reporting information to parents and the child in a clear and objective way, bringing researchers and parents closer to establish a relationship of trust and conducting research at moments when the family is available are important strategies to facilitate conducting clinical trials. [ABSTRACT FROM AUTHOR]

The second‐generation antipsychotic quetiapine is commonly used off‐label for its anxiolytic and hypnotic properties. However, quetiapine is associated with problematic side‐effects. We used Danish Medicinal Product Statistics and a 20% random sample of the Danish population's prescription fills (2001–2020) to describe the utilization of quetiapine and proportion of various prescriber types (general practitioner [GP], specialist in private practice, hospital physician and other prescribers) both in connection to first‐time and subsequent prescriptions. In 2020, 92% of all quetiapine was dispensed outside hospitals and the average daily dispensed quantity of quetiapine per user corresponded to 100 mg/user/d. A GP issued 53% of first‐time prescriptions and 75% of subsequent prescriptions for quetiapine in 2020. The proportion of quetiapine prescriptions issued by GPs varied by age group—from 14% among 0–17‐year‐olds to 93% among the ≥80‐year‐olds. Future initiatives on the rational use of quetiapine and related drugs, especially among adults, should target GPs. [ABSTRACT FROM AUTHOR]

Background: Given increasing community-based and off-label use of ketamine for psychiatric indications, we examined current informed consent processes from a convenience sample of outpatient ketamine clinics to identify areas of congruence with current evidence and opportunities for growth.Methods: Using a rubric developed from existing practice guidelines, we conducted an exploratory analysis of informed consent documents (IC-Docs) from 23 American clinics offering ketamine as a psychiatric treatment. Domains assessed included clinical content, procedures, and syntax.Results: Participating clinics (23/288) varied widely in their constitution, training, and services provided. We found that IC-Docs addressed a majority of consent elements, though did so variably on an item-level. Areas for improvement included communication around long-term adverse effects, treatment alternatives, medical/psychiatric evaluation prior to treatment, medical/psychological support during treatment, adjunctive psychological interventions, and subjective/dissociative-type effects. All forms were limited by poor readability.Limitations: Our study was limited by convenience sampling along with possible underestimation of verbal consent processes.Conclusions: As ketamine continues to emerge as a psychiatric intervention, both patients and providers will benefit from a deliberate consent process informed by scientific, ethical, and pragmatic factors toward the goal of shared decision-making regarding treatment. [ABSTRACT FROM AUTHOR]

Ustekinumab is approved for the treatment of psoriasis and Crohn's disease. Because many dermatological conditions are due to immune-mediated development, ustekinumab may be effective in other conditions. A systematic review of the off-label uses of ustekinumab, as well as on-label adverse effect, was performed, reporting on clinical improvement. MEDLINE, Embase, Web of Science, and Cochrane databases were searched for studies regarding ustekinumab treatment of rativa (HS), lichen planus (LP), pyoderma gangrenosum (PG), pityriasis rubra pilaris (PRP), cutalopecia areata (AA), atopic dermatitis (AD), Bechet's disease, bullous pemphigoid (BP), hidradenitis suppuaneous sarcoidosis, cutaneous systemic lupus erythematosus (SLE), and vitiligo. Descriptive statistics were performed. 74 articles of 4596 screened were included, and reported on 212 patients receiving ustekinumab treatment. Across all studies, ustekinumab showed promise in treating patients: AA (10/12 patients; 83.3% improvement), AD (28/74 patients; 37.8% improvement), HS (42/52 patients; 80.8% improvement), and PRP (25/27 patients; 92.6% improvement), among others. Adverse events were noted with the use of ustekinumab, including development of AA (four patients), AD (three patients), and BP (four patients), among others. Ustekinumab can be a promising option for patients with dermatological conditions refractory to traditional therapies. Adverse events must be monitored in certain patients. [ABSTRACT FROM AUTHOR]

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns. [ABSTRACT FROM AUTHOR]

If an authorized drug is prescribed for a use that is not described in the Summary of Product Characteristics, this is defined as 'off-label use.' Methotrexate is often used off-label for dermatological indications. Off-label use is permitted if physicians can justify the treatment based on scientific evidence available to them. Our objective here was therefore to summarize the evidence for the effectiveness, efficacy, and safety of the dermatological off-label use of methotrexate in a systematic review. We searched MEDLINE, EMBASE, and CENTRAL for studies for evidence on the effectiveness, efficacy, and safety of the off-label use of methotrexate in dermatological indications up to November 2019. We used the GRADE system to rate the quality of the evidence. The search retrieved 34,583 hits of which 3566 were selected after the title and abstract screening. After the full-text screening, 143 studies were included, which involved 3688 patients in total. We found low-quality evidence for the effectiveness, efficacy, and safety of the off-label use of methotrexate in 31 dermatological diseases. To optimize the quality of evidence to support off-label use, we need high-quality studies in which well-characterized patients are treated with standardized treatments regimens using well-validated outcomes relevant to patients and physicians. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the current preferences of ophthalmologists for the treatment of macular edema and age-related macular degeneration (AMD) and to evaluate off-label use of bevacizumab in Turkey. Materials and Methods: All members of the Turkish Ophthalmological Association were contacted by e-mail to complete an anonymous, 47-question internet-based survey. The second part of the survey (questions 36-47) was evaluated. Results: When current legal regulations were considered, ophthalmologists used bevacizumab as the first-line agent in patients with diabetic macular edema (DME), AMD, and retinal vein occlusion (RVO) (58.25%, 55.89%, and 52.29%, respectively). When economic and legal constraints were disregarded, the participants' preference for bevacizumab in the treatment of DME, AMD, and RVO decreased (11.64%, 10.58%, and 10.93%, respectively). Approximately three-quarters (75.75%) of ophthalmologists stated that dispensing multiple syringes from a single bevacizumab bottle could increase the risk of endophthalmitis. Most participants (93.68%) did not feel legally safe from harm caused by off-label bevacizumab use. However, 66.43% of ophthalmologists stated that bevacizumab is as effective as other anti-vascular endothelial growth factor (anti-VEGF) drugs. Conclusion: Bevacizumab is widely used as a first-line treatment for all indications of anti-VEGF use in the current reimbursement conditions, which preclude the right of ophthalmologists to treat according to their own preferences. [ABSTRACT FROM AUTHOR]

Background & Objective: This study aimed to assess the clinical effectiveness of Hydroxychloroquine Sulfate (200 mg orally 8 hourlies thrice a day for 5 days), oseltamivir (75 mg orally twice a day for 5 days), and Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in seven groups). Methods & Analysis: An adaptive design is deployed, set within a comprehensive cohort study, to permit flexibility in fast-changing clinical and public health scenario. Primary outcomes include turning the test negative for coronavirus nucliec acid and in bringing about clinical improvement on day 7 of follow-up on a seven-point ordinal scale. The randomized study will recruit participants of either gender above 18 years of age who will test positive for SARS-CoV-2 on Quantitative Reverse Transcription Polymerase Chain Reaction (PCR). Pregnant or lactating females, and those with severe respiratory distress, or with serious comorbidities will be excluded. Randomization will be done maintaining concealment of allocation sequence using a computer-generated random number list. The sample size will be subjected to periodic reviews by National Data Safety and Monitoring Board. Ethics and Dissemination: The trial is approved by the National Bioethics Committee (No.4-87/NBC-471-COVID-19-05/20/) and institutional Ethical Review Committee. This clinical trial conducted under Good Clinical Practice is expected to inform patients clinical guidelines for the use of these drugs in newly diagnosed with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Immunoglobulin E (IgE) and mast cells play a key role in various allergic diseases. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved the control of these diseases and ushered in a new era in the treatment of severe allergic conditions. Long-term experience with omalizumab in severe allergic asthma has confirmed its effectiveness and safety, reducing the symptoms and incidence of severe exacerbations in patients. In addition to treating severe asthma, Omalizumab has been approved for the treatment of chronic spontaneous urticaria (CSU), and although the mechanisms underlying the action of omalizumab in CSU are not fully understood, almost 90% of CSU patients show complete or partial response to omalizumab treatment. Omalizumab has also recently been approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of a study of omalizumab in inadequately controlled severe hay fever treated with antihistamines and nasal corticosteroids. In recent years, there have been a number of scientific publications showing the successful off-label use of omalizumab in diseases in which IgE plays a key role such as allergic rhinitis, allergic bronchopulmonary aspergillosis, anaphylaxis, keratoconjunctivitis, food allergy, drug allergy, non-atopic asthma, mastocytosis, atopic dermatitis, nasal polyps, Churg-Strauss syndrome, eosinophilic otitis media, chronic rhinosinusitis, bullous pemphigoid, systemic lupus and contact dermatitis. Its safe use in pregnant women with asthma, as well as the concomitant use of omalizumab and allergen-specific immunotherapy, has already been confirmed. Therefore, the potential for omalizumab in other chronic conditions should be considered. [ABSTRACT FROM AUTHOR]

Ruxolitinib is a Janus kinase (JAK) inhibitor that is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease. Its use in treating various dermatologic diseases has been a topic of growing interest due to its favorable safety profile and targeted inhibition of several cytokines that perpetuate inflammatory skin conditions. The PubMed/MEDLINE and ClinicalTrials.gov databases were searched for literature on off-label uses of ruxolitinib in dermatology and ongoing trials studying its safety and efficacy. There is randomized controlled trial (RCT) evidence for the successful use of ruxolitinib in treating alopecia, atopic dermatitis, and psoriasis, with ongoing RCTs for its use in vitiligo. Smaller studies have confirmed the success of ruxolitinib in treating conditions such as dermatomyositis and hypereosinophilic syndrome, among others. No serious adverse effects were reported with the use of ruxolitinib in dermatology, but further research is needed to determine its efficacy, delivery route, and optimal dosing for treating dermatologic conditions. [ABSTRACT FROM AUTHOR]

Introduction: Many efforts have been made to stimulate clinical trials (CTs) in pediatrics but most of the drugs are still authorized only in adults and used off-label in the pediatric population. Aim: To assess how widespread is the off-label prescription in Italy and to identify areas of unmet medical need by applying a model for the systematic collection and analysis of data. Methods: A study was performed using 2015 data from the Italian Medicines Utilization Monitoring Centre Health Database (OsMed). A study sample of 3,726,583 pediatric patients, was considered. Cardiovascular drugs were selected for this study. Assessment of the off-label use, the analysis of the pharmacovigilance signals, a bibliographic research and the analysis of ongoing CTs were carried out. Results: In 2015, 8,544 pediatric patients received treatment with a cardiovascular drug. Angiotensin converting enzyme inhibitors (ACE-I) followed by beta blockers agents are the most prescribed molecules. Eight molecules were selected and an in-depth analysis conducted. The PhV network showed only one record of adverse reaction as off-label in 2015. The results show several therapeutic areas of use in pediatrics. Conclusion: Off-label in pediatrics is largely widespread in Europe and US and our results show it is also present in Italy. Molecules selected are used off-label for therapeutic areas such as oncologic, hematological and rare diseases. Results of pharmacovigilance suggests underreporting. The analysis carried out in this study could be an open track for a systematic monitoring activity and of interest for prescribers, pediatricians and other healthcare professionals during the clinical practice. [ABSTRACT FROM AUTHOR]

Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions. The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations. Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions. Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role. [ABSTRACT FROM AUTHOR]

BACKGROUND: Governmental regulations of drug registration and licensing are not always followed by healthcare providers. OBJECTIVE: To explore the global research growth and patterns on systemic use of off-label and unlicensed drugs to gain knowledge about the magnitude of the problem and the main research themes encountered in this field. METHODS: SciVerse Scopus was searched for papers on off-label and unlicensed drug use from 1990 until December 31, 2020, without any language limitations. A bibliometric methodology was adopted to present the following indicators: top-cited documents, the most productive countries, top active journals, international research collaboration, the most frequent author keywords, and research themes. RESULTS: The search query returned 1320 papers with an h-index of 66, published in 721 different journals. The Hospital Pharmacy journal ranked first (n = 43, 3.3%). In total, 5777 authors (median = 3) from 85 different countries contributed to the retrieved papers. The USA (n = 381, 28.9%) ranked first, followed distantly by Germany and Italy. The percentage of documents with international authors for active countries was from 8.8% for China to 42.3% for the Netherlands. The most frequent author keyword next to off-label was children/pediatrics. The keyword unlicensed was less frequently encountered than that for off-label. Major research themes in the retrieved papers focused on off-label drug use in hospitalized children/pediatrics, biological drugs such as rituximab and rFVIIa, psychiatric disorders, regulations, and questionnaire-based knowledge/attitude studies among community pharmacists and physicians. CONCLUSIONS: Research activity on off-label drug use has witnessed a general increase in the past two decades. The major research theme was off-label drug use in hospitalized children/pediatrics/neonates. The USA and certain European countries made a major contribution to this field. [ABSTRACT FROM AUTHOR]

Botulinum toxin is a neurotoxic protein produced by Clostridium botulinum, the bacterium responsible for botulism. Botulinum toxin was first used for therapeutic indications in the 1970s for the treatment of strabismus. With greater understanding of its underlying physiology and safety profile, the use of botulinum toxin has now expanded to a range of cosmetic and medical indications. We performed a systematic review of current literature on the applications of botulinum toxin on off‐label esthetic uses. Electronic databases were searched for original published studies including randomized trials, observational or cohort studies, as well as relevant case reports. To add to the body of evidence, our review summarizes and synthesizes key study characteristics, results, and level of evidence for each use case. Although the body of evidence remains weak, there is increasing support for the use of botulinum toxin in emerging off‐label esthetic uses of botulinum toxin in dermatology. [ABSTRACT FROM AUTHOR]

Compte tenu des contraintes éthiques, scientifiques et économiques, la plupart des psychotropes mis sur le marché ne sont pas étudiés chez l'enfant. Ce qui explique le nombre restreint de psychotropes possédant l'autorisation de mise sur le marché (AMM) chez la population pédiatrique. Devant ce constat le prescripteur est souvent confronté au problème de la prescription hors-AMM. Cette étude visait à décrire la prévalence des prescriptions hors-AMM des médicaments psychotropes chez l'enfant et l'adolescent dans une unité de pédopsychiatrie. Une étude transversale du contenu des ordonnances prescrites a été menée au sein du service de pédopsychiatrie du Centre hospitalier universitaire IBN Rochd de Casablanca, Maroc, incluant tous les patients âgés de 1 à 18 ans recevant un traitement médical avec des antidépresseurs, des antipsychotiques, des benzodiazépines, et des antiépileptiques. Nous avons inclus un total de 186 lignes de prescriptions. Les principaux constats étaient que 44 % de toutes les prescriptions de psychotropes étaient hors-AMM, et 40,6 % des patients ont reçu au moins 1 médicament hors-AMM. La principale situation de prescription hors-AMM était la prescription dans une tranche d'âge inadaptée 63,9 %, ce qui signifie que le médicament n'a pas été approuvé pour le groupe d'âge du patient. Nous avons trouvé dans cette étude que 45,4 % des prescriptions d'antipsychotiques étaient hors-AMM, et les taux hors-AMM d'anxiolytiques, d'antidépresseurs et d'hypnotiques étaient respectivement 6,6 %, 48 % et 100 %. La co-prescription de 2 médicaments psychotropes ou plus par patient était très fréquente (86,2 %). Cette étude a révélé une utilisation fréquente des prescriptions hors-AMM lors du traitement des enfants et des adolescents avec des médicaments psychotropes. Ces résultats confirment la nécessité d'études cliniques prospectives pour améliorer le libellé des médicaments en pédopsychiatrie. Most psychotropic drugs have not been studied in children due to ethical, scientific and economic constraints. This leads to a reduced number of labeled psychotropic drugs for the pediatric population. Recognizing this, the prescriber faces the problem of the off-label prescription. The principal objective of this survey was to assess and document the off-label prescriptions of psychotropic drugs in child and adolescent patients. A cross-sectional study of prescription content was realized within the child psychiatry department at University Hospital Center of Casablanca, Morocco. All subjects aged 1 to 18 years old receiving medical treatment with antipsychotics, antidepressants, benzodiazepines, or anti-epileptics were included. We registered a sum of 186 prescriptions. The rate of off-label prescription was 44%, and 40.6% of patients took no less than one drug prescribed off-label. The main situation of off-label prescription was the prescription in an unsuitable age group with 63.9%. The off-label rates for each class of drugs were: hypnotics 100%; antidepressants 48%, antipsychotics 45.4%; antiepileptics 16.2%; and anxiolytics 6.6%. The prescription of more than one psychotropic drug per patient was frequent 86.2%. Psychotropic drugs in the child psychiatry department are frequently used in off-label prescriptions as shown in this survey. These results confirm the need for prospective clinical studies to improve labeling for drug products used in Child and adolescent psychiatry. [ABSTRACT FROM AUTHOR]

The year 2020 is facing one of the worst public health situations in decades. The world is experiencing a pandemic that has triggered significant challenges to healthcare systems in both high and low‐middle income countries (LMICs). Government policymakers and healthcare personnel are experiencing real‐life ethical dilemmas and are pressed to respond to these situations. Many possible treatments are being investigated, one of which is the use of hydroxychloroquine or chloroquine. These drugs are approved for use by patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, and malaria. The demand for these products has increased, and the stocks are depleting for the patient population for whom the drugs are intended initially. Although both innovator and generic pharmaceutical manufacturers are making plans for increased production, there are challenges with global supply chains disruption and the retention of supplies for local markets. This may cause countries that rely on the importation of pharmaceuticals to be out of stock of supplies for an extended period. There are allegations of off‐label prescribing and hoarding. Pharmacists are the custodians and dispensers of medications and are faced with the task of assessing prescriptions and making decisions about the allocation of these products. This paper seeks to 1) highlight some of the ethical challenges of dispensing hydroxychloroquine by pharmacists during the COVID‐19 pandemic, 2) identify some of the responses to these issues from various regulatory authorities in the USA, and 3) recommend approaches to assist pharmacists in their decision‐making process, especially in LMICs. [ABSTRACT FROM AUTHOR]

Background and study aims: Lumen-apposing stents (LAMS) are approved to treat peripancreatic collections and for gallbladder and bile duct drainage. Over the last years, LAMS have also been used for off-label indications including gastrojejunostomy, gastro-gastrostomy and drainage of postsurgical collections. We aimed to analyze indications, technical/clinical success rates and complications of all LAMS placed over the last 2 years. Patients and methods: Data from 61 consecutive LAMS (Hot Axios, Boston Scientific) in 57 patients were analyzed. Technical success was defined as successful deployment of the LAMS in the desired position. Clinical success was defined as follows: for pancreatic collections: resolution without the need for non-endoscopic interventions; for choledochoduodenostomy: ≥ 50% drop in baseline serum bilirubin within 2 weeks AND patient can receive chemotherapy if indicated; for gastrojejunostomy: resolution of gastric outlet obstruction and successful re-initiation of oral intake; for gastro-gastrostomy: successful endoscopic access to the excluded stomach; for gallbladder or postsurgical collection drainage: resolution of sepsis. Results: Indications were drainage of peripancreatic collections in 24 cases (39.3%), choledochoduodenostomy in 13 (21.3%), gastrojejunostomy in 6 (9.8%), gastro-gastrostomy in 13 (21.3%), gallbladder drainage in 1 (1.6%) and postsurgical collection drainage in 4 (6.6%). Overall technical and clinical success rates were high (57/61; 93.4% and 54/61; 88.5%, respectively). Clinical success rate for non-approved indications was 95.6% (22/23 cases). Complications occurred in 13 patients (21.3%, 4 serious). Conclusions: LAMS are increasingly used in interventional endoscopy. In our cohort, more than one third of LAMS are placed for off-label indications, with a high success rate and acceptable complication rate. [ABSTRACT FROM AUTHOR]

Primary osteoporosis is rare in children and adolescents and its optimal pharmacological management is uncertain. Bisphosphonates are commonly used while denosumab has only been administered to a few children with osteogenesis imperfecta. We studied a treatment-naïve 13.5-year-old boy with severe osteoporosis and multiple vertebral deformities who presented with back pain and difficulty in walking. Causes of secondary osteoporosis were excluded and there were no abnormalities in genes known to cause bone fragility. He was treated with denosumab 60 mg subcutaneously every 3 months for 30 months, and he was pain-free within 6 weeks after the first injection. Lumbar spine BMD and femoral neck BMD increased with treatment by 65.6% and 25.3%, respectively, and deformed vertebrae regained their normal shape; linear growth was not impaired. During the second year of treatment, transient hypercalcemia (maximum 3.09 mmol/l) before the denosumab injection was observed. In conclusion, denosumab was highly effective in this case of primary pediatric osteoporosis, with remarkable clinical and radiological response. Transient hypercalcemia was probably due to amplification of the effect of growth spurt and puberty on bone remodeling by the transient, short-term discontinuation of the drug. Furthermore, our data suggest that mobilization of calcium from treatment-induced sclerotic transverse lines in bone metaphyses may contribute to the development of hypercalcemia. [ABSTRACT FROM AUTHOR]