Search Results (55)

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

Antimicrobial resistance (AMR) is a growing global concern, influenced by antibiotic use in both human and veterinary medicine, especially in companion animals. In low- and middle-income countries, regulatory oversight on veterinary prescriptions is often limited, creating gaps that can accelerate AMR. This study aimed to characterize the use of antibiotics approved for human use that are prescribed by veterinarians for companion animals in Brazil, a country representative of broader regulatory challenges. We conducted a retrospective analysis of five years (2017–2021) of national sales data recorded by the National System for the Management of Controlled Products (SNGPC), maintained by the Brazilian Health Regulatory Agency (ANVISA). A total of 789,893 veterinary antibiotic prescriptions were analyzed over the five-year period, providing a comprehensive overview of prescribing patterns. The dataset included all oral and injectable antibiotics purchased in human pharmacies with veterinary prescriptions. Data wrangling and cleaning procedures were applied to extract information on volume, antibiotic classes, seasonal variation, and regional distribution. The results revealed a predominance of penicillins, first- and second-generation cephalosporins, and a marked increase in macrolide use, especially azithromycin. Notable regional disparities were observed, with the southeastern region leading in prescription volume. The findings, particularly the disproportionate use of azithromycin and the marked regional disparities, highlight the need for targeted monitoring policies and a stricter regulation of off-label antibiotic use in veterinary medicine. They also offer insights applicable to other countries facing similar AMR threats due to limited surveillance and regulatory frameworks. Full article

Background: Fungal infections, particularly among immunocompromised individuals, present significant challenges due to rising incidence rates, treatment costs, and increasing resistance to antifungal agents. This study evaluates trends in antifungal use among Medicaid beneficiaries, focusing on prescribing patterns, costs, and pricing to optimize therapy. Methods: Using the national Medicaid outpatient pharmacy claims data collected by the US Center of Medicare and Medicaid Services, a retrospective drug utilization analysis was conducted for antifungal medications from 2009 to 2023. Antifungal medications were categorized based on therapeutic use. The study examined annual utilization, reimbursement, and pricing trends, along with the market share. Results: Overall Medicaid utilization of superficial fungal infections’ (SFIs’) medications increased from 3.95 million prescriptions in 2009 to 6.16 million in 2023. Nystatin was the most frequently utilized SFI agent, while fluconazole emerged as the most commonly prescribed agent for invasive fungal infections (IFIs). In 2022, a notable spike occurred in the number of prescriptions for both SFIs and IFIs. Medicaid’s total expenditure on SFI medications rose from USD 121.9 million in 2009 to USD 155 million in 2023, while spending on IFI medications fluctuated substantially, peaking at USD 156.8 million in 2022 before declining to USD 80.7 million in 2023. After being introduced to the market, efinaconazole became the most expensive SFI agent over the years. Isavuconazole, the latest approved IFI medication, demonstrated sustained utilization, reimbursement, and price increases. Conclusions: The substantial rise in antifungal utilization and spending underscores the growing financial burden on Medicaid, emphasizing the need for policy interventions to manage costs and generic drug substitution while ensuring equitable access to these essential treatments. However, this study is limited by the lack of clinical outcome data and information on off-label use. Additionally, reimbursement data may not accurately reflect actual drug prices. Full article

Background/Objectives: Some ophthalmic antibiotics are publicly subsidised in New Zealand (NZ) for off-label use in the ear, however, this utilisation has not previously been described. This study compared the utilisation of ophthalmic chloramphenicol and ciprofloxacin in the eye and ear, among NZ children. Methods: This study involved clinical record review, and included 11,617 prescriptions of ophthalmic chloramphenicol and ciprofloxacin in 2022, for children aged five years or under in Auckland, NZ. Prescriptions of chloramphenicol and ciprofloxacin for eye and ear use were compared by: patient age, gender, ethnicity and socioeconomic deprivation, indication, community or hospital prescribing and number of repeat prescriptions. Statistical analysis was performed using Chi-squared test and multinomial regression. Results: Most ophthalmic ciprofloxacin was used in the ear (84%). In contrast, almost all chloramphenicol was used in the eye (96%). Post-operative use following tympanostomy tube insertion accounted for half of all hospital-prescribed ophthalmic ciprofloxacin used in the ear. Utilisation of chloramphenicol and ciprofloxacin in the eye and ear was similar, with more prescriptions for children aged one year and males, and most children received only one prescription. Māori and Pacific children generally received fewer prescriptions. Pacific children were more likely than Māori children to receive hospital-prescribed ophthalmic ciprofloxacin for use in the ear (adjusted OR 6.7, p = 0.025). Conclusions: These findings highlight the utilisation of ophthalmic ciprofloxacin in the ear in NZ children. These findings will inform decision-making in the public funding of medications, policy development in equitable medication access, and more collaborative efforts to improve antimicrobial use. Full article

Pediatric-onset multiple sclerosis (POMS) is a chronic, immune-mediated disorder that affects the central nervous system in children and adolescents. Approximately 3–10% of MS patients have an onset that occurs before the age of 18. The vast majority of pediatric MS cases are characterized by a relapsing-remitting course with a high burden of disease activity. Pediatric MS patients were historically treated off-label with varying degrees of success. With the approval of many new therapies for adult-onset MS, alternative treatments in pediatric MS have rapidly started to emerge. In this narrative review, we will discuss therapeutic advancements in pediatric multiple sclerosis, including the seminal trials of PARADIGMS, which evaluated fingolimod use in pediatric MS patients, CONNECT (dimethyl fumarate), TERIKIDS (teriflunomide), OPERETTA I (ocrelizumab), and LEMKIDS (alemtuzumab). We will also review the safety and efficacy of different monoclonal antibodies that are commonly prescribed for multiple sclerosis. We will then examine induction versus escalation treatment strategies and conclude with discussions on treatment considerations in POMS patients. Full article

Background/Objectives: Off-label drug use is prevalent in pediatric care, particularly in pediatric palliative care (PPC), due to the scarcity of pediatric-specific formulations and clinical trials. Differences in perception between healthcare professionals regarding off-label prescriptions underscore the complexity of this practice and highlight the need for improved collaboration to optimize therapeutic outcomes. Methods: A cross-sectional observational study was conducted from August to October 2021 at the PPC center of the University Hospital of Padova, Italy. Data were collected from medical records of 169 patients. Off-label prescriptions were independently assessed by two physicians and two clinical pharmacists using respective reference sources. Discrepancies were resolved through consensus. Statistical analyses included the χ²-test for categorical variables and t-tests for continuous data. Results: Among the 993 drug prescriptions analyzed, the pharmacists reported a higher proportion of off-label uses (32.9%) compared to the physicians (18.4%; p < 0.05). After a consensus, 26.5% of the prescriptions were identified as off-label, with 67.9% due to indications, 49.6% due to dosage, and 44.4% due to age discrepancies. Conclusions: This study suggests a high prevalence of off-label prescribing in pediatric palliative care (PPC) and highlights differing professional perspectives, underscoring the potential benefits of exploring standardized protocols and enhanced interdisciplinary collaboration. Enhanced communication between healthcare providers, alongside the development of registries and clinical trials, is essential for improving the safety and efficacy of off-label drug use in pediatric populations. A flexible regulatory framework and customized galenic formulations could further support these goals. Full article

Background/Objectives: This study evaluated the appropriateness of transmucosal immediate-release fentanyl (TIRF) prescriptions in a Madrid emergency room during 2019 and 2022, following a 2018 warning about off-label use. Methods: TIRF prescription in the emergency room search yielded 993 patients in 2019 and 1499 in 2022, of which 140 were randomized for the study, 70 in 2019, and 70 in 2022. Dose appropriateness and indication for TIRF were analyzed according to established criteria. Results: Despite a high prevalence of cancer diagnoses (77.9%, 109/140), only 32.9% (46/140) of patients met the appropriateness criteria pre-hospitalization. This improved to 42.5% (51/120) at discharge, but the change was not statistically significant overall. However, focusing on surviving patients reveals a significant improvement in appropriateness, increasing from 30.83% (37/120) to 42.50% (p = 0.002). This improvement was particularly pronounced in 2022 (p = 0.0269), but not in 2019 (p = 0.0771). Interestingly, appropriateness in patients with prior TIRF prescriptions remained relatively stable from pre-hospitalization (46.75%) to discharge (48.78%). A concerningly high proportion of patients with cancer diagnoses (68.75%) received low-dose opioid therapy (<60 MME) at discharge, and 36.8% of patients over 80 years old were co-prescribed benzodiazepines, contradicting prescribing guidelines. Conclusions: This study found inappropriate TIRF prescriptions were common in an emergency room setting, often due to low pre-hospital opioid doses. While hospitalization improved TIRF appropriateness in survivors, especially in 2022, concerning prescribing practices persisted. This emphasizes the need for better education and interventions to ensure safe and effective TIRF use. Full article

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and is prescribed off-label for several neurological conditions like neuropathic pain, migraines and anxiety. Besides their action on the reuptake of monoaminergic neurotransmitters, tricyclic antidepressants interact with several additional targets that may contribute to either therapeutic or adverse effects. Here, we investigated the effects of amitriptyline on proliferation and autophagy (i.e., an evolutionarily conserved catabolic pathway responsible for the degradation and recycling of cytoplasmic material) in human SH-SY5Y neuroblastoma cell cultures. The dose and time-dependent upregulation of the autophagy marker LC3II and the autophagy receptor p62, with the accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to the amitriptyline. These effects were accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5^−/− MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine, suggesting that they were independent from autophagy modulation. Our findings demonstrate that amitriptyline acts on pathways crucial for cell and tissue homeostasis (i.e., autophagy and proliferation) and pose the basis for further studies on the potential therapeutic application of amitriptyline, as well as the consequences of its use for long-term treatments. Full article

Off-label practice in pediatrics requires relentless engagement from all the health professionals involved. Community pharmacists are the last ones in the prescribing–dispensing chain; therefore, they have the key responsibility of verifying the correctness of a treatment. A cross-sectional study was conducted for assessing the awareness and views of Romanian community pharmacists, regarding off-label drugs in the pediatric population, through a 28-item questionnaire comprising five sections of different topics (general knowledge, frequency of prescribing and dispensing off-label medication, views, and attitudes). The sample size was 236 questionnaires with a response rate of 41.11%. A statistical analysis of the obtained data was performed with GraphPad Prism v.9. The results indicate that 55.1% of the community pharmacists have a good general knowledge and awareness regarding the off-label practice, although the legal frame is unclear. The responses highlight a high frequency of prescribing and request of medication for respiratory conditions (45.3%) and antibiotics (23.5%), with a concerning gap regarding the adverse events related to the off-label treatments (56.7%). A very small percentage of pharmacists (7.1%) contact a fellow healthcare professional when encountering an off-label prescription. In conclusion, in addition to the pharmacist’s conduct towards the best interest of the patient, there is a clear need to improve the doctor–pharmacist collaboration in order to make an off-label treatment successful. Full article

This retrospective study assesses the efficacy and tolerability of anti-calcitonin gene-related peptide (anti-CGRP) therapy in adolescents and young adults (ages 12–21) with migraine and chronic daily headaches unresponsive to standard treatments. Migraines in this demographic significantly impair school performance, self-esteem, psychological well-being, and cognitive health. These young patients are also particularly sensitive to the side effects of conventional medications, which are often prescribed off-label and come with high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels observed during migraines suggest that anti-CGRP therapies, successful in adult populations, may also benefit this younger age group. Over a three-year period, patients at a specialized pediatric headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, and galcanezumab) and small-molecule CGRP receptor antagonists (ubrogepant, rimegepant, and atogepant), administered either alone or in combination with OnabotulinumtoxinA. Data were extracted from the hospital’s electronic medical records, and patient progress was consistently documented using a structured template for each clinic visit. Additional patient satisfaction data were collected via telephone follow-ups and patient message reviews. The study included 23 patients, primarily treated for chronic migraine (CM) (78.3%), with a smaller subset addressing episodic migraine (EM), new daily persistent headaches (NDPHs), and post-traumatic headaches (PTHs). Comprehensive demographic and clinical data, including age, treatment duration, history of preventive treatment failures, and comorbidities like psychiatric conditions and sleep disorders, were collected. Anti-CGRP therapies, particularly when combined with traditional treatments or OnabotulinumtoxinA, resulted in significant improvements: 91.3% of patients experienced reduced migraine duration and intensity, 82.6% reported improvements in other bothersome symptoms, and 73.9% saw an improved response to rescue medications. Additionally, 78.3% of patients reported a reduction in their use of rescue medications per week by more than 50%, and emergency room visits were reduced for 56.5% of patients. Significant reductions in headache days were observed in 82.6% of patients after one month and 87% after three months, with nearly 40% experiencing more than a 50% reduction in both periods. The greatest benefits were observed in patients treated for more than six months. Adverse effects were minimal, with 95.7% of patients reporting no side effects, and patient satisfaction was high, with 69.6% opting to continue treatment. Overall, this study highlights the substantial potential of anti-CGRP therapy in improving outcomes for adolescents and young adults with CM and EM, offering a promising approach for a demographic that faces considerable challenges with conventional treatment options. However, further research is needed to confirm these findings and expand clinical applications in this age group. Full article

Despite reliable evidence of adverse drug effects, the substantially increased prescription rates of proton pump inhibitors (PPIs) remain at a high level. This study analyzed the appropriateness of PPI prescriptions among residents of nursing homes in three regions of Germany. Baseline data of a cluster-randomized controlled trial were used to determine the prevalence of PPI prescriptions, the validity of indications, and the adequacy of the prescribed dosages according to 1. their drug approvals and 2. valid recommendation guidelines. Regression analyses were conducted to assess associated factors. A total of 437 residents in 37 nursing homes were included (mean age 83 ± 9.2 years, 72% women). The PPI prescription prevalence was 44% (n = 193). In 52/193 (27%) there was no adequate indication, and in 54 (39%) of 138 indicated PPI prescriptions it was overdosed. Yet, in only less than one-third (28%) of “adequate” prescriptions, the indication was according to the PPI approvals, whereas the majority (72%) were off-label indications in line with valid guideline recommendations. Non-indicated PPI prescription was associated with the total number of prescribed drugs (OR 1.32; 95% CI 1.18–1.62; p = 0.013). There were no associations with age, level of care dependency, cognitive impairment, prescription of psychotropic drugs, number of chronic diseases, number of physicians’ consultations, or study region. To conclude, in 55%, the high prescription prevalence among residents was either not indicated or overdosed. In total, only 20% (39/193) of cases of PPI use complied with the approved indications. There is a need for quality control of 1. PPI administration in German nursing homes, and 2. of guideline recommendations expanding the off-label PPI use by 72% within the indication scale, predominantly from wide prescription for low-dose ASA. Full article

People with intellectual disabilities (IDs) often present with challenging behaviors (CBs) mostly due to inappropriate environments and mental and physical disorders. Integrative care is recommended to address CBs. However, in clinical practice, psychotropic drugs are often prescribed off-label for CBs, although the effectiveness is unclear, and side effects frequently occur. We conducted a cluster-randomized controlled study to investigate the effect of integrative care provided by a collaboration of an ID specialized mental healthcare team and participants’ own ID service providers’ care team on reducing CBs and inappropriate off-label psychotropic drug prescriptions compared with care as usual. Participants (N = 33, aged 19–81 years) had a moderate, severe, or profound intellectual disability and used off-label psychotropic drugs. The primary outcome measures were the Aberrant Behavior Checklist and the total dose of psychotropic drug prescriptions. At the study endpoint of 40 weeks, we found no effect of the intervention on the total ABC score and on the total dose of psychotropic drug prescriptions. In the intervention group, however, the psychotropic drug dose decreased significantly, while CBs did not change. The small sample size and not-completed interventions due to organizational problems may have affected our findings. This study illustrates the difficulties in the implementation of integrative care. Full article

Background: Children with medical complexity (CMC) often require multiple medications, leading to polypharmacy, which seems to be linked to adverse effects, administration errors, and increased caregiver burden. This study aimed to describe the prevalence of polypharmacy, medication burden, off-label drug use, and associated costs. Methods: Conducted at the Pediatric Palliative Care Center of Padua, Italy, from August to October 2021, this cross-sectional observational study included patients up to 23 years old with at least one prescribed drug. Data were collected from medical records and caregiver interviews. Drug costs were collected from the Italian Medicine Agency. Descriptive statistical analysis was performed. For comparisons among categorical variables, the Chi-square test was used, and for those among continuous variables, the ANOVA test was used. Results: This study analyzed treatment regimens of 169 patients with a median age of 12.5 years (0.3–23). Polypharmacy was present in 52.7% of patients, and medication burden was observed in 44.4%, both varying significantly by primary diagnosis (p < 0.001). The median daily cost per patient was EUR 2.2 (IQR 0.9–7.1), with significant variation among subgroups. Only 34.6% of prescriptions were off-label. Conclusions: polypharmacy and medication burden are frequent among our CMC population, with some differences according to primary diagnosis. Full article

Off-label drug use is prevalent in the pediatric population and represents a patient safety concern. We aimed to identify factors for off-label drug use in our pediatric emergency department (PED). Methods. We performed a retrospective data analysis. All patients aged 0–18 referred to PED from 1 September to 1 October 2022, were included. Further analysis was performed when respiratory tract infections were diagnosed. Data collected: gender, age, triage group, chronic diseases, vital signs, and PED-prescribed treatment (medications, dosages, methods of administration). Statistical analysis used SPSS 28.0, with significance at p < 0.05. Results. Data from 473 patients were analyzed, median age 3.5 years. Chronic diseases were present in 17.1% of children. 387 medications were prescribed, 47.5% being off-label. Off-label treatment was common for external otitis, acute laryngitis, and acute bronchitis (p < 0.001). There was incorrect administration of tobramycin with dexamethasone for otitis (n = 16, 100%) and inappropriate use of salbutamol inhalations by age (34.8%, n = 16). Some medications were given orally instead of injections (ondansetron n = 5, 62.5%; dexamethasone n = 82, 98.7%) or intranasally instead of intravenously (IV) (midazolam n = 7, 87.5%). IV adrenalin was prescribed for inhalations (n = 46). Younger children were more likely to receive off-label treatment (p < 0.001). Conclusion. Our study highlights the widespread issue of off-label and unlicensed drug prescribing in pediatric emergency care. Further research is necessary, because this reliance on off-label prescribing raises concerns about patient safety and compliance, especially given the limited clinical trials and therapeutic options available. Full article