Search Results (116)

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/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments. Full article

This review explores the potential of magistral formulas (MFs) as a viable option to meet the needs of neonates, given the lack of adequate therapies for this vulnerable group. The scientific literature on medicines available for neonates is limited. The physiological differences between neonates and adults make it difficult to formulate these medicines. In addition, there are a variety of difficulties in conducting research on neonates: few clinical trials are performed, and there is frequent use of unauthorized medicines. Pharmacokinetics in neonates was investigated in comparison to adults, and different aspects of the absorption, distribution, metabolism, and excretion were observed. One of the main problems is the different pharmacokinetics between the two populations. It is necessary to promote and allow research related to pediatric drug design, approve a specific authorization for use in age-appropriate dosage forms, and improve the quality and availability of information on drugs. This study focused on the MFs typically used for pediatrics, specifically for neonates, analyzing the pharmaceutical forms currently available and the presence of indications and dosage recommendations of the European Medicines Agency. Medications were classified according to therapeutic group, as antihypertensives, corticosteroids, and antiepileptics. The use of off-label medicines remains high in neonatal intensive care units and in primary healthcare, besides in the preparation of MFs by pharmacists. The shortage of medicines specifically designed and approved for neonates is a serious problem for society. Neonates continue to be treated, on numerous occasions, with off-label medicines. Studies and research should be expanded in this vulnerable population group. Full article

Background: Lateral lumbar or thoracic interbody fusion (LLIF) is increasingly considered for anterior column reconstruction and restoring segmental lordosis in degenerative, infectious, or deformity conditions. Reports about using LLIF with expandable interbody spacers for spine trauma are scarce. Methods: In this retrospective, single-center observational cohort study, we reviewed all patients treated by an expandable LLIF interbody spacer (ELSA^® Expandable Integrated LLIF Spacer, Globus Medical Inc) for trauma indication at our spine center between September 2018 and January 2024. The primary outcome measures were fusion rate at 12 months, change in segmental sagittal Cobb angle, and clinical outcome according to the MacNab criteria. Secondary outcomes included adverse events and complications. Results: We identified n = 21 patients with a mean age of 48.3 (standard deviation (SD) 15.7), 47.6% were female. LLIF was mostly performed at T11/12 (n = 4; 19.1%) and T12/L1 (n = 10; 47.5%). Indications were AO Spine type A2 (n = 4, 19.1%), A3 (n = 14; 66.7%) or A4 fractures (n = 3; 14.3%) with ligamentous (B2-type) in eight (38.1%) and hyperextension (B3-type) injury in one patient (4.8%). Surgery included the release of the anterior longitudinal ligament in four cases (19.1%). Intraoperative AEs were noted in n = 1 (4.8%), postoperative AEs in n = 3 (14.3%) at discharge, n = 4 (19.1%) at three, and n = 2 (9.5%) at twelve months. Segmental sagittal Cobb angle changed from 1.3° (preoperative) to 13.3° at twelve months (p < 0.001). Functional outcome was excellent/good in n = 15 (71.4%; four missing) at 12 months. The fusion rate at the LLIF level was 100% at the 12-month follow-up. Conclusions: LLIF with expandable interbody spacers for spine trauma (off-label use) is safe, promotes solid fusion (100% fusion rate at 12 months), and enables correction of sagittal segmental Cobb angle (mean improvement of 12°), with good or excellent clinical outcomes in most patients (71.4%). Full article

Background/Objectives: Hyoscine butylbromide (HBB) is a spasmolytic drug classified as indispensable by the World Health Organization. While mostly used in adults, it is also approved for use in adolescents and children aged 6 years and older. We have comprehensively reviewed the efficacy and safety of HBB in approved and off-label childhood indications. Results: Childhood studies covered an age range starting as early as 2 days. A randomized controlled trial (RCT) found a similar efficacy compared to paracetamol in the approved indication of abdominal cramps and pain. Among off-label uses, several studies demonstrate efficacy in general anesthesia and various diagnostic procedures, but the largest body of evidence relates to use in childbirth/labor, including 17 RCTs. While these largely focused on efficacy outcomes on the mother, fetal safety outcomes were reported in 12 of these studies, mostly as effects on the APGAR score and/or heart rate. The overall evidence supports safety in infants and children including those younger than the approved use age of 6 years and older. Conclusions: While only limited pediatric efficacy data from RCTs are available in the approved indications, data from thousands of patients in RCTs, case series, and non-randomized trials do not raise concerns on the safety and tolerability of HBB in childhood. Additional dedicated childhood studies, particularly RCTs, on efficacy are recommended. 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

Background/Objectives: Since 28 January 2022, veterinary medicinal products (VMPs) must be used in accordance with the conditions of the marketing authorisation (Regulation (EU) 2019/6, Article 106). This entails further restrictions on therapeutic freedom, for example, with regard to dose deviations. Off-label use is any use of a product that deviates from the Summary of Product Characteristics (SPCs). To date, there are no data available on the type and extent of off-label use on the basis of which the feasibility of the new regulation in Germany can be assessed. Methods: Therefore, a Germany-wide anonymous online survey was conducted as a quantitative cross-sectional study comprising 196 questions according to off-label use in dogs and cats. Results: In quantitative terms, the survey was representative of 358 participants but limited due to the demographic characteristics of the participants. A total of 91.3% (326/357) veterinarians stated that they had used antibiotics off-label. Fusidic acid, chloramphenicol, tylosin, and florfenicol were most frequently reclassified with regard to animal species. Authorised drugs for cats and dogs such as amoxicillin/clavulanic acid, doxycycline, metronidazole, and fluoroquinolones, like enrofloxacin and marbofloxacin, were also used off-label, often with regard to indication and treatment duration. Conclusions: Although there are comparatively many antibacterial preparations available for cats and dogs, off-label use is common practice. In many cases, special circumstances of the individual case justify the off-label use of authorised preparations for cats and dogs. The survey results indicate that some dose revisions are recommended. Guidance for specific indications in cats and dogs could contribute to greater legal certainty in small animal practice with regard to the justification of off-label use. Full article

Off-label treatment is the use of a drug approved for marketing, outside the registration in terms of indication, age group, dose or route of administration. Despite the constant appearance of new preparations on the market, treatment outside the SmPCs guidelines is a current clinical problem. It is believed that it is based on the needs of patients unmet by classical therapy methods. This work focuses on off-label treatment in inflammatory dermatoses such as atopic dermatitis, psoriasis, acne vulgaris and rosacea. Publications on this subject, available on PubMed, Google Scholar and the Cochrane Library, were analyzed in the form of a review, taking into account the mechanisms of action, efficacy and safety of preparations. Based on the literature analysis, it can be concluded that the use of drugs outside the SmPC indications is a common situation in dermatology. However, it is difficult to determine its exact frequency—there is a lack of data on the prevalence of off-label appliances in inflammatory dermatoses from a European perspective. Publications demonstrate varying effectiveness and safety of this form of therapy, depending on the specific preparation. Off-label treatment in dermatology remains an important and current clinical issue that should be explored in further research. Full article

The respiratory epithelium maintains the barrier against inhaled harmful agents. When barrier failure occurs, as in several respiratory diseases, acute or chronic inflammation leading to destructive effects and exacerbations can occur. Macrolides are used to treat a spectrum of infections but are also known for off-label use. Some macrolides, particularly azithromycin (AZM), reduce exacerbations in chronic obstructive pulmonary disease (COPD), whereby its efficacy is thought to be due to its effects on inflammation and oxidative stress. In vitro data indicate that AZM reduces epithelial barrier failure, evidenced by increased transepithelial electrical resistance (TEER). Here, we compared the effects of macrolides on differentiation and barrier integrity in VA10 cells, a bronchial epithelial cell line for 14 and 21 days. Erythromycin, clarithromycin, roxithromycin, AZM, solithromycin, and tobramycin (an aminoglycoside) were analyzed using RNA sequencing, barrier integrity assays, and immunostaining to evaluate effects on the epithelium. All macrolides affected the gene expression of pathways involved in epithelial-to-mesenchymal transition, metabolism, and immunomodulation. Treatment with AZM, clarithromycin, and erythromycin raised TEER and induced phospholipid retention. AZM treatment was distinct in terms of enhancement of the epithelial barrier, retention of phospholipids, vesicle build-up, and its effect on gene sets related to keratinocyte differentiation and establishment of skin barrier. Full article

Background/Objectives: Spironolactone (SP) has been used off-label in pediatrics since its approval, but its use is challenged by limited pharmacokinetic (PK) data in adults and especially in children. Methods: Physiologically based pharmacokinetic (PBPK) models for SP and its active metabolites, canrenone (CAN) and 7α thio-methyl spironolactone (TMS), in adults were developed. These models aim to enhance understanding of SP’s PK and provide a basis for predicting PK and optimizing SP dosing in infants and neonates. Given SP’s complex metabolism, we assumed complete conversion to CAN and TMS by CES1 enzymes, fitting CES1-mediated metabolism to the parent-metabolite model using PK data. We incorporated ontogeny for CES1 and CYP3A4 and other age-related physiological changes into the model to anticipate PK in the pediatric population. Results: The PBPK models for SP, CAN, and TMS accurately captured the observed PK data in healthy adults across various dosing regimens, including the impact of food on drug exposure. The pediatric PBPK model was evaluated using PK data from infants and neonates. Simulations indicate that 2.5 mg/kg in 6-month to 2-year infants and 2 mg/kg in 1–6-months infants matched the total unbound systemic exposure equivalent to the standard recommended daily maintenance dose of 100 mg in adults for treating edema. Conclusions: The developed PBPK model provides valuable insights for dosing decisions and optimizing therapeutic outcomes, especially in populations where clinical studies are challenging. Full article

Background: The advent of biosimilars has revolutionized the management of conditions like rheumatoid arthritis by offering cost-effective alternatives to expensive biologics. Objectives: This study aims to compare the post-marketing safety profiles of biosimilars used in rheumatology with their respective reference products (RPs). Methods: Data were retrieved from EudraVigilance for biosimilars of adalimumab, etanercept, infliximab, and rituximab, and compared with their RPs. Our analysis focused on biosimilars authorized before 2021, using data from January 2021 to December 2023. We conducted a descriptive analysis of suspected adverse events, categorized using the Medical Dictionary for Regulatory Activities, and performed a comparative analysis using the reporting odds ratio to identify potential safety signals of disproportionate reporting. Results: We analyzed 75,327 reports, identifying 566,249 drug–event pairs. The results indicate that biosimilars have safety profiles largely comparable to their RPs. Female patients predominated in the reports, representing 69.4% of RPs and 56.9% of biosimilars. Notably, biosimilars demonstrated higher reporting rates for non-serious suspected adverse drug events (AEs), such as injection site pain, arthralgia, and fatigue. Specific AEs, including drug ineffectiveness and off-label use, were more frequent for infliximab and etanercept biosimilars, possibly reflecting real-world usage patterns and nocebo effects. Serious AEs, including malignancies and immunological reactions, were also noted, underscoring the necessity for ongoing monitoring. Conclusions: Our findings suggest that biosimilars are safe alternatives to RPs, contributing to significant healthcare cost savings in the EU. This study underscores the need for ongoing pharmacovigilance and long-term safety research to validate the clinical use of biosimilars in rheumatology. Full article

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and interaction, along with restricted and repetitive patterns of behavior, interests, or activities. ASD encompasses a wide spectrum of clinical presentations and functional impairments, ranging from mild to severe. Despite its prevalence, the underlying physiopathological mechanisms of ASD remain largely unknown, resulting in a lack of effective targeted therapeutic interventions, contributing to significant financial and emotional burdens on affected families and the healthcare system. Emerging evidence suggests that dysfunction in the tetrahydrobiopterin (BH4) pathway may impair the activity of monoaminergic and nitric oxide (NO)-dependent neurons in individuals with ASD. To explore this potential mechanism, we conducted a systematic review to analyze such impairments to gather information on whether the off-label use of BH4 could represent a novel pharmacological approach for managing ASD. Following the PRISMA 2020 guidelines, we systematically reviewed the literature from four databases: PubMed, Virtual Health Library, Cochrane Library, and SciELO, from January 1967 to December 2021. The quality of the included studies was assessed using the Newcastle–Ottawa scale. The inclusion criteria for this systematic review focused on identifying articles published in English that contained the following keywords, used in various combinations: autism, ASD, autism spectrum disorder, BH4, tetrahydrobiopterin, neopterin, NO, nitric oxide. The analysis was performed between December 2020 and December 2021. The collected data demonstrated that BH4 metabolism was altered in individuals with ASD. Lower levels of BH4 were reported in biological samples from ASD-affected individuals compared to age- and sex-matched controls. Additionally, neopterin levels were elevated in plasma and urine, but decreased in cerebrospinal fluid, while nitric oxide levels were consistently reported to be higher across studies. Treatment with BH4 has shown potential in improving ASD-related symptoms. The reported increase in neopterin in biological fluids indicates inflammation, while the reduction in BH4 levels suggests a potential shift in its metabolic role. Specifically, BH4 may be diverted from its primary role in neurotransmitter synthesis to function as an antioxidant or to perpetuate inflammation through NO production. Given that BH4 is a critical cofactor in monoaminergic neurotransmission, its dysfunction highlights the molecule’s therapeutic potential. BH4, already FDA-approved for other conditions, emerges as a promising off-label candidate to alleviate ASD symptomatology. 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