Search Results (42)

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

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

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

Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet’s disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet’s disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes. 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

Background: Dalbavancin is a long-acting lipoglycopeptide, approved for treatment of skin and skin structure infections. Its PK/PD profile and safety allow for short hospital stays even in the case of difficult-to-treat infections requiring long courses of therapy, e.g., osteomyelitis, cardiovascular, and prosthetic infections. Objectives: We aimed to evaluate the safety and efficacy of dalbavancin in real life settings for both in-label and off-label indications. Methods: retrospective evaluation of all consecutive patients treated with dalbavancin at our site between May 2017 and September 2021. Results: A total of 100 patients treated with dalbavancin and followed up for 6 months after treatment (58% male; median age 63.5 years, median Charlson Comorbidity Index CCI = 2.7, 28% inpatients) were included with the following indications: acute bacterial skin and skin structure infections (22%), bone and prosthetic infections (57%), and cardiovascular infections (19%). Infections were caused by MSSA (30%), MRSA (5%), MR-CoNS (20%), and Streptococcus spp. (8%). In 32 cases, no isolate was obtained. The average number of infusions was 5 (s.d. = 3). Neither ensuing alteration of renal function nor neutropenia or thrombocytopenia were observed during treatment and follow-up. Two self-limiting skin rashes occurred. The overall clinical success rate was 84%—91% for registered and 82% for unregistered indications. The prescription of higher loading doses was the only predictor independently associated with better outcomes in multivariate models (OR: 5.2, 95%CI: 1.5–17.9, p < 0.01). Conclusions: Dalbavancin proved to be effective for skin and skin structure infections, as well as for difficult-to-treat infections in highly comorbid patients. Regarding tolerability, our results support the use of dalbavancin for long-lasting treatments of deep-seated infections. 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

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

(1) Background: The escalating use of opioids contributes to social, health, and economic crises. In Spain, a notable surge in the medical prescription of opioids in recent years has been observed. The aim of this work was to assess the consumption rate of fentanyl, categorised by the different administration routes, in Primary Care in the province of Salamanca (Spain) spanning the years 2011 to 2022, and to compare it with the national trend and with data from the US. (2) Methods: Doses per inhabitant per day (DHD) were calculated, and interannual variations, as well as consumption rates, were subject to thorough analysis. (3) Results: The prevalence of fentanyl use in Salamanca has doubled from 1.21 DHD in 2011 to 2.56 DHD in 2022, with the transdermal system (TD) as the predominant administration route. This upward trajectory mirrors the national trend, yet the rise in fentanyl use is markedly lower than the reported data in the US. This finding may be attributed to an ageing population and potentially inappropriate fentanyl prescriptions, i.e., for the management of chronic non-cancer pain and other off-label prescriptions. (4) Conclusions: The use of fentanyl in Salamanca, particularly through transdermal systems, doubled from 2011 to 2022, aligning with the national trend. Preventive measures are imperative to prevent fentanyl misuse and moderate the observed escalation in consumption rates. 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

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug. Full article