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ABSTRACT Background Methods Results Conclusion Off‐label drug use (OLDU) is a common practice in health care institutions, and numerous guidance documents have been developed to guide the management of OLDU in China. This scoping review aims to compare these documents and identify existing issues.PubMed, EMbase, three Chinese databases, the National Public Service Platform for Standards Information and the official websites of pharmaceutical‐related associations were searched to identify guidance documents relevant to the management of OLDU for Chinese health care institutions. We extracted and compared the recommended practices for various aspects of OLDU management, including management systems, organizational structure, prerequisites for OLDU, approval processes, evidence‐based evaluation, informed consent, and other related aspects.A total of 16 guidance documents were included, comprising 12 expert consensuses, 2 practice guidelines, and 2 group standards. Only six documents provide specific requirements for the establishment of management systems. Management of OLDU requires involvement from multiple departments or committees, yet only a few documents explicitly delineate the supervisory authority, and the responsibilities of the parties involved. These documents also show significant disparities in their approval process, evidence‐based evaluation, and informed consent recommendations. Furthermore, only a minority of the documents provide specific requirements for training and assessments focused on OLDU and improving adverse reaction monitoring.These guidance documents differ significantly in their specific recommendations for the management of OLDU and lack sufficient emphasis on certain critical aspects. It may be beneficial for health administrative authorities to promote the development of unified national guidelines. [ABSTRACT FROM AUTHOR]

Drug package inserts are a crucial foundation for clinical medication practices and serve as the legal basis for guiding rational drug use and ensuring patient safety and efficacy. As rare disease treatments evolve, current package inserts often need to meet the clinical requirements for treating such conditions, frequently resulting in off-label drug use. This consensus is derived from discussions between Guangdong Pharmaceutical Association Hematologic Rare Diseases Group experts. The consensus aims to provide a framework and reference for the clinical application of off-label drug use in treating rare hematologic diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To establish the pharmaceutical care pathways of nanoparticle albumin bound paclitaxel ( nab-PTX), so as to provide reference for clinical rational drug use. METHODS: Data of patients who used nab-PTX from Jan. 2020 to Jun. 2023 in the hospital were retrospectively analyzed and evaluated. The pharmaceutical care pathways of rational use of nab-PTX was established based on the instructions of nab-PTX, evidence-based medicine, and the real-world data of nab-PTX use in the hospital. RESULTS: Data analysis of 279 patients included in this study showed that 42 cases of metastatic breast were in line with the drug indications of nab-PTX, and 237 cases (84. 9%) were off-label. There were 209 off-label cases with evidence-based medical evidence (including cervical cancer, pancreatic cancer, stomach cancer, non-small cell lung cancer, nasopharyngeal cancer, ovarian cancer or fallopian tube cancer, esophageal cancer, endometrial cancer, and cholangiocarcinoma), which were evaluated as rational drug use. However, some off-label cases (oral cancer, mediastinal tumor, bone carcinoma, soft-tissue carcinoma, prostatic cancer, and malignant duodenal neoplasm) were evaluated as irrational due to insufficient evidence-based medical evidence. The most common adverse drug reactions of nab-PTX were myelosuppression and peripheral neuropathy, which were consistent with the drug instructions. The pharmaceutical care pathways of nab-PTX were established from various aspects, including pre-chemotherapy, chemotherapy, post-chemotherapy and follow-up. CONCLUSIONS: Offlabel drug use of nab-PTX is common, and the management for application of nab-PTX should be strengthened. The development of pharmaceutical care pathways of nab-PTX can improve the work efficiency of pharmacists and ensure the safe and rational drug use of cancer patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Drug package inserts are a crucial foundation for clinical medication practices and serve as the legal basis for guiding rational drug use and ensuring patient safety and efficacy. As rare disease treatments evolve, current package inserts often need to meet the clinical requirements for treating such conditions, frequently resulting in off-label drug use. This consensus is derived from discussions between Guangdong Pharmaceutical Association Hematologic Rare Diseases Group experts. The consensus aims to provide a framework and reference for the clinical application of off-label drug use in treating rare hematologic diseases.

Relevance. Off-label use of medications is a common practice in clinical settings. To address the growing interest in this issue, the International Society for Pharmacoepidemiology (ISPE) has developed new general guidelines for off-label prescribing in clinical practice that emphasize the importance of evidence-based medicine and promote transparent communication between healthcare professionals and patients.Objective. The aim of this work was to analyze and present key trends for optimizing off-label prescribing decisions based on the ISPE recommendations (2023).Results. The report highlights five main recommendations: seeking strong scientific evidence, including the use of real-world data; using expert knowledge to evaluate and summarize evidence; developing recommendations with rigorous consistency; aligning the use of off-label medications with research; and strengthening collaboration among regulators, researchers, clinicians, and the pharmaceutical industry.Conclusions. A comprehensive approach is required to address the problem of off-label use of medicines. Implementation of these initiatives will reduce the risks associated with off-label use, generate sustainable scientific evidence, and improve the quality of patient care.

OBJECTIVE: To investigate the management status of off-label drug use in 146 medical institutions, so as to provide reference for improving the management level of off-label drug use. METHODS: Off-label drug use management in 146 medical institutions was investigated by questionnaire survey, including 104 tertiary hospitals and 42 secondary hospitals. Basic situation, management status, existing problems and successful experience were statistically analyzed. RESULTS: There were different degrees of off-label drug use in 146 medical institutions, of which 125 (85. 62%) carried out off-label drug use management. The management measures included establishment of management system (125 / 125, 100. 00%), formulation of off-label drug use catalogue (106 / 125, 84. 80%), and supervision for rationality of use process ( 112 / 125, 89. 60%). Totally 97. 26% ( 142 cases) of the respondents believed that sufficient evidence-based basis was the premise of off-label drug use. The proportion of medical institutions with sufficient evidence of off-label drug use was “about 50%” in 33. 56% (49 institutions), “almost all” in 34. 25% (50 institutions), and “few” in 30. 14% (44 institutions). Off-label drug use management had problems such as clinicians’ lack of cooperation / attention, non-use in accordance with prescribed procedures ( 116 / 146, 79. 45%), widespread off-label phenomenon, and difficulty in comprehensive management ( 73 / 146, 50. 00%). Management of off-label drug use can be improved by multi-department cooperation, clear responsibilities, hierarchical management according to the level of evidence or risk, and the introduction of information management. CONCLUSIONS: The phenomenon of off-label drug use is widespread, and medical institutions have made some success in the management of off-label drug use, yet there are also difficulties. Successful experience should be promoted to improve the management level of off-label drug use in medical institutions, so as to standardize the behavior of off-label drug use. [ABSTRACT FROM AUTHOR]

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.

Background: Thrombopoietin receptor agonists (TPO-RAs) have been widely used to treat thrombocytopenia, however, a scientometric profile of TPO-RAs research is lacking. Methods: This study uses VOSviewer, CiteSpace, and R software to provide an overview of current research, highlight study hotspots, and predict future research directions of TPO-RAs. Results: One thousand seven hundred and nineteen relevant studies from 1993 to 2022 with 43962 citations were identified from the Web of Science Core Collection. Over three decades, the USA has been leading TPO-RAs publications. Industries and academic institutions have been actively involved in TPO-RAs research, with funding provided by pharmaceutical companies and public funding bodies. The most productive and cited journals are British Journal of Hematology and Blood, respectively. When author keywords were categorised into three clusters, i.e., cluster 1 (immune thrombocytopenic purpura (ITP)), cluster 2 (avatrombopag, lusutrombopag, and thrombocytopenia), and cluster 3 (TPO-RAs for ITP and off-label drug use), ITP was found to be the current research hotspot, while oral TPO-RAs and licensed or unlicensed drug indications of thrombocytopenic diseases require further investigation. Conclusion: This study has generated the knowledge map of TPO-RAs, which provides a dynamic roadmap for future research in this field.

OBJECTIVE: To investigate the clinical application characteristics of ulinastatin, so as to provide reference and basis for standardizing its clinical application and updating drug instructions. METHODS: Clinical data of 3 032 inpatients with ulinastatin from Jan. 2021 to Jun. 2022 in the hospital information system of Yantai Yuhuangding Hospital was retrospectively collected, the basic data and clinical medication information were statistically analyzed. RESULTS: The majority of 3 032 patients with ulinastatin were male, accounting for 59. 96% ( 1 818 cases), with an average age of ( 60. 92 ± 14. 28) years. The top three departments ranked by case number of ulinastatin were cardiac surgery, gastroenterology and hepatobiliary surgery. A total of 742 cases (24. 47%) met the indications of drug instructions, the rest were off-label drug use, and there were 1 977 cases (65. 20%) of off-label drug use with higher level evidence-based evidence. The single dose, solvent and frequency of ulinastatin were rational, and no related adverse drug reactions occurred. The average drug utilization index of ulinastatin in the hospital was 0. 59 (<1), the overall dosage was rational. CONCLUSIONS: The off-label use of ulinastatin is common, and relevant measures should be taken to standardize the clinical application. For application with sufficient evidencebased evidence and common clinical use, it is recommended that drug manufacturers update and revise the drug inserts in a timely manner. [ABSTRACT FROM AUTHOR]

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OBJECTIVE: To perform clinical comprehensive evaluation of total glucosides of paeony capsules in the treatment of recurrent oral ulcer based on evidence-based evidence, so as to provide reference for clinical rational drug use. METHODS: Wangfang Data, CNKI, CBM, PubMed, Embase, the Cochrane Library, the International Health Technology Assessment Network, the International Health Technology Assessment Association and other websites were systematically retrieved to collect clinical research, pharmacoeconomic research, safety evaluation and other data of total glucosides of paeony capsules in the treatment of recurrent oral ulcer (the search deadline was from database establishment to Nov. 30th, 2022). The quality of literature and its methodology were evaluated and analyzed. RESULTS: A total of 15 articles were included, including 12 clinical studies and 3 safety evaluations, pharmacoeconomics studies were not included. The total glucoside of paeony capsules has certain advantages in the treatment of recurrent oral ulcer in improving the total effective rate, shortening the ulcer healing time, reducing pain score, improving the level of inflammatory factors, improving immune function, and promoting the long-term curative effect. The safety study results showed that the total glucoside of paeony capsules had higher safety and lower incidence of adverse drug reactions in clinical use, and combined treatment with other western drugs could effectively reduce the occurrence of adverse drug reactions and enhance patient compliance. Results of drug accessibility evaluation showed that total glucosides of paeony capsules had good availability, affordability, convenience and acceptability in the treatment of recurrent oral ulcer. CONCLUSIONS: Total glucosides of paeony capsules can significantly improve the total effective rate, improve the quality of life of patients, relieve pain, and has higher safety in the treatment of recurrent oral ulcer, yet there is a lack of literature on pharmacoeconomics. In the future, more standardized clinical observation and related pharmacoeconomics research should be further carried out to supplement evidence of higher quality. [ABSTRACT FROM AUTHOR]

The subject of the use of medicinal products containing “medical marijuana” during the therapy of terminal patients has been the subject of extensive discussion until recently. Currently, such action is legal, but questions still arise not so much about the possibility of using medical marijuana in the treatment of terminally ill patients, but about the implementation of off-label use treatment. The analysis of the applicable legal provisions, views of scholars in the field, and the case law allow us to conclude that treatment involving medical marijuana inconsistently with the SmPC (Summary of Product Characteristics) is an acceptable action that should not be equated with a therapeutic experiment in the strict sense. The above is confirmed by the admissibility of using marijuana raw materials as the basis for the preparation of a pharmacy-compounded (prescription) medicine. The production of pharmacy-compounded drugs requires the use of pharmaceutical raw materials, the amount and composition of which depend on an independent decision of the person prescribing the medicine. The admissibility of any composition of the contents of a pharmacy-compounded drug containing medical marijuana speaks for the admissibility of its use in any way. The above leads to adoption of similar requirements in relation to pre-made drugs containing marijuana. Regardless of the admissibility of using medical marijuana outside the SmPC or in the form of a compounded drug, medical marijuana treatment is the implementation of the patient’s right to treat pain and receive health services in accordance with the current state of medical knowledge.

Abstract Background Off-label drug use exists widely in medical practice and is also an area which easily triggers controversy between patients and medical institutions. Previous studies have identified the reasons why off-label drug use long exists. However, there is no multidimensional analysis on real judicial precedents about off-label drug use. This study aimed to investigate the dispute points on off-label drug use based on real cases in China, and proposed suggestions based on newly-leased Physicians Law. Methods Our study is a retrospective study with all the 35 judicial precedents on off-label drug use extracted from China Judgments Online from 2014 to 2019. This study mainly used the methods of statistical analysis, inferential analysis, exemplification, literature summarization and comparative analysis. Results According to the analysis of the 35 precedents of jurisdictions from 11 different aspects, it can be seen that the second-instance and retrial rates of this kind of cases are high, and the disputes between patients and medical institutions are fierce. In judicial practice of off-label drug use, medical institutions are determined whether to bear civil liability according to the constituent elements of medical tort liability: the rate of medical institutions’ bearing liability for off-label drug use is not high, and medical institutions are not directly identified as infringing acts and they don’t bear tort liability. The clear provisions about off-label drug use in Law of the People’s Republic of China on Physicians which was implemented in March 2022 confirm this at the legislative level. Conclusions By analyzing the current judicial practice of China’s off-label drug use cases, and summarizing the dispute points between medical institution and patients, the constituent elements of tort liability, and the rules of evidence etc., suggestions are proposed to further regulate off-label drug use and promote safe and rational drug use.

Off-label drug use （OLDU） is extremely common worldwide. However， if the safety of OLDU cannot be supported by sufficient evidence-based medicine， it will lead to legal disputes when it causes adverse events. OLDU should be considered with cautions especially for vulnerable populations， such as the elderly， children and pregnant women. In this article， according to off-lab contents and up-to-date guidelines， clinical trials and other evidence-based medicine at home and abroad， OLDU medication guidelines of immunotherapy drugs and COVID-19 antiviral drugs for COVID-19 therapy were collected and compiled. OLDU guidelines were formulated especially for the vulnerable populations， aiming to provide reference for clinical drug requirement and promote rational drug use.

OBJECTIVE: To summarize the situation of new antineoplastic prescription special review in the hospital, so as to promote rational use of drugs. METHODS: Retrospective analysis was performed on the special review of new antineoplastic prescription in the hospital from 2018 to 2021, and the review results were analyzed and summarized. RESULTS: From 2018 to 2021, there were 48 reviews on new antineoplastic drugs. A total of 4 800 prescriptions were selected, and 4 578 prescriptions were rational, with rational rate of 95. 38%. Of the 222 irrational prescriptions, 197 prescriptions were non-standard prescriptions (88. 74%), and the irrational types were “prescribing without clinical diagnosis or incomplete clinical diagnosis”; there were 25 inappropriate prescriptions (11. 26%). A total of 276 prescriptions were involved in off-label drug use, all about indications;among the drugs involved, apatinib had the largest number of off-label drug use prescriptions ( 166 prescriptions, 60. 14%), followed by antirotinib (49 prescriptions, 17. 75%). CONCLUSIONS: According to the current regulations, clinical guidelines and other evidence, constantly improving the review rules and procedures of new antineoplastic drugs will make the prescription more standardized and clinical use more reasonable. [ABSTRACT FROM AUTHOR]

Recent updates in genomic-integrated glioma classification have caused confusion in current clinical practice, as management protocols and health insurance systems are based on evidence from previous diagnostic classifications. The Korean Brain Tumor Society conducted an electronic questionnaire for society members, asking for their ideas on risk group categorization and preferred treatment for each individual diagnosis listed in the new World Health Organization (WHO) classification of gliomas. Additionally, the current off-label drug use (OLDU) protocols for glioma management approved by the Health Insurance Review and Assessment Service (HIRA) in Korea were investigated. A total of 24 responses were collected from 20 major institutes in Korea. A consensus was reached on the dichotomic definition of risk groups for glioma prognosis, using age, performance status, and extent of resection. In selecting management protocols, there was general consistency in decisions according to the WHO grade and the risk group, regardless of the individual diagnosis. As of December 2022, there were 22 OLDU protocols available for the management of gliomas in Korea. The consensus and available options described in this report will be temporarily helpful until there is an accumulation of evidence for effective management under the new classification system for gliomas. [ABSTRACT FROM AUTHOR]

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BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

Background: Off-label drug use exists widely in medical practice and is also an area which easily triggers controversy between patients and medical institutions. Previous studies have identified the reasons why off-label drug use long exists. However, there is no multidimensional analysis on real judicial precedents about off-label drug use. This study aimed to investigate the dispute points on off-label drug use based on real cases in China, and proposed suggestions based on newly-leased Physicians Law. Methods: Our study is a retrospective study with all the 35 judicial precedents on off-label drug use extracted from China Judgments Online from 2014 to 2019. This study mainly used the methods of statistical analysis, inferential analysis, exemplification, literature summarization and comparative analysis. Results: According to the analysis of the 35 precedents of jurisdictions from 11 different aspects, it can be seen that the second-instance and retrial rates of this kind of cases are high, and the disputes between patients and medical institutions are fierce. In judicial practice of off-label drug use, medical institutions are determined whether to bear civil liability according to the constituent elements of medical tort liability: the rate of medical institutions' bearing liability for off-label drug use is not high, and medical institutions are not directly identified as infringing acts and they don't bear tort liability. The clear provisions about off-label drug use in Law of the People's Republic of China on Physicians which was implemented in March 2022 confirm this at the legislative level. Conclusions: By analyzing the current judicial practice of China's off-label drug use cases, and summarizing the dispute points between medical institution and patients, the constituent elements of tort liability, and the rules of evidence etc., suggestions are proposed to further regulate off-label drug use and promote safe and rational drug use. [ABSTRACT FROM AUTHOR]

When a drug has been approved by the regulatory authorities for indications, ages, doses, and routes of administration, but any of them is used for purposes not listed in the permit, it is referred to as off-label drug use. The off-label drug use is often used for patients in vulnerable situations, such as children, the elderly, and cancer patients, who have difficulty in clinical trials for indication and dose determination. Appropriate off-label drug use can lead to the expansion of patients' right to treatment, and systematic monitoring can help identify the current status of drugs used outside the license and ensure the stability of drug use. However, criticism cannot be avoided that there is no consistent and systematic safety management for off-label drug use in Korea because the procedures for off-label drug use of benefits and non-benefit drugs, general drugs and anticancer drugs are different. Therefore, after reviewing the concept and characteristics of off-label drug use, and the current status and problems of the domestic management system, I would like to argue the necessity of preparing decision-making procedures for expert groups and protecting patients' right to self-determination. [ABSTRACT FROM AUTHOR]

Off-label drug use (OLDU) is extremely common worldwide. However, if the safety of OLDU cannot be supported by sufficient evidence-based medicine, it will lead to legal disputes when it causes adverse events. OLDU should be considered with cautions especially for vulnerable populations, such as the elderly, children and pregnant women. In this article, according to off-lab contents and up-to-date guidelines, clinical trials and other evidence-based medicine at home and abroad, OLDU medication guidelines of immunotherapy drugs and COVID-19 antiviral drugs for COVID-19 therapy were collected and compiled. OLDU guidelines were formulated especially for the vulnerable populations, aiming to provide reference for clinical drug requirement and promote rational drug use. [ABSTRACT FROM AUTHOR]

Copyright of Studia Iuridica Lublinensia is the property of Maria Curie-Sklodowska University in Lublin and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166).    Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: • There exist a large number of studies on off-label drug use in children. What is New: • This is the first scoping review of studies on off-label drug use in children. • Off-label use of antipsychotic agents is widely reported. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To assess demographic characteristics in patients with ocular Behçet's disease who use off-label drugs in Turkey. METHODS: The applications for off-label drug use (infliximab, adalimumab, mycophenolat mofetil) from hospitals in Turkey to the Turkish Medicines and Medical Devices Agency from January to December 2013 were evaluated retrospectively. The files of the cases were evaluated in terms of demographic data, previous treatment regimens and reasons for referral. RESULTS: The study included 124 patients who were admitted for off-label drug use. The mean age of the patients was 32.1 +- 7.9 years. While 72.6% of all applications were male, 27.4% were female. Seventy-eight percent of the applicants were from Marmara and Central Anatolia. Infliximab was the most applied off-label drug in ocular Behçet's disease at a rate of 75% in Turkey. When the hospitals that applied were taken, the state universities took the first place with a ratio of 88% and the education and research hospitals came to the fore with a 6.5% rate. DISCUSSION AND CONCLUSION: Examination of demographic data on off-label drug use can be a guide in terms of providing the necessary convenience in legislation in line with drug preferences.

Background: Furosemide has limited indications in the term neonates. Its use in preterm neonates is off-label. Considering the dearth of data, we carried out a retrospective study evaluating the furosemide use and its effects on the electrolyte abnormalities in critically ill neonates. Methods: Critically ill neonates receiving at least one dose of furosemide during their stay in the NICU were recruited. The following details were obtained: demographic characteristics and furosemide details (dose, frequency, route, and duration). Urine output, body weight, serum creatinine, electrolytes (sodium, potassium, calcium, bicarbonate, chloride, and magnesium) during furosemide therapy were extracted. Results: Ninety neonates were recruited. Elevated serum creatinine was observed in 21.1% of the patients, and electrolyte disturbances were observed in 52.2%. Those with electrolyte disturbances had significantly greater cumulative doses compared to those without [5.5 (1– 34) vs 3.9 (0.9– 30.2) mg/kg; p = 0.01]. Cumulative doses adjusted to body-weight were significantly lower in very preterm and extremely preterm neonates compared to late preterm category. A significant area-under-the-curve was observed for the cumulative dose (0.66; 95% CI: 0.54– 0.78; p = 0.01) in predicting the risk of electrolyte abnormalities with a cut-off value of 4 mg/kg. Eight neonates received more than 10 mg/kg cumulative dose of furosemide of which one died. No significant differences were observed between the proportion of neonates with electrolyte disturbances with cumulative furosemide dose above 10 mg/kg (p = 0.3) and with mortality (p = 0.3). Conclusion: We observed that our critically ill neonates received relatively higher cumulative doses of furosemide and electrolyte disturbances were observed in nearly half of the population. A cumulative dose of 4 mg/kg increases the risk of electrolyte abnormalities, particularly in preterm neonates. More diligence in the dose titration coupled with deprescribing and intense monitoring of all the potential adverse effects in this vulnerable population is needed. [ABSTRACT FROM AUTHOR]

Summary: Introduction We analyzed the outcomes of patients with advanced cancers in our institution treated with off-label drugs targeting actionable genomic alteration based on next-generation sequencing who did not qualify for clinical trials. Purposes Our study endpoint was objective tumor response or stable disease at 16 weeks or later after treatment initiation. Methods Sixteen patients were included, 8 treated with immune checkpoint inhibitors targeting PD-L1 expression or TP53 mutations and 8 with other drugs. Tumors were analyzed based on PD-L1 expression, TP53 mutation, MSI, TMB, MMR status, and other targetable alterations. Results Of the 16 patients in the intention-to-treat group, no patients had an objective response after 16 weeks. Eleven patients met the primary study endpoint with stable disease, 8 in the immune checkpoint inhibitors group and 3 in the non-immune checkpoint inhibitors group. Using the log-rank test, the p-value for the difference between groups was 0.008. Conclusions In this study with off-label drugs, immune checkpoint inhibitors targeting TP53 mutations or PD-L1 expression were superior to the other drugs. This suggests the possibility of off-label use of anti-cancer drugs based on next-generation sequencing to be beneficial for advanced cancer patients without other therapeutic options. [ABSTRACT FROM AUTHOR]

Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies. [ABSTRACT FROM AUTHOR]

Objective: Off-label drug use (OLDU) of neurologic diseases is approved by a regulatory authority, the Turkish Medicines and Medical Devices Agency (TMMDA) in Turkey. It was aimed to investigate the most common neurologic drugs relevant to off-label prescribing and the most prescribed diagnosis, demographic and medical characteristics of patients with OLDU applications in Turkey. Materials and Methods: Four years “TMMDA”s electronic OLDU application records, 9,758 applications in total, were evaluated retrospectively. Information regarding patients’ demographic characteristics, diagnoses, ordered drugs, and institutions were evaluated. Results: The most OLDU applications were mostly made in 2015, the majority of which were associated with neurodegenerative diseases. The mean age of the patients was 41.6 years and 65% were female. Some 62.1% of off-label drug application patients’ age range was found as 18-64 years. The most common applications were from the Marmara region with 36% and neurology clinics of university hospitals with 81%. Multiple sclerosis (MS) was the most common diagnosis and the most frequently used group of drugs was disease-modifying drugs used in the treatment of MS. Conclusion: Based on the four-year survey of OLDU applications for adult neurologic patients showed that unlicensed drug prescriptions were high. There are very few studies on the result of OLDU applications in neurology worldwide. We believe that this study will be a guide to neurologists with off-label application processes and the results in our country and will make a significant contribution to the literature.

Apha-1-adrenergic receptor antagonists (α1-blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α1-blocker exposure (before or during hospitalization) and COVID-19 in-hospital mortality. We identified 2,627 men aged 45 or older who were admitted to Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York. Men exposed to α1-blockers (N = 436) were older (median age 73 vs. 64 years, P < 0.001) and more likely to have comorbidities than unexposed men (N = 2,191). Overall, 777 (29.6%) patients died in hospital, and 1,850 (70.4%) were discharged. Notably, we found that α1-blocker exposure was independently associated with improved in-hospital mortality in a multivariable logistic analysis (OR 0.699; 95% CI, 0.498-0.982; P = 0.039) after adjusting for patient demographics, comorbidities, and baseline vitals and labs. The protective effect of α1-blockers was stronger among patients with documented inpatient exposure to α1-blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α1-blocker across age groups: Age 45-65 OR 0.483, 95% CI 0.216-1.081 (P = 0.077); Age 55-75 OR 0.535, 95% CI 0.323-0.885 (P = 0.015); Age 65-89 OR 0.727, 95% CI 0.484-1.092 (P = 0.124). Taken together, clinical trials to assess the therapeutic value of α1-blockers for COVID-19 complications are warranted.

Objective To analyze the current situation of off-label drug use for tic disorder in a tertiary maternity and child hospital, so as to promote clinical safe and rational drug use. Methods Through the hospital information system, the pediatric outpatient prescriptions diagnosed with tic disorder from July 2019 to August 2020 were selected, and the prescriptions of off-label use was evaluated according to the 2020 off-label drug management regulations. Results A total 1 251 pediatric prescriptions diagnosed with tic disorder were collected. The incidence of off-label drug use was 29.58%. The main types of off- label were over-indications and over-age. The main varieties of off-label drug use were risperidone tablets (47.84%) and aripiprazole tablets (43.74%). Conclusion The off-label use of drug for tic disorder in pediatric outpatient department of our hospital is relatively common，and it is necessary to standardize the management of off-label drug use to ensure rational drug use. [ABSTRACT FROM AUTHOR]

Background/aim: Pediatric patients, especially those with rare diseases, represent a population that has a high tendency towards offlabel drug use (OLDU) and needs a more careful practice of pharmacotherapy than in adults. We aimed to investigate biotechnological drug use in children with rare diseases requiring OLDU. Materials and methods: This retrospective study examined all single-diagnosed OLDU applications (n = 5792) for 4992 children (<18- year) in Turkey. Applications of rare diseases were selected, and their descriptive characteristics were examined, including demographic features of patients, biotechnological drug utilization status, and disease categories. The off-label statuses of the drugs at the end of 2020 were also examined. Results: In total, 77.7% (n = 4501) of OLDU applications were made for rare diseases. Biotechnological drug use was higher in rare disease applications than in nonrare diseases (37.9% vs. 19.2%, respectively; p < 0.0001). Canakinumab was the top applied biotechnological drug (73.2%). Compared to that in small-molecule drugs, the mean age of patients was higher in biotechnological drug-containing applications (8.1 ± 5.3 vs. 9.7 ± 4.9, respectively; p < 0.0001). Biotechnological drug use was higher in non neoplastic rare diseases (40.3%) than in neoplastic rare diseases (26.4%), (p < 0.0001). At the end of 2020, the approval status of the off-label indications covered in 2016 was significantly higher for rare (24.4%) vs. nonrare (5.2%, p < 0.0001) diseases and for biotechnological (32.3%) vs. small molecule (13.9%, p < 0.0001) drugs. In total, 87.7% of the drugs would have to be still used in the off-label setting at the end of 2020. Conclusion: It was seen that more than three-quarters of the pediatric OLDU applications are for rare diseases, and the need for biotechnological OLDU in this group is almost 2-fold of small-molecule drug use. While further projected findings imply a higher approval tendency for rare diseases and biotechnological drugs, there seems to be more room for improvement for pediatric drug use. [ABSTRACT FROM AUTHOR]

Abstract Background Off-label drug use is widespread in pediatric drug treatment, and the implementation of guidelines on this topic remains challenging. The objective of this study was to evaluate current practice and awareness of healthcare professionals towards pediatric off-label drug use, as well as the barriers to guideline implementation among pediatric healthcare professionals in Shanghai, China. Methods A validated questionnaire was issued to representatives of pediatricians, pharmacists, nurses and administrators from hospitals with pediatric qualification in Shanghai. Results A total of 679 completed questionnaires from 69 hospitals were included in the analysis. Nearly half (47.9%) of the pediatricians acknowledged that they had prescribed off-label drugs. Most (88.4%) of the pharmacists acknowledged that they had dispensed off-label medicines. The main reason for off-label prescribing was the lack of pediatric dosage information. The most common category of off-label prescribing in children was dosage. Nearly half (42.0%) of the participating hospitals had developed internal protocols for off-label drug use. However, approximately half of the respondents reported that they did not adhere to the guidance and that it had barriers to implementation. Most respondents (84.5%) declared that they were familiar with the term “off-label drug use”. However, the awareness rate of the Chinese Expert Consensus of Pediatric Off-Label Drug Use was low (45.7%). More than half (55.4%) of the respondents declared that they did not adhere to the process proposed in the consensus and that barriers existed for its utilization. Conclusions Pediatric off-label drug use is widespread in Shanghai, China, and barriers exist to the implementation of the guideline. A legally recognized national guideline with a broad scope of application for off-label drug use is urgently needed; at the same time, more education and training on off-label drug use should be provided to targeted healthcare professionals.

Clinical guidelines emphasized that physicians should be cautious when prescribing acid suppressions to infants. Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are not approved for use in infants aged below 2 years in China. We investigated H2RA/PPI use in infants aged below 2 years hospitalized between 1st January 2015 and 31st December 2018 in a Chinese tertiary children's hospital. Our study observed that H2RAs/PPIs were frequently prescribed with a prevalence of 4.4% (7,158/162,192). The frequency of PPI use was over two-fold than that of H2RA use (71.9%, 5,148/7,158; 28.1%, 2,011/7,158). H2RAs/PPIs were commonly used to treat infants without digestive system diseases (57.5%, 4,118/7,158). Further studies are urgently needed to evaluate the effectiveness and safety of H2RAs/PPIs in infants.

OBJECTIVE: To investigate the status of off-label drug use in outpatient department of a stomatological hospital（ hereinafter referred to as "the hospital"), so as to provide reference for improving the level of rational drug use in stomatological hospital. METHODS: Off-label drug use information in outpatient prescriptions of the hospital from Jul. 2019 to Jun. 2020 was collected. PASSPA2 system was used to randomly select outpatient prescriptions according to the rate of 3%. Pareto chart and related rules were used to retrospectively analyze the prescriptions of off-label drug. RESULTS: Totally 5 153 outpatient prescriptions were selected, including 9 444 medical orders. There were 1 393 prescriptions with off-label drug use, and the incidence of off-label drug use was 27. 03%. There were3 174 medical orders for off-label drug use, and the incidence was 33. 61%. The main factors of off-label drug use were off-label indications. The secondary factors were the administration routes. The general factors were off-label population, off-label usage and dosage, and off-label precautions. CONCLUSIONS: Analysis of off-label drug use in the outpatient department of the hospital by Pareto chart is helpful to identify the main and secondary factors of off-label drug use in the outpatient department of the hospital. In response to these factors, medical institutions should continue to strengthen the management of off-label drug use and improve the level of rational drug use in hospitals. [ABSTRACT FROM AUTHOR]

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Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of α1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63–0.85; p ≤ 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65–0.84; p ≤ 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03–0.94; p = 0.028) compared to matched controls not on any α1-AR antagonist at the time of admission. These findings suggest that use of α1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.

OBJECTIVE: To investigate the off-label use of antiepileptic drugs in outpatient children with epilepsy, and to explore its influencing factors, so as to provide reference for rational use of antiepileptic drugs in children. METHODS: The cases of children with epilepsy in pediatric outpatient department of Chinese PLA General Hospital from Jan.2019 to Nov.2020 were summarized, and whether there was off-label drug use in the prescription of antiepileptic drugs was judged according to the contents of drug instructions.The types of off-label drug use and the offlabel use of various antiepileptic drugs were analyzed statistically, and the influencing factors of off-label drug use were discussed by univariate analysis. RESULTS: A total of 193 children with epilepsy were enrolled, of which 166 children were treated with antiepileptic drugs, totally 249 case-times of antiepileptic drugs.The three main types of off-label drug use were off-label age administration (85 case-times, 34. 1%), over single drug/additive administration (49 casetimes, 19. 7%), and off-label attack types (41 case-times, 16. 5%). Among various antiepileptic drugs, Topiramate tablets (78. 4%, 40/51) and Leveethracetam tablets (58. 8%, 30/51) accounted for a higher proportion of drugs with off-label age administration. Levetiracetam tablets (9. 8%, 5/51) accounted for the highest proportion of over-dose administration, and Clonazepam tablets (13. 6%, 3/22) accounted for the highest proportion of over-frequency administration.Levetiracetam tablets (51. 0%, 26/51) took the lead of off-label attack types, and Levetiracetam tablets (62. 7%, 32/51) accounted for the highest proportion of over single drug/additive administration. CONCLUSIONS: Off-label use of antiepileptic drugs is common in pediatric outpatient department, especially off-label age administration, among which Levetiracetam tablets and Topiramate are the most prominent. Age and basic drugs affect the use of pediatric antiepileptic drugs in our hospital. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence and potential indications of PDE5 inhibitor use among pregnant and reproductive‐age women in the United States. Methods: We identified women 15 to 50 years with a livebirth from January 2001 through March 2018 in Sentinel Database. We assessed the prevalence of PDE5 inhibitor use prior to and during pregnancy by trimester, identified potential on‐ and off‐label indications using predefined diagnosis codes recorded within 90 days before the estimated last menstrual period through delivery. Separately, we used data from IQVIA's National Prescription Audit and Total Patient Tracker to estimate the dispensed prescriptions for PDE5 inhibitors and the number of patients with PDE5 inhibitor prescriptions. Results: We identified approximately 3.3 million pregnancies during 2001 to 2018, 96 of which had PDE5 inhibitor use during pregnancy. Prevalence of PDE5 inhibitor use was 2.61, 0.62, and 0.62 per 100, 000 live‐born pregnancies during the first, second, or third trimesters, respectively. Among women exposed to a PDE5 inhibitor from 90 days before conception to the end of pregnancy, 25.0%, 31.1%, and 15.5% had a diagnosis code for fetal growth restriction, preeclampsia, and pulmonary arterial hypertension. In IQVIA data, an estimated 223, 000 prescriptions from July 2015 through June 2018 and 58, 000 women received prescriptions for PDE5 inhibitors in 2017, of whom approximately 15, 000 (26%) were aged 15 to 50 years. Conclusion: We found a low prevalence of PDE5 inhibitor use in pregnant and reproductive‐age women. Given the very low prevalence of use and the inconsistency of neonatal mortality data across STRIDER centers, the risk to public health is low at present. [ABSTRACT FROM AUTHOR]

Neonates continue to be treated with off-label or unlicensed drugs while in hospital. However, some medications that have previously been used in adults underwent clinical testing and licensure for use with a different indication in the neonatal and pediatric population. Almost always, the marketing of these newly approved substances in a niche indication is accompanied by a steep increase in the price of the compound. We investigated the use of the approved formulation or the cheaper off-label alternative of Ibuprofen (Pedea®), Propanolol (Hemangiol®) and Caffeine Citrate (Peyona®) in neonatal clinical practice by conducting a National Survey of 214 Perinatal Centers in Germany. We also assessed price differences between on- and off-label alternatives and the extend of the clinical development program of the on-label medication in the neonatal population. On-label medication was more frequently used than the off-label alternative in all indications (PDA: on-label to off-label ratio 1:0.26, Apnea: 1:0.56, Hemangioma 1:0.76). All sponsors did conduct placebo-controlled Phase III trials with efficacy and safety endpoints in the target population and the number of participants in the target population varied between 82 and 497. Costs for the three drugs in their approved and marketed formulations increased in median 405-fold compared with the corresponding off-label alternative. Overall, about one out of three neonatologists prescribed an off-label or non-approved drug to patients despite an alternative medication that is approved for the indication in the target population being available.

Background. Children constitute a special population for off-label drug use (OLDU), yet limited drug-focused data exist regarding pediatric OLDU in clinical practice. This study aimed to investigate pediatric OLDU practice and compare it with pediatric drug utilization patterns of routine prescribing data. Methods. This cross-sectional study examined all approved pediatric OLDU applications, compared with electronic prescription data on national Prescription Information System of Turkish Medicines and Medical Devices Agency in 2015. OLDU applications and prescriptions were analyzed for demographic characteristics, healthcare/socioeconomic indices as well as details of drugs and diagnoses. Results. We found 7,896 OLDU applications and 7,029,512 prescriptions for the pediatric population in 2015. OLDU applications and prescriptions were mostly practiced for "2-11-year-old" children (52.7% vs. 63.4%, respectively; p<0.01). OLDU applications and prescriptions were detected to have a positive correlation with socio-economic development index (r = 0.45, p<0.0001 and r: 0.40, p = 0.0002; respectively) and the physician density (r = 0.66, p<0.0001 and r: 0.43, p<0.0001; respectively). In addition, OLDU was also positively correlated with the number of hospital beds per province (r = 0.39, p = 0.0003). Antineoplastic/immunomodulating agents were the most commonly applied drug category in OLDU (47.0%), compared with respiratory system drugs (36.6%) in routine prescribing. Eculizumab (6.5%), mycophenolate (5.6%), and canakinumab (4.4%) were the top drugs used as off-label. OLDU applications and routine prescription data revealed the most frequent diagnosis as "I27-other pulmonary heart diseases" (7.4%) and "J06-acute upper respiratory infections" (12.6%), respectively. Conclusions. This is the first nationwide study to show indication- and drug-centered aspects of pediatric OLDU and prescribing practice. Though OLDU applications is overall consistent with routine clinical practice in terms of demographics and institutional capacity, substantial variations exist regarding main drug classes and diseases. Our findings are expected to shed light on interventions focused on improving "indicated" pediatric use of drugs currently applied as off-label. [ABSTRACT FROM AUTHOR]

Purpose: To assess the frequency and possible predictors of off-label drug use in ambulatory pediatric units of four tertiary healthcare institutions in a Pakistani city. Methods: A prospective study was conducted at the pediatric ambulatory department of four tertiary care hospitals of Peshawar, Pakistan. A total 1589 patients were included in the study which to evaluate their prescriptions for off-label drug use with the aid of Thomson Healthcare Micromedex DRUGDEX database. Results: A total of 79 different drugs were prescribed 5668 times to pediatric patients. A high rate of offlabel drug use (71.8 %) was observed in this study. Compared to corresponding reference categories, infants (OR 4.134, 95 % CI 2.076-8.235) and children (OR 1.857, 95 % CI 0.967-3.568) were more likely to receive off-label prescriptions. However, pediatric patients receiving less than four drugs (OR 0.414, 95 % CI 0.312-0.548) were less likely to receive off-label prescriptions. Conclusion: A high incidence of off-label drug use has been observed in the ambulatory pediatric population studied, especially in infants. More research is needed to identify and evaluate the contributory factors to off-label use of drugs in ambulatory pediatric population in developing countries to achieve optimal drug therapy for pediatrics. [ABSTRACT FROM AUTHOR]

Objective: Off-label drug use (OLDU) of neurologic diseases is approved by a regulatory authority, the Turkish Medicines and Medical Devices Agency (TMMDA) in Turkey. It was aimed to investigate the most common neurologic drugs relevant to off-label prescribing and the most prescribed diagnosis, demographic and medical characteristics of patients with OLDU applications in Turkey. Materials and Methods: Four years "TMMDA"s electronic OLDU application records, 9,758 applications in total, were evaluated retrospectively. Information regarding patients' demographic characteristics, diagnoses, ordered drugs, and institutions were evaluated. Results: The most OLDU applications were mostly made in 2015, the majority of which were associated with neurodegenerative diseases. The mean age of the patients was 41.6 years and 65% were female. Some 62.1% of off-label drug application patients' age range was found as 18-64 years. The most common applications were from the Marmara region with 36% and neurology clinics of university hospitals with 81%. Multiple sclerosis (MS) was the most common diagnosis and the most frequently used group of drugs was disease-modifying drugs used in the treatment of MS. Conclusion: Based on the four-year survey of OLDU applications for adult neurologic patients showed that unlicensed drug prescriptions were high. There are very few studies on the result of OLDU applications in neurology worldwide. We believe that this study will be a guide to neurologists with off-label application processes and the results in our country and will make a significant contribution to the literature. [ABSTRACT FROM AUTHOR]

Purpose Analgesics are the most frequently administered medications among hospitalized children. However, current analgesic prescribing patterns have not been well defined among hospitalized children. In addition, it is unknown what proportion of prescription analgesics is approved for use in children and what proportion is used "off‐label." Methods: Nationally representative data from 52 tertiary care children's hospitals in the Pediatric Health Information System were queried to determine prescribing rates of analgesic medications. We analyzed hospitalizations for children <18 years occurring between 1 April 2010 and 30 June 2018. Food and Drug Administration (FDA) drug labels were reviewed for pediatric information, and prescriptions were classified as on‐ or off‐label based on age, route, and formulation. Results: Among 4.9 million hospitalizations, 1.8 million (37.6%, 95% confidence interval [CI] = 37.6‐37.7) were associated with use of a prescription analgesic. Overall, 36.7% (95% CI = 36.7‐36.7) of hospitalizations included off‐label analgesic therapy, with 26.4% (95% CI = 26.4‐26.5) associated with two or more off‐label analgesics. Off‐label analgesic use was higher among hospitalizations in the intensive care unit (61.5%) or with an operating room procedure (92.8%). Rates of off‐label prescribing increased with age, peaking at 50.5% for adolescents. Prescription analgesics administered most frequently were morphine, fentanyl, and ketorolac, with off‐label use occurring in 24.5%, 23.1%, and 11.3% of hospitalizations, respectively. Conclusions: Over a third of pediatric hospitalizations were associated with the administration of prescription analgesics that have not been labeled for use in children. Our findings highlight the critical need to ensure that safe and effective analgesics are developed for children and that pediatric labeling is expanded for existing analgesics to inform treatment decisions. [ABSTRACT FROM AUTHOR]

The Summary of Product Characteristics contains information on the optimal use of a medication, which allows for achieving the best therapeutic effect and guaranteed patient safety. That document defines the action of lege artis. A physician is not, in general, responsible for the adverse effects of a particular medication on the patient's health when following these guidelines. Deviations from them may be qualified as a so-called medical error and lead to multifaceted legal liability. However, the indications contained in the Summary of Product Characteristics are abstract and do not necessarily have to be case-specific. Sometimes proper therapeutic management even requires a derogation from these directives. Therefore, the article discusses the legal constructions that are applicable in this respect. From the perspective of criminal law, this issue should be considered through the prism of the so-called required precautionary rules. From the civil law perspective, so-called due diligence should be taken into account. Compliance with these rules excludes liability. The study approximates these constructions and discusses them, taking into account the medical law regulations that entitle a physician to choose the method of treatment. Apart from these requirements, the sine qua non of the legality of off-label therapy is to obtain legally valid consent from the patient. The article presents its premises in terms of the scope of the information obligation and other conditions of informed consent, which are important in the case of off-label prescription of the drug. [ABSTRACT FROM AUTHOR]