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Fertility preservation represents one important goal of cancer patients’ management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues. Supporting data demonstrate a significant advantage for the survivors who received GnRHa in the long-term maintenance of ovarian function and preservation of fertility. The prevention of the risk of ovarian failure with GnRHa is a typical off-label use, defined as the administration of a medicinal product not in accordance with the authorized product information. Italy has officially recognized the off-label use of GnRHa in adult women at risk of premature and permanent menopause following chemotherapy. However, fertility preservation still represents an unmet medical need in adolescents who cannot access to other treatment options.

Abstract Objectives: To identify drugs that were administered off label to hospitalized patients with suspected coronavirus disease 2019 (COVID-19) and to identify adverse drug reactions (ADRs) and drug–drug interactions associated with these therapies. Methods: This case–control study was conducted in a Brazilian hospital from March to April 2020 among patients with suspected COVID-19, comparing those with positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcriptase polymerase chain reaction (RT-PCR) results and those with negative results. Results: The most commonly used medications in both groups were azithromycin and hydroxychloroquine. There was a significantly higher prevalence of reactions among patients with positive RT-PCR for SARS-CoV-2 (48.5% vs 28.8%; P = .008) in the propensity score–matched cohort, and the most commonly reported ADRs among these patients were diarrhea (43.8%), elevated liver enzymes (31.3%), and nausea and vomiting (29.7%). Conclusions: Our data demonstrate that ADRs and drug–drug interactions are common with off-label treatments for COVID-19.

In recent years, off-label and unlicensed drug use has extensively developed in the paediatric population. For a long time, clinical trials in the paediatric population were considered complicated to perform because of ethical problems, causing frequent off-label use. Off-label drug use remains an important public health issue, especially for children with rare conditions or with diseases not responsive to conventional treatments. The present paper is a narrative review of the literature of off-label drug use in children. The aim of our study is to summarize the main works dealing with the off-label use of biological drugs in paediatrics. Further studies analyzing their efficacy, safety, and cost–benefit ratios are needed to extend the use of biological therapies to the paediatric population.

IgE plays an important role in the allergic diseases. More and more publications focus the attention ot IgE participation in non-allergic conditions. Therefore, there are already publications on the successful off-label use of anti-IgE therapy (omalizumab) in diseases such as mastocytosis, urticaria - vasculitis, systemic lupus erythematosus, bullous dermatoses and others. We present our clinical experience in the off-label application of omalizumab in 2 children: a 10-year-old boy with cystic fibrosis and aspergillosis and a 9-year-old girl with normocomplementary urticaria-vasculitis. [ABSTRACT FROM AUTHOR]

Fertility preservation represents one important goal of cancer patients' management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues. Supporting data demonstrate a significant advantage for the survivors who received GnRHa in the long-term maintenance of ovarian function and preservation of fertility. The prevention of the risk of ovarian failure with GnRHa is a typical off-label use, defined as the administration of a medicinal product not in accordance with the authorized product information. Italy has officially recognized the off-label use of GnRHa in adult women at risk of premature and permanent menopause following chemotherapy. However, fertility preservation still represents an unmet medical need in adolescents who cannot access to other treatment options. [ABSTRACT FROM AUTHOR]

Burn patients, especially children, experience many problems during their hospitalization. Because of their unique physiologic and altered pharmacokinetic profile, children receive more off-label prescribing than adults. The aim of this study was to analyze the incidence of off-label prescribing in burned children. This was a retrospective observational study conducted in the Dr. Soetomo General Hospital from December 2019 to March 2020. Data were collected from the medical records of burned children hospitalized over a 3-year period, from January 2017 to December 2019. Burn patients under 18 years old who received at least one prescribing medication were enrolled in this study. Twenty-six burned children met the inclusion criteria. A total of 215 medications were prescribed during this study and 35% of them were classified as off-label. The term off-label for age range was the highest among the off-label prescribing medicines, as much as 53%, with 30% classified for an unapproved indication, 15% for an unapproved dosage, and 2% for an unapproved dosage form. The prevalence of off-label prescribing was higher in children from 2 to 12 years old than in adolescents. Analgesics were the therapeutic classes most often prescribed as off-label in burned children. Most burned children are administered off-label medication with uncertain evidence. Further research is needed in this population to focus on several medications with high risk potential. [ABSTRACT FROM AUTHOR]

A pediatric population is a specific group of patients. Due to the considerable physiological changes, extensive knowledge of the pharmacological and pharmacokinetic properties of medications is required to adjust pharmacotherapies to children properly. The objective of this paper is to evaluate the prescribing patterns of pediatric medications and the frequency of administering off-label medications for children, as well as to identify quantitative and qualitative errors in prescriptions for children. A retrospective (consecutive) analysis of prescriptions for pediatric patients in community pharmacies in Poland was undertaken. Prescriptions for children were most often issued by pediatricians (66.09%) in the city, and by specialists in family medicine (78.46%) in the town. The percentage of prescribing errors, in the form of a lack of dose specification, was relatively high (17.51% in the city and 32.84% in the town). Most of the medications prescribed for children comprised respiratory system drugs (R) and antiinfectives (J) (ATC classification). It has been shown that quite a large number of pediatric prescriptions contained errors. The role of pharmacists in evaluating the selection of medications for this group of patients should be emphasized [ABSTRACT FROM AUTHOR]

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary. [ABSTRACT FROM AUTHOR]

Importance: While dupilumab has emerged as an effective treatment for moderate-to-severe atopic dermatitis (AD) since its approval in 2017, interleukin-4 and 13 blockade has also demonstrated efficacy in off-label chronic dermatologic conditions. Objective: To identify chronic dermatologic conditions in which dupilumab has demonstrated efficacy. Findings: Thirty-three reports of dupilumab use in non-AD dermatologic conditions were identified through systematic literature review. Effective use of dupilumab has been reported in case reports and case series in the treatment of chronic pruritus, prurigo nodularis, eczematous eruption of aging, allergic contact dermatitis, chronic hand eczema, alopecia areata, urticaria, eosinophilic annular erythema, bullous pemphigoid and papuloerythroderma of Ofuji. Clinical trials are underway evaluating the efficacy of dupilumab in allergic contact dermatitis, chronic hand eczema, alopecia areata, chronic spontaneous urticaria and cholinergic urticaria. Conclusions and relevance: Overlap in immune signaling pathways between AD and chronic pruritus, eczematous eruption of aging, allergic contact dermatitis, chronic hand eczema, alopecia areata, urticaria, eosinophilic annular erythema, bullous pemphigoid and papuloerythroderma of Ofuji make these conditions candidates for dupilumab therapy when standard treatments have failed or are contraindicated. While promising as a therapeutic option, off-label prescribing of dupilumab requires consideration of challenges in insurance authorization and out-of-pocket cost to the patient. [ABSTRACT FROM AUTHOR]

To retrospectively analyze the off‐label prescriptions at a plastic surgery hospital in China and conduct a literature review. The prescriptions in outpatient department from January 1, 2018 to December 31, 2018 were collected and compared with the related drug instructions in indications, dosage, frequency and route of administration to identify the off‐label prescriptions. According to related literatures, guidelines, and MICROMEDEX, the rationality of off‐label drug uses was evaluated. A total of 39 836 prescriptions were screened and 3395 (8.52%) off‐label prescriptions were identified. It involved 23 items off‐label medication uses. 20 items were off‐label used in indication and three items were in indication and administration route. These off‐label prescriptions involved 19 medicines and 12 indications and the dermatology related drug usage accounted for the largest proportion (91.3%). Additionally, five items (21.7%) were Chinese patent medicine related. Of the 23 items, seven (30.4%) have been recommended by guidelines and two (8.7%) by Thomson Grading System of Micromedex. All of them have been proved by literature evidence of level 1 to 4, in which 19 (82.6%) by Level 1 evidence, 21 (91.3%) by Level 1 to 2 evidence and 2 (8.7%) only by level 3 to 4 evidence. This can provide a theoretical basis to clinicians in prescribing. Our next work is to perfect some details about evidence assessment to improve the reliability. [ABSTRACT FROM AUTHOR]

Purpose: Conventional ultrasound is the main imaging modality in obstetrics for assessing the maternal and fetal status. Up to date, contrast-enhanced ultrasound (CEUS) has not found widespread use in gynecology and obstetrics, but recent studies demonstrate promising results. The aim of the present study is to assess safe and valuable application of CEUS during pregnancy to investigate non-obstetric conditions. Methods: Five pregnant patients on whom CEUS was performed between 2019 and 2020 were included in this retrospective single-center study. A total of six CEUS examinations were performed including one CEUS-guided biopsy (mean age: 31 years, mean weeks of pregnancy: 18 weeks). CEUS examinations were performed by a consultant radiologist (EFSUMB level 3). Results: All included pregnant women safely underwent CEUS. Neither maternal nor fetal adverse effects were detected. CEUS critically helped in the diagnostic workup of a desmoid tumor of the abdominal wall, hepatic hemangioma, amebic hepatic abscess, uncomplicated renal cyst and post-inflammatory alteration of the renal cortex and for excluding active abdominal bleeding. In addition, CEUS-guided biopsy was performed to prevent intratumoral hemorrhage. Findings from CEUS prompted immediate treatment in two women, whereas in three women regular obstetric monitoring of the women could be conducted. Conclusion: Our results demonstrate safe and crucial application of off-label CEUS in pregnant women to assess different non-obstetric conditions allowing to prevent additional ionizing CT or application of (gadolinium-based) contrast agent in MRI. Hence, CEUS might add pivotal value for evaluating obstetric and non-obstetric conditions and thereby directing clinical management of pregnant women in the future. [ABSTRACT FROM AUTHOR]

Background/Objectives: Atopic dermatitis (AD) affects up to 20% of the pediatric population, with a growing prevalence over the past 30 years. Topical corticosteroids (TCS) are commonly used as a first‐line topical therapy for AD and are prescribed in 59% of all AD visits. However, some topical corticosteroids are prescribed outside of their age range indications. This paper aims to explore the frequency with which topical corticosteroids are prescribed for AD outside of their FDA‐approved age range. Methods: Data on prescribing patterns for AD were obtained from the National Ambulatory Medical Care Survey (NAMCS). We assessed the frequency of off‐label use of topical corticosteroids with respect to age indications in four specific age‐groups, as delineated in the data (0‐1, 2‐7, 8‐18, and 19+ years). Results: All prescribed topical corticosteroids found in the NAMCS database have an indication for AD or other inflammatory dermatoses or pruritic dermatoses. However, some medications were prescribed outside of their FDA‐approved age indications. These off‐label prescription rates ranged from 52% for desoximetasone to 0% for halobetasol and alclometasone, or rates lower than could be detected by our study. Conclusions: Much like other medications for AD treatment, TCS are sometimes used off‐label. The off‐label use of topical corticosteroids to treat pediatric AD highlights a gap between clinical practice and regulating guidelines. Additional pediatric studies would offer a greater body of evidence to maintain or expand label indications for the use of TCS in younger patients. [ABSTRACT FROM AUTHOR]

Drug repurposing is a strategy that aims to develop novel cancer treatments through the reuse of existing medicines developed in other disease areas. Such a strategy includes the identification of candidate drugs, clinical development, drug licensing, reimbursement and clinical implementation. This review outlines a literature-based approach to candidate selection with illustrative examples in osteosarcoma, pancreatic cancer and perioperative therapies. Key issues related to the development of clinical trials, drug licensing/approval and clinical adoption are explored to highlight some of the obstacles that must be overcome to successfully repurpose a drug as a new therapeutic option. [ABSTRACT FROM AUTHOR]

The off-label use of medicines is neither prohibited nor explicitly allowed, according to the current European Union (EU) pharmaceutical legislation. This can cause confusion in physicians' practice as well as lead to patients' dissatisfaction. The purpose of this survey is to assess the knowledge and experience of Bulgarian physicians with the off-label use of medicines. The survey was performed at the beginning of 2020 in the biggest private hospital in South-Central Bulgaria. Ninety-six physicians from the inpatient and outpatient medical care participated in the survey and answered 10 questions. The data analysis was performed using the statistical program SPSS v19.0. The results are described as numbers and percentages for the qualitative variables and mean value (median due to their distribution) and a variance measure (range) for the quantitative ones. The distribution of the variables was tested with the Kolmogorov–Smirnov test. The evaluation of the relationships between the qualitative variables was performed using the χ2 test or the Fisher's exact test, where applicable. The results showed that most of the participants (81%) have never prescribed medicines off-label and believe it is not allowed to use medicines off-label (73%). Physicians strongly support the introduction of clear rules for the off-label use (88%). In conclusion, physicians practicing outside of the capital city demonstrated good level of knowledge, but relatively low awareness and little experience with the off-label use of medicines. They feel also, uncertainty in their prescribing activities when they use medicines off-label and strongly support introduction of clear rules for the off-label use. [ABSTRACT FROM AUTHOR]

Aims: Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. Methods: Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997–2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. Results: Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. Conclusions: Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk–benefit ratio are needed. [ABSTRACT FROM AUTHOR]

Background: An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia., Methods: A cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05., Results: Among the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%)., Conclusion: There are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neda Shamie Maloney-Shamie Vision Institute, Los Angeles, CA, USACorrespondence: Neda ShamieMaloney-Shamie Vision Institute, 10921 Wilshire Blvd #900, Los Angeles, CA, 90024, USATel +1 301-882-6365Email ns@maloneyshamie.com View the original paper by Dr Motwani and colleagues

L Jay Katz1–3 1Glaucoma Research Center, Wills Eye Hospital, Philadelphia, PA, USA; 2Department of Ophthalmology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA; 3Glaukos, San Clemente, CA, USACorrespondence: L Jay KatzGlaukos, 229 Avenida Fabricante, San Clemente, CA, 92672, USATel +1 949-481-0459Email ljkatz@willseye.org View the original paper by Dr Motwani and colleagues

In the 1980s, recombinant human erythropoietin (rhEPO) began to be used in clinical practice. In this study, the clinical application of rhEPO from single-center in recent ten years was reviewed, and the scope of indications and clinical efficacy were evaluated. The medical records of 35829 in-patients who were treated with rhEPO in the first Medical Center of the Chinese PLA General Hospital from 2009 to 2018 were collected. According to the scope of indications approved by CFDA (China Food and Drug Administration), curative effect and off-label of rhEPO were analyzed. Of the 35829 patients, 19013 (53.1%) were male and 16816 (46.9%) were female, with an average age of (52.1 ± 18.6) years. The usage of rhEPO is increasing year by year. The overall effective rate was 53.1%. The number of patients who met the indications accounted for 67.2%, and the effective rate patients with indications and Off-label were 48.8% and 50.7%. Among the patients with irregular use of rhEPO perioperative imperfect laboratory examination patients accounted for the highest proportion (7.1%). The volume of RBC(s) (red blood cell(s)) transfusion in patients with rhEPO was significantly less than that in patients without rhEPO (p

Abstract This study used retrospective chart review and survey data to evaluate: (1) off‐label use of rituximab (MabThera®/Rituxan®) in autoimmune conditions and (2) patients’ receipt and knowledge of the Patient Alert Card (PAC), a risk minimization measure for progressive multifocal leukoencephalopathy (PML) and serious infections. Anonymized patient data were collected from infusion centers in Europe from December 2015 to July 2017. Adults receiving rituximab in the same centers were provided a self‐administered survey. Outcomes included patterns of off‐label rituximab use for nononcology indications, and evaluation of patients’ receipt and knowledge of the PAC and its impact. Of 1012 patients in the retrospective chart review, 70.2% received rituximab for rheumatoid arthritis or granulomatosis with polyangiitis/microscopic polyangiitis, and 29.8% received rituximab off label. Among 524 survey participants, 32.8% reported receiving the PAC, 59.3% reported not receiving the PAC and 7.9% did not know whether they received the PAC. A total of 72.4% of patients reported that they were unaware that some patients receiving rituximab experience PML. A higher proportion of PAC recipients identified PML as a potential risk of rituximab than nonrecipients (37.8% vs 19.9%); 58.3% of PAC recipients had poor awareness of PML. Most PAC recipients (90.0%) and nonrecipients (85.5%) correctly answered that they should seek medical attention for infection symptoms. In conclusion, approximately 30% of patients received off‐label rituximab. Most patients reported not receiving the PAC or having knowledge of PML but demonstrated understanding of the recommended action in the event of infection symptoms, regardless of PAC receipt.

Background: Tanreqing injection (TRQ) is a traditional Chinese medicine commonly used in China to treat pulmonary diseases presenting as phlegm-heat syndrome. Robust data on the safety of TRQ from real-world observational cohorts are currently lacking.Objective: To evaluate as the incidence, type, and predictors of adverse events (AEs) and adverse drug reactions (ADRs) of TRQ in clinical practice in China.Methods: We conducted a population-based cohort, multicenter study to evaluate the incidence, manifestation, outcomes, and risk factors of AEs and ADRs following TRQ use in China. Between April 2014 and May 2015 a total of 30,322 consecutive inpatients/emergency attendance patients from 90 hospitals across China administrated TRQ were followed-up for 7 days. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression to identify predictors of ADRs.Results: The incidence of AEs and ADRs was 1.4 and 0.3%, respectively. Skin and subcutaneous tissue disorders were the most common ADRs. All ADRs were mild or moderate in severity, except for one serious case of anaphylactic reaction. The majority of ADRs (72.8%) occurred in the first 2 h after TRQ administration. Two-thirds of patients (66.1%) in the study were prescribed TRQ off-label, including infants aged ≤24 months. A history of food allergy (OR 4.50, 95% CI: 1.35–15.00), drug allergy (OR 2.77, 95% CI: 1.56–4.94), and fast infusion speed (off-label use) (OR 2.10, 95% CI: 1.27–3.50) were associated with an increased risk of ADRs.Conclusion: TRQ is well tolerated in the general population, yet off-label use is prevalent. Efforts are required to educate prescribers to adhere to the drug label in order to minimize potential patient harm.

Background: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. Case Report: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient’s renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. Conclusions: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (

Non-steroidal anti-inflammatory drugs (NSAIDs) are liders in selling both in the Russian Federation and worldwide. The combination of analgesic, anti-inflammatory and antipyretic effects make the drugs of this group very popular in patients with various diseases. The realization of NSAIDs in pharmacies occurs both by prescription and over-the-counter, so the safety assessment of the use of this group of drugs remains relevant. In the current practice, self-administration (responsible selfmedication) of drugs of the NSAID group is an additional factor affecting the safety of their intake. According to the studies, about 40 % of patients taking NSAIDs consider that NSAIDS are absolutely safe, and more than 30 % of those taking OTC NSAIDs use them in excess of the recommended dosages. We analyzed 3963 individual case safety reports (ICSR) in the federal database «Pharmacovigilance» from 07.12.2008 to 31.08.2017. The inclusion criterions was the presence of information on the off-label application of NSAIDs in the ICSR, reports of adverse effects that may be associated with the use of this drug or erroneous reports on the active substance, which was not present in this drug. The most frequent mistakes in the application were an increase of the daily dose, a change in the method of administration to patient who are contraindicated with this drug. There were 9 ICSR of burning sensation in the anus with the introduction of ibuprofen suppositories (not in the label), and 7 ICSR of ineffectiveness of the active substance, which was not present in this drug.

LLC Novartis Pharma, Moscow, Russian Federation Abstract. The problem of off-label use is still unsolved during the pharmacotherapy in children. In connection with the above, the need to stimulate the conduct of specially organized clinical studies, the purpose of which will be to evaluate the efficacy and safety of using drugs in children in different age groups, becomes evident. However the complexity of the organization of clinical studies in pediatrics is associated not only with regulatory aspects but also with lack of understanding of the importance of these studies by pediatricians and parents. The authors conducted a study aimed at finding out the frequency of off-label prescriptions in the Russian Federation in pediatric practice and doctors’ and parents’ attitude to this kind of use of medications. The study has shown the evidence that the off-label prescription practice is widely-used in healthcare in Russia and is routine for most respondents. The highest frequency of off-label prescriptions is observed in the group of children from 0 to 5 years. The majority of physicians and parents don’t consider themselves responsible for popularization of clinical trials which indicates that this problem should be widely discussed in the society. Parents trust physicians in terms of therapy choices or their recommendations regarding participation in clinical trials. A portrait of a typical “staunch opponent” of clinical trials among parents.

The aim of this study was to evaluate the structure of etiotropic therapy used in the treatment of urinary tract infection in newborns, the frequency of using off-label etiotropic medicines, and assess the incidence of adverse drugs reactions (ADR). The work was carried out by a retrospective pharmacoepidemiology analysis of children hospitalized patient history (form 003/y) with infectious diseases in the period of the newborn. The object of the study is a case history of a stationary patient, the main method of research is the collection and analysis of information, the statistical processing of the data obtained. During the analysis, all the selected medical records were divided into two groups: the first - children, with the course of urinary tract infection, the second - with the course of infectious diseases of other localization. During the study it was demonstrated that the use of etiotropic therapy in children with urinary infection is higher than in children with the course of the infectious process of other localization. The frequency of off-label prescriptions for the treatment of urinary tract infection is 51%, and the incidence of ADR in the case of unadapted appointments is 1,4 times higher.

Purpose. To study the structure of serious adverse drug reactions and «off label» drug use in children by means of analysis of the national pharmacovigilance database. Materials and methods. We analyzed 341 spontaneous reports about serious adverse reactions in children, submitted to the Russian pharmacovigilance database in 2012, and 467 suchlike spontaneous reports registered in 2015. Results. Children of preschool age have higher risk of medical therapy complications. Most frequently, skin (33,4% in 2012 and 38,7% in 2015) and organism as a whole (21,4 and 21,1%, respectively) were involved in the pathological process. Antimicrobial drugs for systemic use (43,5% in 2012 and 43,8% in 2015) and drugs for nervous system (25,1 and 26,1% respectively) often caused them. Unexpected serious adverse reactions accounted for 16,9% of all complications in children in 2012, 10,8% in 2015. It was established that 58,7% of suspected medicines in 2012 and 47,5% in 2015, the use of which was associated with the development of serious complications in pharmacotherapy in children, were prescribed with deviations from the recommendations of approved prescribing drug information. The main types of «off-label» drug use were inappropriate indications, deviations from the recommended dosage regimen, the use of a drug in the age group of patients, wherein the drug has not been approved, and the use of a drug in the presence of contraindications to its use. Conclusion. Our research confirms that the practice of «off-label» drug use in children is an independent risk factor for developing adverse drug reactions. It is shown that the method of spontaneous reporting can help to identify the problems of drug safety and to develop recommendations for minimizing the risk of complications of pharmacotherapy in pediatric practice.

Objective: We analyzed prescribing patterns of antipsychotics for children and adolescent affiliated with a Danish Child and Adolescent Mental Health Center) with respect to age, sex, medicine, diagnoses, off-label status, and time. Methods: We included all patients below 19 years of age prescribed antipsychotics during 2007–2008 and as of November 1, 2014. Prescription data included all antipsychotic prescriptions and prescriptions of concomitant psychotropic medications. We defined an antipsychotic user as a patient receiving at least one prescription during the study period, irrespective of any previous history of antipsychotic use. We defined off-label prescribing as prescriptions outside the licensed age group and approved indication. Findings: We analyzed 404 antipsychotic prescriptions that were located for 150 patients. The patients were between 7 and 18 years of age. Two-thirds of the prescriptions were for girls and two-thirds of prescriptions for olanzapine and quetiapine. Totally, 92% of all prescribed antipsychotics were used off-label. For typical antipsychotics, this share was 96% and for atypical antipsychotics 90%. As of November 1, 2014, the total share of off-label antipsychotic prescriptions was 96%, and 63% of these were for medications prescribed outside the approved age group, and 26% for nonlicensed indication(s). Conclusion: This study demonstrated a high level of off-label prescribing over time with respect to age and indication. The prescribing patterns underpin the need for further economic incentives for pharmaceutical companies to register pediatric indications, particular for off-patent products.

Anti-vascular endothelial growth factor eye injections have become the most accepted and effective treatment for some of the leading causes of blindness. Aflibercept (Eylea; Bayer) is the most expensive item on the Pharmaceutical Benefits Scheme, (PBS) with ranibizumab (Lucentis; Roche/Novartis) ranked eighth. In 2011 the pharmaceutical cost for these treatments was A$237 million – now the figure is A$665 million and climbing. Bevacizumab (Avastin; Roche) is part of the original molecular lineage for a group of biologic agents, which were originally designed for cancer therapy. It is now administered worldwide on an off-label basis and in very large numbers for retinal vascular disease. It has a proven efficacy and safety profile. Bevacizumab is thirty times cheaper than the Therapeutic Goods Administration (TGA)-approved alternatives and its use could reduce PBS costs by hundreds of millions of dollars. Should the TGA be the sole arbiter in the approval of drugs, or should alternative bodies have some say in the approval of off-label usage under such compelling circumstances? Legislation for this approach has been approved in France, the UK, and Italy. Only by eliminating the legal risk to authorising bodies and physicians, and the financial disincentive to the patient associated with off-label use, will drugs such as bevacizumab be more widely adopted. What is known about the topic? Bevacizumab is known to be a far cheaper off-label alternative for the treatment of retinal vascular diseases such as age related macular disease, diabetic maculopathy and venous occlusive disease. Cost, litigation pressures and supply issues continue to limit its use in Australia. What does this paper add? This paper discusses the approaches taken by other health jurisdictions and authorities around the world, enabling easier access to this drug and thus making massive cost savings to their respective health budgets. What are the implications for practitioners? Potentially enormous cost savings could be achieved by enabling easier access to bevacizumab. [ABSTRACT FROM AUTHOR]

COVID19, off-label, drug repurposing, emergency law, Italian regulatory system. [Extracted from the article]

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. Two databases (PubMed and ClinicalTrial.gov) were reviewed. Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is frequently prescribed off‐label in the community but little is known about the initiation and use of quetiapine in general (non‐psychiatry) hospital settings. Aim: This study examined the extent of off‐label quetiapine prescribing and rates of initiation of quetiapine in a general inpatient population of an Australian inner city teaching hospital, as well as the frequency of communication with community prescribers following discharge. Methods: A retrospective observational study was conducted of all patients admitted under all non‐psychiatric teams and prescribed quetiapine within a tertiary teaching hospital between 1 January 2011 and 31 December 2016. All quetiapine prescribing information was extracted from an electronic medication management system (EMMS) and medical records were reviewed for a random sample of 100 patients prescribed quetiapine. Results: EMMS data indicated that 793 people were prescribed quetiapine over the study period. Quetiapine was most frequently prescribed once daily, with a median daily dose of 100 mg (interquartile range 37.5–200 mg). Eighty‐seven of the 100 medical records reviewed had corresponding discharge summaries, and potentially off‐label quetiapine prescribing was found in 48 people (55%); the most frequent off‐label indication was for agitation or delirium. Of the 33 people who had quetiapine initiated in hospital, 26 prescriptions (79%) were for off‐label indications. Of the 11 prescriptions (33%) continued at discharge, only three (27%) discharge summaries contained instructions to community prescribers regarding quetiapine. Conclusion: Off‐label prescribing of quetiapine was common in this sample of inpatients, and senior hospital staff should remain cautious of quetiapine prescribing for indications where the evidence of harms and benefits remains unclear. Communication with community prescribers could also be improved to reduce the risk of conversion from intended short‐term off‐label use to longer‐term use. [ABSTRACT FROM AUTHOR]

In the 1980s, recombinant human erythropoietin (rhEPO) began to be used in clinical practice. In this study, the clinical application of rhEPO from single-center in recent ten years was reviewed, and the scope of indications and clinical efficacy were evaluated. The medical records of 35829 in-patients who were treated with rhEPO in the first Medical Center of the Chinese PLA General Hospital from 2009 to 2018 were collected. According to the scope of indications approved by CFDA (China Food and Drug Administration), curative effect and off-label of rhEPO were analyzed. Of the 35829 patients, 19013 (53.1%) were male and 16816 (46.9%) were female, with an average age of (52.1 ± 18.6) years. The usage of rhEPO is increasing year by year. The overall effective rate was 53.1%. The number of patients who met the indications accounted for 67.2%, and the effective rate patients with indications and Off-label were 48.8% and 50.7%. Among the patients with irregular use of rhEPO perioperative imperfect laboratory examination patients accounted for the highest proportion (7.1%). The volume of RBC(s) (red blood cell(s)) transfusion in patients with rhEPO was significantly less than that in patients without rhEPO (p<0.05). The use of rhEPO Off-label is very common and has a certain curative effect. It can be used as evidence support for the update of the scope of indications. In addition, There are still irregular use of rhEPO and transfusion in clinic. The unreasonable use of rhEPO and transfusion should be further standardized to ensure the safety and effectiveness. [ABSTRACT FROM AUTHOR]

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The Roche/Novartis case raised an issue of European competition law so complex that it called upon the intervention of the most important and authoritative judicial body of the European Union, i.e. the Grand Chamber of the Court of Justice. Some of the outcomes of this case are, however, particularly worth analysing because they show to the highest degree the potential logical shortcomings that can be created by combining a too rigid and sterile application of competition law principles with complex factual circumstances. More specifically, in this case the legal questions of the definition of the relevant product market, of the competitive relationship between the parties and of the implications of a licensing agreement between them needed to be adjudicated with reference to the unlawfulness of the creation and marketing of the relevant product, of the marketing of such product by third-parties (and not by one of the infringers) and of the weight of regulatory issues within the competition law assessment. Despite the arguably unique set of facts of the case, the problematic - even contradictory - nature of its findings cautions us against a formalistic application of competition law and shows instead the preference of adopting a substantive approach within the competition law assessment. [ABSTRACT FROM AUTHOR]

Background: Furosemide is approved in full term neonates to treat edema associated with congestive heart failure, cirrhosis and renal diseases. It is often administered off-label in premature neonates, to treat respiratory conditions and at doses greater-than-recommended. We conducted a national survey on behalf of the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology (SIN), to investigate its use in Italian neonatal intensive care units (NICUs), in conformity with current guidelines. Methods: Between December 2016 and June 2017, a 14-item multiple-choice online questionnaire was sent to all NICU directors from the SIN directory. Gestational age, route of administration, posology, indications, referenced guidelines, adverse effects monitoring and the presence of Paediatric Cardiology or Cardiosurgery service on site were assessed. A chi-square test was performed 1) to evaluate differences in the distribution of responses between NICUs administering furosemide at doses higher-than-recommended; 2) to compare the proportion of NICUs administering furosemide at high doses in institutions with versus without a Paediatric Cardiology or Cardiosurgery service. Results: The response rate was 50% (57/114). The intravenous and oral routes were chosen primarily; the intravenous administration in single doses predominated over continuous infusion. Its main therapeutic indications were congestive heart failure/overload (94.7%) and oligo-anuria (87.7%) however furosemide was also frequently used for broncopulmonary dysplasia (50.9%) and respiratory distress syndrome and/or transient tachypnea of the newborn (24.6%). In 28/57 NICUs furosemide was administered at doses higher-than-recommended. In most NICUs the same posology was used in term and preterm neonates. Compared to the total sample, a larger proportion of NICUs administering doses greater-than-recommended referenced current literature for reasons to do so (19.3 and 32.1% respectively). The presence of a Paediatric Cardiology or Cardiosurgery service on site did not correlate with the chosen posology. The majority of NICUs performed acoustic test and renal ultrasound for furosemide exposure greater than 2 weeks. Conclusions: In Italian NICUs, furosemide is commonly prescribed to term and preterm newborns for label and unlabeled indications. Doses greater-than-recommended are frequently administered. Such use is not necessarily inappropriate. More research is required to assess the efficacy and safety of unlabeled use. [ABSTRACT FROM AUTHOR]

Purpose: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication. Materials and methods: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term 'apremilast,' with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available. Results: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet's disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis. Conclusion: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role. [ABSTRACT FROM AUTHOR]

Purpose: To analyse current off-label use of bevacizumab for wet age-related macular degeneration (AMD) in Europe. Methods: The study was conducted as a combined survey and literature review. It included the 22 most populous countries in Europe. In each country, ophthalmologists with particular knowledge about off-label treatment responded to a questionnaire. Results: Answers were obtained from twenty European countries. The off-label use of bevacizumab for wet AMD greatly differed between nations; the bevacizumab proportion varied from non-existent (0%) to very high (97%). There were also large disparities within single countries (e.g. 0–80%), which were attributable to differences in regional decision-making. Both governmental institutions and national ophthalmological societies expressed highly diverging opinions on the use of off-label treatment. Intravitreal administration of bevacizumab had been a matter of legal dispute in several countries. The question about responsibility for off-label therapy mainly remained unanswered. Conclusions: There was a highly varying utilization of bevacizumab between European countries. Despite an intention of a consistent approach to medical regulations, Europe has not yet reached a professional or political consensus on the ophthalmic off-label use of bevacizumab. [ABSTRACT FROM AUTHOR]

We present our initial experience with the off-label use of the Woven EndoBridge (WEB) device. We performed a retrospective study from 2 institutions of patients with intracranial aneurysms who underwent treatment with the WEB device alone or in conjunction with stenting and/or coiling in an off-labeled location. Eleven patients with 12 aneurysms were included. Four (30.8%) aneurysms presented ruptured. Off-labeled locations included 3 aneurysms in the posterior communicating artery, 3 in the supraclinoid ophthalmic artery, 2 in the pericallosal artery, 2 in the posterior inferior cerebellar artery, 1 at the vertebrobasilar junction, and 1 in the cavernous internal carotid artery. Mean dome-to-neck ratio was 1.91 ± 0.9. Average duration of the procedure was 63.9 ± 29.6 minutes. Femoral route was used in 61.5%, and radial access in 48.5% of cases. Five procedures (41.7%) were performed under monitored anesthesia care. We had 1.33 attempts per aneurysm. WEB embolization was supplemented with coiling in 2 cases (16.67%) and stenting in 1 case (8.3%). Based on the O'Kelly-Marotta ("OKM") grading scale, we report a rate of 0% for grade 1, 33.3% for grade 2, and 33.3% for grade 3. Postprocedural occlusion was complete in 4 (33.3%) and adequate in 8 (66.6%) patients. No procedure-related deaths or symptomatic complications were reported. The WEB device was successfully deployed in off-labeled locations, including posterior communicating artery, ophthalmic artery, and pericallosal aneurysms. The efficacy of this usage must be evaluated in multicenter prospective studies, but our preliminary results are promising. Correct characterization of the aneurysm size/morphology, as well as awareness of possible adjunct treatments, are crucial for successful intervention. [ABSTRACT FROM AUTHOR]

This study used retrospective chart review and survey data to evaluate: (1) off-label use of rituximab (MabThera®/Rituxan®) in autoimmune conditions and (2) patients' receipt and knowledge of the Patient Alert Card (PAC), a risk minimization measure for progressive multifocal leukoencephalopathy (PML) and serious infections. Anonymized patient data were collected from infusion centers in Europe from December 2015 to July 2017. Adults receiving rituximab in the same centers were provided a selfadministered survey. Outcomes included patterns of off-label rituximab use for nononcology indications, and evaluation of patients' receipt and knowledge of the PAC and its impact. Of 1012 patients in the retrospective chart review, 70.2% received rituximab for rheumatoid arthritis or granulomatosis with polyangiitis/microscopic polyangiitis, and 29.8% received rituximab off label. Among 524 survey participants, 32.8% reported receiving the PAC, 59.3% reported not receiving the PAC and 7.9% did not know whether they received the PAC. A total of 72.4% of patients reported that they were unaware that some patients receiving rituximab experience PML. A higher proportion of PAC recipients identified PML as a potential risk of rituximab than nonrecipients (37.8% vs 19.9%); 58.3% of PAC recipients had poor awareness of PML. Most PAC recipients (90.0%) and nonrecipients (85.5%) correctly answered that they should seek medical attention for infection symptoms. In conclusion, approximately 30% of patients received off-label rituximab. Most patients reported not receiving the PAC or having knowledge of PML but demonstrated understanding of the recommended action in the event of infection symptoms, regardless of PAC receipt. [ABSTRACT FROM AUTHOR]

Neonatal anaesthesia dosing needs to be based on physiological characteristics of the newborn, pharmacokinetic knowledge, pharmacodynamic considerations and the adverse effects profile. Disease processes and treatments in this group are distinct from adults. Immaturity of enzyme, anatomical and physiological systems cause extensive variability of drug disposition and drug response in neonates. This is further compounded by pharmacogenomic influences. Postmenstrual age is a reasonable measure for maturation of clearance pathways. The neonatal response to drugs is altered and monitoring of effect that guides adult drug use is limited. While neuromuscular monitoring is robust, few other clinically applicable tools are available to provide pharmacodynamic effect feedback. Tools that assess depth of anaesthesia, sedation and pain in neonates have potential to improve effectiveness and safety. [ABSTRACT FROM AUTHOR]

The skin is one of the largest organs in the human body. Majority of skin diseases requires lifelong treatments since they are chronic in nature. Thereby, appropriate diagnosis by the physicians and rational prescription of drugs becomes a vital component of drug therapy. ADR monitoring is considered to be mandatory as they become severe and potentially life-threatening. Primarily, in off-label setting, patients are treated with drugs which are not registered for that specific indication. Dermatologists have been at the forefront of the application of azathioprine and have thus been using the immunosuppressant for treating patients over several years. [ABSTRACT FROM AUTHOR]

Background: Tanreqing injection (TRQ) is a traditional Chinese medicine commonly used in China to treat pulmonary diseases presenting as phlegm-heat syndrome. Robust data on the safety of TRQ from real-world observational cohorts are currently lacking. Objective: To evaluate as the incidence, type, and predictors of adverse events (AEs) and adverse drug reactions (ADRs) of TRQ in clinical practice in China. Methods: We conducted a population-based cohort, multicenter study to evaluate the incidence, manifestation, outcomes, and risk factors of AEs and ADRs following TRQ use in China. Between April 2014 and May 2015 a total of 30,322 consecutive inpatients/emergency attendance patients from 90 hospitals across China administrated TRQ were followed-up for 7 days. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression to identify predictors of ADRs. Results: The incidence of AEs and ADRs was 1.4 and 0.3%, respectively. Skin and subcutaneous tissue disorders were the most common ADRs. All ADRs were mild or moderate in severity, except for one serious case of anaphylactic reaction. The majority of ADRs (72.8%) occurred in the first 2 h after TRQ administration. Two-thirds of patients (66.1%) in the study were prescribed TRQ off-label, including infants aged ≤24 months. A history of food allergy (OR 4.50, 95% CI: 1.35–15.00), drug allergy (OR 2.77, 95% CI: 1.56–4.94), and fast infusion speed (off-label use) (OR 2.10, 95% CI: 1.27–3.50) were associated with an increased risk of ADRs. Conclusion: TRQ is well tolerated in the general population, yet off-label use is prevalent. Efforts are required to educate prescribers to adhere to the drug label in order to minimize potential patient harm. [ABSTRACT FROM AUTHOR]

Background: Off-label drug use refers to any use of an approved or cleared drug that is not included in that product's approved labeling or cleared indications for use. It may be in terms of indication, age group, dosage, or route of administration. Off-label drug prescriptions are common neurology practice. Aim: The aim of the study is to evaluate the prevalence pattern of off-label drug use in neurology. Subjects and Methods: A prospective, observational, cross-sectional study was carried out in the neurology outpatient department of tertiary care teaching hospital. Data of patients above 18 years were recorded after obtaining their informed consent. The National Formulary of India (NFI) and British National Formulary (BNF) guidelines were used as tools for evaluation of the prevalence of off-label drug use. Results: A total of 709 drugs were recorded from the prescription data of 205 patients collected in the duration of 2 months. The results reported 145 (20.45%) and 317 (44.71%) drugs as off-label as per the NFI and BNF, respectively. Prescriptions with minimum 1 off-label drug use were 78.05% – BNF and 46.83% – NFI. The indication was one of the most common causes of drugs being off-label. Out of the total 317 off-label drug uses reported, 84 were unlicensed drug use as per the BNF. There is strong and positive correlation established between the age of the patients, number of drugs prescribed, and total off-label drugs prescribed per patient in the given study. The most common off-label drug use noted was with clonazepam and amitriptyline. Conclusion: Off-label prescriptions practice is common in the field of neurology. [ABSTRACT FROM AUTHOR]

Objective: Considering emerging safety concerns involving otic quinolones, we assessed the extent of otic quinolone use for questionable indications.Study Design: Descriptive cross-sectional study of a national sample of privately insured patients.Setting: Outpatient encounters in the United States.Subjects and Methods: Children and adults with outpatient pharmacy-dispensing claims for new prescriptions of otic or ophthalmic quinolones in 2017 were identified within the IBM MarketScan Commercial Claims & Encounters and the Medicare Supplemental Database. Each dispensing ≥30 days apart constituted a unique episode. Only claims with supporting ear-related diagnoses on outpatient encounters ±3 days of dispensing were considered. Ophthalmic drops were excluded if eye-related diagnoses were found ±30 days. Prescribing was classified as appropriate, questionable, or undetermined.Results: We found 214,897 episodes in 200,270 patients. Adults were twice as likely as children to have otic treatment with questionable indications (6.2% vs 3.0%). Sensitivity analyses with broader time windows to ascertain diagnoses showed similar proportions of questionable use. Otalgia and cerumen impaction constituted 90% of questionable indications. Family physicians (6.8%) and internists (8.0%) had higher percentages of questionable use than other specialties.Conclusion: Based on the demonstrated risks of quinolone ear drops, opportunities exist to decrease otic quinolone use, especially in adults. [ABSTRACT FROM AUTHOR]

The purpose of this essay is to inform others that it is possible to survive breast cancer with brain metastases. The second author is the subject patient and a long-term survivor of systemic metastatic breast cancer with numerous brain metastases (corresponding to 8% survivor group). We credit her survival to a combination of (1) medicine as practiced by an excellent oncologist with whom we developed a partnership to manage the patient's health, (2) our informed exploration of the available scientific knowledge including a review of scientific research articles that go beyond conventional care, and (3) the patient's supplementation with numerous repurposed drugs and other substances reported to have antitumor properties. Alongside her conventional treatment (the medical standard of care), it seems likely that this supplementation has been a key factor in the patient's long-term survival. We also point out that the lack of follow-up magnetic resonance imaging brain scans for early detection of brain metastases poses substantial risks for patients with HER2+ metastatic breast cancer in non–central nervous system locations. Thus, we suggest that research be conducted on such early detection for possible inclusion in the recommendations for the medical standard of care. Finally, medical doctors and also patients with backgrounds in biological science may wish to consider potential options and advantages of repurposed drugs and other substances reported in scientific publications when the medical standard of care has limited options for advanced cancer and other severe chronic health conditions. However, any efforts along this line by patients should be in collaboration with their medical doctors. [ABSTRACT FROM AUTHOR]