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1.
Artigo em Inglês | MEDLINE | ID: mdl-34639747

RESUMO

Off-label use of drugs is widely known as unapproved use of approved drugs, and it can be perceived as a relatively simple concept. Even though it has been in existence for many years, prescribing and dispensing of drugs in an off-label regimen is still a current issue, triggered especially by unmet clinical needs. Several therapeutic areas require off-label approaches; therefore, this practice is challenging for prescribing physicians. Meanwhile, the regulatory agencies are making efforts in order to ensure a safe practice. The present paper defines the off-label concept, and it describes its regulation, together with several complex aspects associated with clinical practices regarding rare diseases, oncology, pediatrics, psychiatry therapeutic areas, and the safety issues that arise. A systematic research of the literature was performed, using terms, such as "off-label", "prevalence", "rare diseases", "oncology", "psychiatry", "pediatrics", and "drug repurposing". There are several reasons for which off-label practice remains indispensable in the present; therefore, efforts are made worldwide, by the regulatory agencies and governmental bodies, to raise awareness and to ensure safe practice, while also encouraging further research.


Assuntos
Médicos , Psiquiatria , Criança , Humanos , Oncologia , Uso Off-Label , Prevalência
3.
Rinsho Ketsueki ; 62(8): 978-987, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497238

RESUMO

Recurrence in acute myeloid leukemia (AML) is a major barrier in patients who achieve complete remission after induction of remission and consolidation therapy and desire long-term survival. Allogeneic hematopoietic stem cell transplantation lowers recurrence risk in patients; however, recurrence is common even after transplantation. Many maintenance therapies for AML aim to lower recurrence risk; therefore, research has focused on identifying drugs with a tolerable adverse-effect profile. Thus far, many trials of cytotoxic anticancer drugs used in maintenance therapy have showed no improvement in survival rates. In contrast, recent studies on immunomodulation, epigenetics, molecular-targeted drugs, etc. have demonstrated promising results. Therefore, we plan to review various maintenance therapies, such as immunotherapy, demethylating agents, and targeted therapies (including fms-like tyrosine kinase 3 inhibitors in particular) based on the current evidence. Moreover, we describe a new strategy that incorporates the assessment of measurable minimal residual disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Preparações Farmacêuticas , Humanos , Japão , Leucemia Mieloide Aguda/tratamento farmacológico , Uso Off-Label , Indução de Remissão
5.
J Comp Eff Res ; 10(14): 1045-1053, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34525842

RESUMO

Aim: To describe trends in off-label antipsychotic use among Texas Medicaid adults and examine whether demographic and clinical characteristics were associated with off-label use. Methods: Three diagnostic groups (i.e. no diagnosis, on label and off-label) were created based on mental health disorder diagnoses and related antipsychotic prescriptions. Results: During 2013-2016, the prevalence of off-label antipsychotic use decreased from 22.5% to 17.4% and the proportions of no mental health diagnosis remained stable (7.3-9.4%). Patients aged ≥25 years and second-generation antipsychotic users had significantly lower odds of receiving antipsychotics off-label or with no diagnosis. Conclusion: Compared with previous Medicaid database studies, the proportions of off-label antipsychotic use and antipsychotic use with no concurrent psychiatric diagnosis were notably lower.


Assuntos
Antipsicóticos , Transtornos Mentais , Adulto , Antipsicóticos/uso terapêutico , Humanos , Medicaid , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Uso Off-Label , Texas/epidemiologia , Estados Unidos/epidemiologia
7.
Ned Tijdschr Geneeskd ; 1652021 07 01.
Artigo em Holandês | MEDLINE | ID: mdl-34346574

RESUMO

The Dutch Medicines Act and the Medical Treatment Contracts Act (WGBO) form the legal framework for off-label prescribing. These acts are complemented with position statements and guidelines of professional organizations. However, this legal framework is not yet sufficiently embedded in daily practice. The explicit translation of the legal conditions into practical stepwise guidance can therefore provide important guidance when prescribing off-label. This article describes a step-by-step guide for responsible off-label prescribing. The step-by-step guide ensures that decisions about off-label use of drugs are made based on a deliberate and explicit consideration of the unmet medical need and alternative treatment strategies against the potential risks and benefits for the individual patient. In addition, the step-by-step guide ensures the correct provision of information to patients. In this way, the step-by-step guide enables the doctor to meet the regulatory requirements on the off-label prescription of drugs. In addition, we need better information provision on off-label use and professional consensus on information and consent obligation in order to be able to prescribe even more effectively off-label.


Assuntos
Uso Off-Label , Médicos , Humanos
8.
Ned Tijdschr Geneeskd ; 1652021 07 01.
Artigo em Holandês | MEDLINE | ID: mdl-34346661

RESUMO

When patients are treated with a drug that is not registered for the intended indication the prescriber must inform the patient on the benefits and risks of this off-label prescription. In the patient file the prescriber should make a note that the patient was informed. In daily practice prescribers are reluctant to do this, with the motivation that informing patients on benefits and risks of pharmacotherapy is done for all drug treatments, and that this is not different for off-label prescriptions.


Assuntos
Prescrições de Medicamentos , Uso Off-Label , Humanos , Padrões de Prática Médica , Prescrições , Rotulagem de Produtos
9.
Drug Des Devel Ther ; 15: 3349-3378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34376971

RESUMO

Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.


Assuntos
Assistência Ambulatorial , Antibacterianos/uso terapêutico , COVID-19 , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Uso Off-Label , Participação do Paciente , Teicoplanina/análogos & derivados , Algoritmos , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Teicoplanina/efeitos adversos , Teicoplanina/farmacocinética , Teicoplanina/uso terapêutico , Resultado do Tratamento
10.
Crit Rev Ther Drug Carrier Syst ; 38(3): 75-115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34348019

RESUMO

The outbreak of novel coronavirus (nCoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in December 2019 in Wuhan, China, has posed an international public health emergency worldwide and forced people to be confined in their homes. This virus is of high-risk category and is declared a pandemic by the World Health Organization (WHO). The worldwide researchers and various health professionals are working together to determine the best way to stop its spread or halt this virus's spread and circumvent this pandemic condition threatening millions of human lives. The absence of definitive treatment is possible to explore to reduce virus infection and enhance patient recovery. Along with off-label medicines, plasma therapy, vaccines, the researchers exploit the various plants/herbs and their constituents to effectively treat nCoV infection. The present study aimed to present brief and most informative salient features of the numerous facts regarding the SARS-CoV-2, including the structure, genomic sequence, recent mutation, targeting possibility, and various hurdles in research progress, and off-labeled drugs, convalescent plasma therapy, vaccine and plants/herbs for the treatment of coronavirus disease-2019 (COVID-19). Results showed that off-labeled drugs such as hydroxychloroquine, dexamethasone, tocilizumab, antiviral drug (remdesivir, favipiravir), etc., give positive results and approved for use or approved for restricted use in some countries like India. Future research should focus on these possibilities that may allow the development of an effective treatment for COVID-19.


Assuntos
Antivirais/farmacologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/tratamento farmacológico , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/uso terapêutico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Quimioterapia Combinada/métodos , Humanos , Terapia de Alvo Molecular/métodos , Mutação , Uso Off-Label , Pandemias/prevenção & controle , Extratos Vegetais/uso terapêutico , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Resultado do Tratamento , Proteínas Estruturais Virais/antagonistas & inibidores , Proteínas Estruturais Virais/genética , Proteínas Estruturais Virais/metabolismo
11.
Mult Scler ; 27(9): 1403-1410, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34304636

RESUMO

BACKGROUND: Off-label disease-modifying therapies (DMTs) for multiple sclerosis (MS) are used in at least 89 countries. There is a need for structured and transparent evidence-based guidelines to support clinical decision-making, pharmaceutical policies and reimbursement decisions for off-label DMTs. OBJECTIVES/RESULTS: The authors put forward general principles for the ethical use of off-label DMTs for treating MS and a process to assess existing evidence and develop recommendations for their use. CONCLUSION: The principles and process are endorsed by the World Federation of Neurology (WFN), American Academy of Neurology (AAN), European Academy of Neurology (EAN), Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) and Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), and we have regularly consulted with the Brain Health Unit, Mental Health and Substance Use Department at the World Health Organization (WHO).


Assuntos
Esclerose Múltipla , Neurologia , Humanos , Esclerose Múltipla/tratamento farmacológico , Uso Off-Label , Estados Unidos
12.
Eur J Pharmacol ; 908: 174374, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34303662

RESUMO

The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.


Assuntos
COVID-19/tratamento farmacológico , Cloroquina/farmacologia , Fosfatase 1 de Especificidade Dupla/genética , Glucocorticoides/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Adulto , Idoso , COVID-19/patologia , COVID-19/virologia , Estudos de Casos e Controles , Células Cultivadas , Cloroquina/uso terapêutico , Conjuntos de Dados como Assunto , Regulação para Baixo/efeitos dos fármacos , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/genética , Sinergismo Farmacológico , Fosfatase 1 de Especificidade Dupla/metabolismo , Fibroblastos , Glucocorticoides/uso terapêutico , Voluntários Saudáveis , Humanos , Pulmão/citologia , Pulmão/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Pessoa de Meia-Idade , Nasofaringe/virologia , Uso Off-Label , Cultura Primária de Células , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade
14.
BMC Psychiatry ; 21(1): 375, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315410

RESUMO

BACKGROUND: The off-label use of antipsychotic medications is common in many countries, and the extent of such use in psychiatric inpatients in China has not been sufficiently studied. The purpose of this study was to survey the incidence and examine the correlates of off-label antipsychotic use in a large, nationally-representative sample in China. METHODS: This study included discharged psychiatric patients between March 19 and 31, 2019 from 41 tertiary psychiatric hospitals across 29 provinces in China. Their socio-demographic and clinical data were collected and analyzed. RESULTS: After excluding patients with schizophrenia spectrum disorder or bipolar disorder, 981 patients were included in the analysis. Overall, antipsychotics were prescribed to 63.2% (95%CI 60.2-66.2%) of the sample. Antipsychotics were used in a wide spectrum of psychiatric disorders, with the rate being the highest among patients with dissociative (conversion) disorders (89.9, 95%CI 83.0-94.8%), organic mental disorders (81.7, 95%CI 73.1-88.7%), dementia (79.0,95%CI 67.8-87.9%), obsessive-compulsive disorder (77.8, 95%CI 55.7-92.5%), mental disorders due to psychoactive substances (75.3,95%CI 64.7-84.2%), behavioural and emotional disorders with onset usually occurring in childhood and adolescence (71.4, 95%CI 45.5-90.1%), somatoform disorders (63.2, 95%CI 40.8%-82..2%), major depression disorder (53.7,95%CI 48.8-58.6%), anxiety disorder (38.8,95%CI 30.5-47.7%), and insomnia (25.0, 95%CI 8.5-28.9%). The top three most commonly used antipsychotics were olanzapine (29.1%), quetiapine (20.3%) and risperidone (6.8%), and their corresponding average doses were 9.04 ± 5.80 mg/day, 185.13 ± 174.72 mg/day, and 2.98 ± 1.71 mg/day, respectively. A binary logistic regression showed that younger age, having the Employee Health Insurance or Residents Health Insurance, having psychotic symptoms and requiring restraint during hospitalization were significantly associated with off-label use of antipsychotics. CONCLUSION: Off-label use of antipsychotics is very common in psychiatric inpatients in China, mainly with moderate-dose use of single agents. However, the efficacy and safety of this practice is uncertain for many diagnoses and for the elderly. Clinicians should be cautious about this practice while waiting for more research data.


Assuntos
Antipsicóticos , Adolescente , Idoso , Antipsicóticos/uso terapêutico , China/epidemiologia , Humanos , Pacientes Internados , Uso Off-Label , Risperidona
15.
Clin Pharmacol Ther ; 110(4): 1127-1135, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110632

RESUMO

Public knowledge-based application ("Kouchi-shinsei" in Japanese) is unique to Japan, implemented to eliminate the off-label use of unapproved indications, dosages, and administrations because of drug lag. The guidance for public knowledge-based application was issued in 1999. This study comprehensively investigated the trends of items approved by public knowledge-based application in Japan during the last 2 decades. Prescription drugs approved from January 2000 to December 2019 were surveyed. In Japan, 1,855 drugs were approved within the target survey period. Among them, 219 (11.8%) were approved by public knowledge-based application. Considering the changes in the number of items approved by public knowledge-based application over the years, the number of items approved in 2000 was 7, reaching a maximum of 34 items in 2011, and decreased after that, 8 items were approved in 2019. The regulatory characteristics of drugs approved by public knowledge-based application and those of other drugs were compared. By public knowledge-based application, more anticancer and pediatric drugs were approved (P < 0.001), and only one drug for orphan diseases was approved (P < 0.001). In addition, the review time of public knowledge-based applications was significantly shorter than that of normal applications regardless of time point. The approval system using public knowledge-based application began in 2000, following issuance of the "Guidance for off-label use of prescription drugs." Furthermore, the approved items were mostly drugs for cancer, infectious diseases, and pediatric drugs. We anticipate the promotion of public knowledge-based application to accommodate the approval of drugs for orphan diseases.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Uso Off-Label/legislação & jurisprudência , Medicamentos sob Prescrição , Anti-Infecciosos , Antineoplásicos , Fármacos Cardiovasculares , Fármacos do Sistema Nervoso Central , Ensaios Clínicos como Assunto , Formas de Dosagem , Fármacos Gastrointestinais , Humanos , Japão , Bases de Conhecimento , Compostos Radiofarmacêuticos , Agentes Urológicos , Vacinas
16.
Clin Pharmacol Ther ; 110(4): 952-965, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34145575

RESUMO

A drug is granted a license for use after a thorough assessment of risks and benefits based on high-quality scientific proof of its efficacy and safety. Many drugs that are relevant to children are not licensed for use in this population implying that a thorough assessment of risks and benefits in the pediatric population has not been made at all, implying a negative risk-benefit balance in children, or implying insufficient information to establish the risk-benefit balance. Use of drugs without positive assessment of risks and benefits exposes children to potential lack of efficacy, unknown toxicity, and harm. To aid guideline committees and individual prescribers, we here present a tutorial of the Benefit and Risk Assessment for Off-label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off-label drug use, including a clinical pharmacological based approach to age-appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off-label use of ondansetron for gastroenteritis-induced nausea and vomiting. The framework could also guide decisions on off-label use in other special populations (e.g., pregnant women, elderly, obese, or critically ill patients) where off-label drug use is frequent, thereby contributing to effective and safe pharmacotherapy.


Assuntos
Uso Off-Label , Preparações Farmacêuticas , Medição de Risco/métodos , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido
17.
Biomolecules ; 11(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066168

RESUMO

BACKGROUND: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising therapy candidates, such as dasatinib, a Lyn-kinase inhibitor, have been identified. METHODS: RBCs of two ChAc patients during and after dasatinib treatment were characterized by the ESR, clinical hematology parameters and the 3D shape classification in stasis based on an artificial neural network. Furthermore, mathematical modeling was performed to understand the contribution of cell morphology and cell rigidity to the ESR. Microfluidic measurements were used to compare the RBC rigidity between ChAc patients and healthy controls. RESULTS: The mechano-morphological characterization of RBCs from two ChAc patients in an off-label treatment with dasatinib revealed differences in the ESR and the acanthocyte count during and after the treatment period, which could not directly be related to each other. Clinical hematology parameters were in the normal range. Mathematical modeling indicated that RBC rigidity is more important for delayed ESR than cell shape. Microfluidic experiments confirmed a higher rigidity in the normocytes of ChAc patients compared to healthy controls. CONCLUSIONS: The results increase our understanding of the role of acanthocytes and their associated properties in the ESR, but the data are too sparse to answer the question of whether the ESR is a suitable biomarker for treatment success, whereas a correlation between hematological and neuronal phenotype is still subject to verification.


Assuntos
Acantócitos/efeitos dos fármacos , Biomarcadores/sangue , Sedimentação Sanguínea/efeitos dos fármacos , Dasatinibe/uso terapêutico , Eritrócitos/efeitos dos fármacos , Neuroacantocitose/tratamento farmacológico , Acantócitos/patologia , Adulto , Forma Celular/efeitos dos fármacos , Humanos , Masculino , Neuroacantocitose/sangue , Neuroacantocitose/patologia , Uso Off-Label , Inibidores de Proteínas Quinases/uso terapêutico
18.
Psychiatr Serv ; 72(9): 1031-1039, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074139

RESUMO

OBJECTIVE: Off-label utilization of second-generation antipsychotic medications may expose patients to significant risks. The authors examined the prevalence, temporal trends, and factors associated with off-label utilization of second-generation antipsychotics among publicly insured adults. METHODS: A retrospective repeated panel was used to examine monthly off-label utilization of second-generation antipsychotics among fee-for-service Medicare, Medicaid, and dually eligible White, Black, and Latino adult beneficiaries filling prescriptions for second-generation antipsychotics in California, Georgia, Mississippi, and Oklahoma from July 2008 through June 2013. RESULTS: Among 301,367 users of second-generation antipsychotics, between 36.5% and 41.9% had utilization that was always off-label. Payer did not modify effects of race-ethnicity on off-label utilization. Compared with Whites, Blacks had lower monthly odds of off-label utilization in all four states, and Latinos had lower odds of utilization in California and Georgia. Payer was associated with off-label utilization in California, Mississippi, and Oklahoma. California Medicaid beneficiaries were 1.12 (95% confidence interval=1.10-1.13) times as likely as dually eligible beneficiaries to have off-label utilization. Off-label utilization increased relative to the baseline year in all states, but a downward trend followed in three states. CONCLUSIONS: Off-label utilization of second-generation antipsychotics was prevalent despite the drugs' cardiometabolic risks and little evidence of their effectiveness. The lower likelihood of off-label utilization among patients from racial-ethnic minority groups might stem from prescribers' efforts to minimize risks, given a higher baseline risk for these groups, or from disparities-associated factors. Variation among payers suggests that payer policies can affect off-label utilization.


Assuntos
Antipsicóticos , Adulto , Idoso , Antipsicóticos/uso terapêutico , Grupos Étnicos , Humanos , Medicaid , Medicare , Grupos Minoritários , Uso Off-Label , Estudos Retrospectivos , Estados Unidos
20.
Eur J Pediatr ; 180(9): 3067-3071, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34137919

RESUMO

Treatment of children with cancer requires access to and reimbursement of effective drugs. Children with haemato-oncological diseases are often treated according to established treatment recommendations or in the framework of late-phase clinical trials. These often involve the use of drugs authorised for adults but which, however, have been used for many years in paediatrics with no perspective of authorisation in children. In Belgium, medicines are predominantly reimbursed based on their authorised indication. As a consequence, many drugs used in paediatric haemato-oncology are used off-label, despite their status of 'standard of care'. As reimbursement is often not available, alternative ways for funding need to be explored, which causes a significant administrative burden for healthcare providers and emotional distress for the parents. Solutions to organise a systematic reimbursement of standard of care off-label used drugs are described.Conclusion: A number of structural solutions are proposed, and we hope that they might guide health authorities to provide a solution to the problem caused by the lack of reimbursement of some standard of care medicines for children with cancer. What is Known: • Off-label drug use is frequently observed in paediatric haemato-oncology and compromises-in some countries-reimbursement. What is New: • An estimation of the impact of non-reimbursed drugs in Belgium is provided. • Some solutions are presented to overcome this problem in Belgium.


Assuntos
Neoplasias , Pediatria , Preparações Farmacêuticas , Adulto , Bélgica , Criança , Humanos , Neoplasias/tratamento farmacológico , Uso Off-Label
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