Tomato lipidic extract plus selenium decrease prostatic hyperplasia, dihydrotestosterone and androgen receptor expression versus finasteride in rats.

PURPOSE: Evaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride. MATERIALS AND METHODS: 54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined. RESULTS: STE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate. CONCLUSIONS: These results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

Female-pattern hair loss: therapeutic update.

Female androgenetic alopecia or female-pattern hair loss (FPHL) is highly prevalent and has a great impact on the quality of life. The treatment is a routine challenge in dermatological practice, as many therapeutic options have a limited level of evidence and often do not meet patients expectations. Lack of knowledge of the pathogenesis of the hair miniaturization process and the factors that regulate follicular morphogenesis restricts the prospect of innovative therapies. There is also a lack of randomized, controlled studies with longitudinal follow-up, using objective outcomes and exploring the performance of the available treatments and their combinations. Topical minoxidil, which has been used to treat female pattern hair loss since the 1990s, is the only medication that has a high level of evidence and remains the first choice. However, about 40% of patients do not show improvement with this treatment. In this article, the authors critically discuss the main clinical and surgical therapeutic alternatives for FPHL, as well as present camouflage methods that can be used in more extensive or unresponsive cases.

Endocrine, prostatic vascular, and proapoptotic changes in dogs with benign prostatic hyperplasia treated medically or surgically.

Benign prostatic hyperplasia (BPH) is a disorder related to hormone imbalance, local angiogenesis, and prostate growth, which can be treated surgically (orchiectomy) or medically (most commonly with finasteride). However, finasteride therapy is not completely established in dogs regarding local action and posology. This study aimed to evaluate the effect of different doses of finasteride and orchiectomy on hormonal profile, prostate apoptosis, blood flow, and biometry in dogs with BPH. Dogs were assigned to the following groups: untreated, 0.1 mg, 0.2 mg, and 0.5 mg/kg/d of finasteride and orchiectomy. All dogs were assessed monthly: day 0 (before treatment), day 30, and day 60 and subjected to prostate B-mode and Doppler ultrasonography and hormonal analysis (testosterone and dihydrotestosterone). After 60 d, prostatic biopsy was performed for histology and immunohistochemical evaluation for apoptosis (caspase-3). On day 60, percentage reduction of prostatic volume was greater in orchiectomized dogs than that in finasteride groups, which, conversely, was greater than untreated dogs. On day 60, 0.2-mg finasteride, 0.5-mg finasteride, and orchiectomy groups had higher prostatic blood flow than 0.1-mg finasteride and untreated groups. In addition, both 0.5-mg finasteride and orchiectomy groups had an increase in prostate artery resistance. Orchiectomy significantly decreased androgen concentrations at 30 d onward, differing from the remaining groups. The orchiectomy group had lower caspase-3 immunostaining, however, not different from untreated and 0.5-mg finasteride. In conclusion, 0.5 mg/kg finasteride promoted more effective prostate apoptosis and hemodynamic effects among medical treatments, whereas orchiectomy caused prostate atrophy and sharp endocrine changes in dogs with BPH.

Reproductive and endocrinological effects of Benign Prostatic Hyperplasia and finasteride therapy in dogs.

Benign prostatic hyperplasia (BPH) is one of the most important reproductive disorders in aging dogs. Therapeutic measures include orchiectomy and pharmacological treatment, leading to reduction of prostate volume and clinical signs. One of the most common drugs used in BPH treatment is finasteride, but data regarding its possible side effects are scarce. Thus, the aim of this study was to evaluate the effects of BPH and short-term (2 months) finasteride therapy on clinical, endocrinological, and reproductive parameters in dogs. Dogs were allocated into four experimental groups: Non-affected (n = 5), BPH (n = 5), Non-Affected-Finasteride (n = 5) and BPH-Finasteride (n = 5) groups. Dogs were evaluated monthly during 2 months by a complete breeding soundness examination, B-mode ultrasound and Doppler ultrasonography of the testicular artery, hormonal profile (testosterone, estrogen and dihydrotestosterone) and oxidative profile of the prostatic fluid. After 2 months, dogs were gonadectomized and testicles were subjected to histologic analysis. Finasteride treatment reduced dihydrotestosterone concentrations, without negative influence on semen quality and also reverted testicular hemodynamics changes of BPH. On the other hand, BPH was accompanied by significant changes in testosterone and estrogen concentrations and semen quality, mainly related to sperm kinetics alterations. In conclusion, BPH dogs have important hormonal and sperm alterations, however, short-term finasteride treatment (2 months) was able to reduce overall effects of BPH, thus representing a method of therapy for BPH treatment.

Inflammatory pathway employed by Red Maca to treat induced benign prostatic hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a pathology characterised by an increase in prostate size associated with low urinary tract symptoms. Finasteride (F), a 5a-reductase inhibitor, is the standard treatment for BPH reducing prostate weight but also sexual desire. The Peruvian plant known as Red Maca (RM) (Lepidium meyenii) inhibits BPH in rats and mice. The aim of the study was to assess the inflammatory effect of RM and finasteride in rats with testosterone enanthate (TE)-induced BPH. Thirty rats were divided into 5 groups: Control, TE (50 mg/rat), TE + F (0.6 mg/kg), and two groups of TE + RM 40/80 (40 or 80 mg). After treatments, tumour necrosis factor alpha (TNFa), interleukin 4 (IL4) and interferon gamma (INFg) as well as testosterone and oestradiol were evaluated and inflammatory cells (neutrophils, mast cells and lymphocytes) in prostate were quantified. Red Maca and finasteride treatments decreased inflammatory cells counts in prostate, inhibiting TNFa by different pathways. Finasteride increased IL4 whereas Red Maca increased INFg. In conclusion, data suggest that finasteride acts on Th2 response by increasing IL4 in prostate, while Red Maca acts on Th1 response mediated by INFg.

Cost-Effectiveness of Combination Therapy Versus Monotherapy in Benign Prostatic Hyperplasia: A Colombian Experience.

OBJECTIVES: To estimate the incremental cost-effectiveness ratio of pharmacological treatment for benign prostatic hyperplasia from the payer's perspective. METHODS: The cost-effectiveness of 5 mg finasteride, 0.5 mg dutasteride, 10 mg alfuzosin, 10 mg terazosin, 0.4 mg tamsulosin, 4 mg doxazosin, and the combination therapy of 5 mg finasteride and 8 mg doxazosin was evaluated using a Markov model over a 30-year period. The costs were estimated using national tariffs and were reported in US dollars. Cost and effectiveness outcomes were discounted at a rate of 5% per year. Men (aged ≥40 years) with moderate to severe lower urinary tract symptoms and uncomplicated benign prostatic hyperplasia were included in the analysis. Outcomes included costs and quality-adjusted life-years. A probabilistic sensitivity analysis was performed on important parameters with Monte-Carlo simulation. RESULTS: Finasteride alone or in combination with doxazosin dominated all α-blockers. After excluding dominated alternatives, the incremental cost-utility ratio for combination therapy was $377 per quality-adjusted life-year, being a cost-effective alternative using the threshold of $15 000. Model results were robust to changes in costs, utility weights, and probabilities. Acceptability curves consistently demonstrated that the combination therapy was most likely cost-effective. CONCLUSIONS: The combination of finasteride and doxazosin is cost-effective compared with dutasteride, tamsulosin, terazosin, and alfuzosin in patients with benign prostatic hyperplasia with moderate or severe symptoms who are older than 40 years.

The corpus cavernosum after treatment with dutasteride or finasteride: A histomorphometric study in a benign prostatic hyperplasia rodent model.

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia (BPH) rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups: C, untreated control rats; C + D, control rats receiving dutasteride; C + F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats (SHRs); H + D, SHRs treated with dutasteride; and H + F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density (Sv) of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni's posttest. Groups C + D and C + F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C + D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H + D and H + F had less smooth muscle Sv than Group H. Group H + D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was greater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

Effects of benign prostatic hyperplasia and finasteride therapy on prostatic blood flow in dogs.

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate accompanied by an increase in prostatic blood perfusion and vascularization. The most indicated treatment is to perform orchiectomy, however, medical treatment with finasteride can be an option for breeding dogs or elderly animals with a critical health status. In dogs, the influence of medical treatment on prostatic hemodynamics is still unknown. Therefore, this study aimed to evaluate the effects of benign prostatic hyperplasia and finasteride therapy on hemodynamic and vascular features of the canine prostate. For this purpose, twenty dogs of different breeds, body weights (10-30 kg) and ages (5-13 years) were used, assigned for: Healthy-non treated group (n = 5), BPH-non treated group (n = 5), Healthy-finasteride treated group (n = 5) and BPH-finasteride treated group (n = 5). Dogs that presented hematospermia and at least one general clinical sign (tenesmus, hematuria or dysuria) were presumptively diagnosed with BPH. Dogs were evaluated ultrasonographycally by B-mode and Doppler of the prostatic artery in a monthly interval (day 0, 30 and 60) in order to measure prostate volume (PV), expected prostate volume (EPV), prostate vascularization score (scored as minimum, intermediary and maximum) and prostatic artery blood flow parameters with the use of spectral and color Doppler ultrasound. It was possible to observe a decrease in prostate vascularization score between Day 0 (intermediary degree) and 60 (minimum degree) in finasteride treated dogs. Moreover, non-treated dogs had higher score of vascularization at Day 60 compared to animals treated with finasteride, regardless of BPH diagnosis. Healthy-non treated animals presented higher peak systolic:diastolic velocity (S/D) than BPH-non treated dogs. Furthermore, BPH-non treated dogs had lower S/D than BPH-finasteride treated dogs. In 30 and 60 days, no difference on PV was observed between BPH-finasteride treated group and Healthy-non treated group. At day 60, no difference between PV and EPV was observed for the BPH-finasteride treated group. In conclusion, finasteride treatment reduces simultaneously the volume, local vascularization and blood flow of the prostate, thus, being considered an effective and additional choice of therapy for BPH. Moreover, the course of therapy in dogs can be followed by analyzing changes in prostatic artery.

Fractional non-ablative laser-assisted drug delivery leads to improvement in male and female pattern hair loss.

Androgenetic alopecia, also known as male and female pattern hair loss, is a very prevalent condition; however, approved therapeutic options are limited. Fractionated laser has been proposed to assist in penetration of topical medications to the cutaneous tissue. We present four cases of androgenetic alopecia that underwent treatment with a non-ablative erbium glass fractional laser followed by the application of topical finasteride 0,05% and growth factors including basic fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, and copper peptide 1%. During all laser treatment sessions, eight passes were performed, at 7 mJ, 3-9% of coverage and density of 120 mzt/cm2. A positive response was observed in all of the four patients. Photographs taken 2 weeks after the last session showed improvement in hair regrowth and density. No significant side effects were observed.

Hiperplasia prostática benigna em cães / Benign prostatic hyperplasia in dogs

A Hiperplasia prostática benigna (HPB) é uma patologia originada da próstata, única glândula sexual acessória em cães, que se desenvolve em animais de meia idade à idosos, não castrados, de etiologia ainda não muito bem compreendida. Esta revisão de literatura tem como objetivo discutir os sinais clínicos, formas de diagnóstico e de tratamento dessa enfermidade. A di-hidrotestosterona sérica é o principal hormônio que estimula o crescimento da próstata canina. Os principais sinais clínicos desta patologia são a perda de peso, disquezia, tenesmo, incontinência urinária, secreção uretral e hematúria. Para o diagnóstico desta prostatopatia é necessário um conhecimento rigoroso da anatomia, dos sinais clínicos, dos achados dos exames de palpação retal, ultrassonografia eradiografia abdominais, hemograma completo, perfil bioquímico, citologia do líquido prostático, exames histopatológicos da glândula e o uso de biomarcadores. Apesar do tratamento mais efetivo ser a orquiectomia, pode-se utilizar também para o tamento terapêutico a finasterida, o acetato de delmadiona, o osasterona ou a aplicação da Toxina Botulínica A (TB-A).

Benign Prostatic Hyperplasia (BPH) is a pathology originated from theprostate, the only accessory sexual gland in dogs, and its development occurs in older, uncastrated animals of unknown etiology. This literature review aims to discuss the clinical signs, forms of diagnosis and treatment this disease. Serum dihydrotestosterone is the main hormone that stimulates the growth of the canine prostate. The main clinical signs of this pathology involve weight loss, dyschezia, tenesmus, urinary incontinence, urethral secretion and hematuria. The diagnosis of canine prostate pathologies requires a thorough knowledge of anatomy and clinical signs, rectal palpation, ultrasonography and radiography, hematological analysis, biochemical profile, cytology of prostatic fluid, histopathological examination of prostate and the use of biomarkers, all help in the diagnosis of BPH. The most effective treatment is orchiectomy, but finasteride, delmadione acetate, osasterone or the application of Botulinum Toxin-A (TB-A) may also be used as treatment.

Hiperplasia prostática benigna em cães / Benign prostatic hyperplasia in dogs

A Hiperplasia prostática benigna (HPB) é uma patologia originada da próstata, única glândula sexual acessória em cães, que se desenvolve em animais de meia idade à idosos, não castrados, de etiologia ainda não muito bem compreendida. Esta revisão de literatura tem como objetivo discutir os sinais clínicos, formas de diagnóstico e de tratamento dessa enfermidade. A di-hidrotestosterona sérica é o principal hormônio que estimula o crescimento da próstata canina. Os principais sinais clínicos desta patologia são a perda de peso, disquezia, tenesmo, incontinência urinária, secreção uretral e hematúria. Para o diagnóstico desta prostatopatia é necessário um conhecimento rigoroso da anatomia, dos sinais clínicos, dos achados dos exames de palpação retal, ultrassonografia eradiografia abdominais, hemograma completo, perfil bioquímico, citologia do líquido prostático, exames histopatológicos da glândula e o uso de biomarcadores. Apesar do tratamento mais efetivo ser a orquiectomia, pode-se utilizar também para o tamento terapêutico a finasterida, o acetato de delmadiona, o osasterona ou a aplicação da Toxina Botulínica A (TB-A).(AU)

Benign Prostatic Hyperplasia (BPH) is a pathology originated from theprostate, the only accessory sexual gland in dogs, and its development occurs in older, uncastrated animals of unknown etiology. This literature review aims to discuss the clinical signs, forms of diagnosis and treatment this disease. Serum dihydrotestosterone is the main hormone that stimulates the growth of the canine prostate. The main clinical signs of this pathology involve weight loss, dyschezia, tenesmus, urinary incontinence, urethral secretion and hematuria. The diagnosis of canine prostate pathologies requires a thorough knowledge of anatomy and clinical signs, rectal palpation, ultrasonography and radiography, hematological analysis, biochemical profile, cytology of prostatic fluid, histopathological examination of prostate and the use of biomarkers, all help in the diagnosis of BPH. The most effective treatment is orchiectomy, but finasteride, delmadione acetate, osasterone or the application of Botulinum Toxin-A (TB-A) may also be used as treatment.(AU)

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge.

Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge

Abstract Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

Efectos adversos de finasteride: mitos y realidades. una revisión actualizada / Finasteride adverse effects: an update

Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

Androgenetic Alopecia: An Update of Treatment Options.

Androgenetic alopecia (AGA) is characterized by a non-scarring progressive miniaturization of the hair follicle in predisposed men and women with a pattern distribution. Although AGA is a very prevalent condition, approved therapeutic options are limited. This article discusses the current treatment alternatives including their efficacy, safety profile, and quality of evidence. Finasteride and minoxidil for male androgenetic alopecia and minoxidil for female androgenetic alopecia still are the therapeutic options with the highest level evidence. The role of antiandrogens for female patients, the importance of adjuvant therapies, as well as new drugs and procedures are also addressed.

[Finasteride adverse effects: An update]. / Efectos adversos de finasteride: mitos y realidades. Una revisión actualizada.

Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

Tratamento de hipersexualidade em pessoas com deficiência intelectual: uso da finasterida / Treatment of hypersexuality in people with intellectual disabilities: use of finasteride / Tratamiento de hipersexualidad en personas con discapacidad intelectual: utilización de la finasterida

SITUAÇÃO/ PROBLEMA: Trata-se da solicitação de esclarecimentos sobre a utilização de finasterida para o controle de comportamentos sexuais inadequados em indivíduos portadores de deficiência intelectual, indicação não constante em bula. A avaliação e compreensão do mecanismo de ação e das evidências sobre as indicações de uso do medicamento finasterida possibilita um melhor entendimento sobre sua aplicabilidade e relevância de seu fornecimento pelo Sistema Único de Saúde (SUS) para esses casos. MÉTODOS: Para a produção dessa Nota Técnica foram realizadas buscas na base de dados PUBMED, em dezembro de 2015 e janeiro de 2016. Também foi realizada busca nas agências reguladoras Food and Drug Administration (FDA) e European Medicines Agency (EMA), além da Agência Nacional de Vigilância Sanitária (ANVISA), para a verificação das indicações terapêuticas registradas para a finasterida. Por fim, consultaram-se livros especializados e bulas dos medicamentos e realizou-se busca manual para complemento das informações. TRATAMENTO MEDICAMENTOSO: O tratamento farmacológico pode ser dividido em duas categorias: a intervenção direta hormonal, que tenta reduzir os efeitos de hormônios sexuais, no caso a testosterona e a di-hidrotestosterona, e a intervenção indireta, que busca reduzir a agressividade, a impulsividade e os transtornos psiquiátricos, como depressão maior ou transtorno bipolar, que possam influenciar a desinibição sexual. Sajith et al (2008) reforçam que a terapia psicológica ainda permanece como o tratamento de escolha para o comportamento sexual inadequado para pacientes com e sem deficiência intelectual e destaca que a qualidade da base de evidências para a utilização de agentes farmacológicos nestes casos é insuficiente para justificar seu uso rotineiro na prática clínica. Se utilizados, devem ser parte de um tratamento mais abrangente e monitorados continuamente. Além disso, os autores deixam claro que as informações sobre o tratamento do comportamento sexual inadequado em pacientes com deficiência intelectual é muito limitada e que grande parte dos estudos avaliados não identificavam se os pacientes possuíam deficiência intelectual. Nesse contexto, a escolha do tratamento deve considerar as circunstâncias individuais, como a gravidade da deficiência intelectual do indivíduo, a capacidade de compreensão do consentimento informado para o tratamento e de relatar os possíveis efeitos adversos dos medicamentos, a disponibilidade de recursos para monitorar o tratamento, a presença de sintomas psiquiátricos como comorbidades e os riscos apresentados pelo indivíduo para si e para os outros (SAJITH et al, 2008; OZKAN et al, 2008). A testosterona e seu metabólito di-hidrotestosterona, hormônios andrógenos, são fundamentais para o desenvolvimento e manutenção das características sexuais masculinas, na regulação da sexualidade, da agressão, da cognição e da personalidade (SAJITH et al., 2008). A finasterida é um medicamento inibidor específico 5-α-redutase, especialmente a do tipo II, enzima responsável pela conversão da testosterona em diidrotestosterona. CONSIDERAÇÕES FINAIS: conclui-se que a finasterida é indicada para o tratamento da Hiperplasia Prostática Benigna e Alopécia Androgênica, possuindo registro sanitário vigente apenas para essas condições. Considerando o uso investigativo e não constante em bula (off-label), a literatura apresenta como possíveis indicações da finasterida a monoterapia adjuvante após prostatectomia radical no tratamento do câncer de próstata e o hirsutismo feminino. Não foram encontrados estudos que evidenciem a utilização da finasterida para o tratamento comportamento sexual inadequado em indivíduos portadores de deficiência intelectual ou homens em geral. Além de não apresentar respaldo em bula para este uso, a finasterida é contra indicada para o uso em crianças e pode ser inefetiva ou pouco efetiva, tendo em vista a natureza incomum dos efeitos adversos apresentados sobre a sexualidade. O único medicamento com indicação em bula para o tratamento de desvios sexuais (comportamento sexual inapropriado; hipersexualidade) é o acetato de ciproterona, que pode apresentar efeitos adversos graves e comuns como a hepatotoxicidade. Ressalta-se que a terapia psicológica ainda permanece como o tratamento de escolha para o comportamento sexual inadequado em pacientes com deficiência intelectual. As evidências para a utilização de agentes farmacológicos nestes casos são limitadas e insuficientes para justificar seu uso rotineiro na prática clínica. O uso de terapia farmacológica deve ser parte de um tratamento mais abrangente, com necessidade de monitoramento contínuo.(AU)