Estudos.

Transcription

1 Estudos

2 DUTASTERIDA Inibição enzimática dupla: HPB e alopecia DESCRIÇÃO Dutasterida, inibidor duplo da 5 α-redutase. MECANISMO DE AÇÃO A Dutasterida atua inibindo as duas isoenzimas (tipo 1 e 2) que são responsáveis pela conversão da testosterona a 5 α-diidrotestosterona (DHT). O DHT é o principal responsável pela alopecia androgenética no homem e também a hiperplasia prostática benigna (HPB). Dessa forma a Dutasterida promove redução da queda de cabelo, diminuição do tamanho da próstata e redução do risco de retenção urinária. INDICAÇÕES Tratamento e prevenção da HPB; Melhora do fluxo urinário; Tratamento da alopecia androgenética. DOSE USUAL Recomendação oral de 0,5 mg de Dutasterida ao dia. SUGESTÕES DE FÓRMULAS Dutasterida...0,025% Finasterida... 0,05% Minoxidil... 2% Espumil qsp ml Modo de uso: 1 pump, 1 ou 2 vezes ao dia no couro cabeludo. Massagear até a completa absorção. Indicação: tratamento da alopecia androgenética. Dutasterida... 0,5 mg Tansulosina... 0,4 mg Modo de uso: 1 dose ao dia, 30 minutos depois da refeição. Indicação: tratamento HPB e melhora do fluxo urinário. PRINCIPAIS REFERÊNCIAS LACY F.C.; ARMSTRONG L.L.; GOLDMAN M.P.; LANCE L.L. Drug Information Handbook. American Pharmacists Association. Lexi-Comp. 23ª edição, TSUNEMI, Y. et al. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. The Journal of Dermatology. doi: / Disponível em:< Acesso em: 29/06/2016, às 14:15.

3 DUTASTERIDA ESTUDOS CLÍNICOS Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA. Background.We examined the efficacy of a new regimen to treat AGA, with attention to male patients who are atopic. Objective. To assess the efficacy of a four-part regimen for the treatment of AGA in atopic and nonatopic patients. NuH Hair is a novel topical combination of finasteride, dutasteride, and minoxidil, which is blended in a hypoallergenic lotion. The other three components included Rogaine foam, Propecia, and ketoconazole shampoo. Methods. A prospective pilot study was conducted in 15 patients. All patients were assessed for the presence of atopy. Each patient served as their own control. All patients were treated specifically with NuH Hair and were given the option to add any of the other components of the protocol to their regimen. Photographs were taken of each patient s scalp at months 0, 1, 3, 6, and 9. Results. All 15 patients demonstrated significant growth of hair. In those patients who utilized all 4 components, significant growth was achieved in as little as 30 days. In those patients who choose only to utilize NuH Hair, significant growth was demonstrated after 3 months. Conclusion. Aggressively treating AGA achieves significant and rapid growth of new hair. This is effective in atopic and nonatopic male patients. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. BACKGROUND: Dihydrotestosterone is the main androgen causative of androgenetic alopecia, a psychologically and physically harmful condition warranting medical treatment. OBJECTIVE: We sought to compare the efficacy and safety of dutasteride (type 1 and 2 5-alpha reductase inhibitor) with finasteride (type 2 5-alpha reductase inhibitor) and placebo in men with androgenetic alopecia. METHODS: Men aged 20 to 50 years with androgenetic alopecia were randomized to receive dutasteride (0.02, 0.1, or 0.5 mg/d), finasteride (1 mg/d), or placebo for 24 weeks. The primary end point was hair count (2.54-cm diameter) at week 24. Other assessments included hair count (1.13-cm diameter) and width, photographic assessments (investigators and panel), change in stage, and health outcomes. RESULTS: In total, 917 men were randomized. Hair count and width increased dose dependently with dutasteride. Dutasteride 0.5 mg significantly increased hair count and width in a 2.54-cm diameter and improved hair growth (frontal view; panel photographic assessment) at week 24 compared with finasteride (P =.003, P =.004, and P =.002, respectively) and placebo (all P <.001). The number and severity of adverse events were similar among treatment groups. LIMITATIONS: The study was limited to 24 weeks. CONCLUSIONS: Dutasteride increased hair growth and restoration in men with androgenetic alopecia and was relatively well tolerated. Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia. We report on a 47-year-old man who was initially treated with finasteride for androgenetic alopecia. Despite continuous treatment, after year 4 his hair density was not as good as at year 2, and low-dose dutasteride at 0.5 mg/week was added to the finasteride therapy. This resulted in a dramatic increase in his hair density, demonstrating that combined therapy with finasteride and dutasteride can improve hair density in patients already taking finasteride.

4 Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hair transplantation. A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months posttransplantation. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5- α-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT , GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population. The effectiveness of finasteride and dutasteride used for 3 years in women with androgenetic alopecia. BACKGROUND: The effectiveness of finasteride and dutasteride in women with androgenetic alopecia has been the subject of debate. AIM: To evaluate the effectiveness of finasteride and dutasteride on hair loss in women with androgenetic alopecia over a period of 3 years. METHODS: From a database containing systematically retrieved data on 3500 women treated for androgenetic alopecia between 2002 and 2012 with finasteride 1.25 mg or dutasteride 0.15 mg, a random sample stratified for age and type of medication was taken to yield 30 women in two age categories: below and above 50 years, and for both medications. Hair thickness of the three thinnest hairs was measured from standardized microscopic images at three sites of the scalp at the start of the treatment and after 3 years of continuous medication intake. The macroscopic images were evaluated independently by three European dermatologists/hair experts. The diagnostic task was to identify the image displaying superior density of the hair. RESULTS: Both age categories showed a statistically significant increase in hair thickness from baseline over the 3-year period for finasteride and dutasteride (signed rank test, P=0.02). Hair thickness increase was observed in 49 (81.7%) women in the finasteride group and in 50 (83.3%) women in the dutasteride group. On average, the number of post-treatment images rated as displaying superior density was 124 (68.9%) in the finasteride group, and 118 (65.6%) in the dutasteride group. Dutasteride performed statistically significantly better than finasteride in the age category below 50 years at the central and vertex sites of the scalp. CONCLUSIONS: Finasteride 1.25 mg and dutasteride 0.15 mg given daily for 3 years effectively increased hair thickness and arrested further deterioration in women with androgenetic alopecia.

5 Specific antigen prostatic changes during treatment with finasteride or dutasteride for benign prostatic hyperplasia. The aim of this paper was to compare and analyze the therapeutic effects and PSA variation levels with treatment with finasteride-tamsulosin and dutasteride-tamsulosin for benign prostatic hyperplasia for 2 years and the risk to developing prostate cancer for patients with PSA<4 ng/ml. We retrospectively investigated 288 patients who suffered from BPH and PSA>4 ng/ml between January 2003 and July For treatment groups, we divided the patients into two groups: one was treated with tamsulosin and finasteride and the other with tamsulosin and dutasteride. At the beginning of treatment, the patients underwent transrectal ultrasonography and prostate mapping, measurement of urine flow rate, PSA, and International Prostate Symptom Score (IPSS). A total of 288 patients were able to be. Both finasteride and dutasteride rduced PSA and prostate volume significantly. The comparison between the 2 groups showed a significant difference at 3 months for IPSS; uroflussimetry and prostate volume in the dutasteride group, but at 6 months did not differ significantly between the groups. Patients with a PSA reduction more than half presented a good response and didn't request surgical theraphy. 5 alpha Reductase inhibitors for BPH treatment reduced PSA and prostate volume significantly after 6 months of theraphy and after 3 months only for dutasteride. PSA reduction is directly correlated with response to theraphy. Didn't were evidenced statistically differences on prostate cancer presence during theraphy. 5α-Reductase inhibitors in androgenetic alopecia. PURPOSE OF REVIEW: The authors will review the current literature on efficacy and safety of 5-alpha reductase inhibitors (5αRIs) for androgenetic alopecia (AGA). RECENT FINDINGS: The 5αRI finasteride and dutasteride are effective in treating AGA and promoting hair regrowth. 5αRI can be given orally, topically and more recently through mesotherapy. However, there has been an increasing concern about permanent sexual adverse events such as impotence and infertility. Most of these reports are published as case reports, and two studies reporting persistent sexual side-effects after discontinuation of finasteride had serious method limitations, as patients were recruited from a website. To our knowledge, permanent sexual adverse events have yet to be published in higher quality studies, such as randomized controlled trials. Although patients treated with 5αRIs have an increased incidence of sexual adverse events, these events decrease if discontinued or over time with continued therapy. SUMMARY: Sexual side-effects are uncommon and resolve spontaneously in most patients even without discontinuing therapy. Significant effort is underway to find delivery systems that optimize delivery and reduce systemic absorption of topical 5αRs including hydroxypropyl chitosan and liposomal and nanoparticulate systems. Effect of dutasteride 0.5 mg/d in men with androgenetic alopecia recalcitrant to finasteride. BACKGROUND: Finasteride at a dose of 1 mg/d has been reported to show no significant improvement in 30-50% of patients with androgenetic alopecia (AGA). Dutasteride, a dual inhibitor of both type I and type II 5 alpha-reductase, inhibits the conversion of testosterone to dihydrotestosterone, which is the key contributor of AGA. MATERIALS AND METHODS: Our aim is to evaluate clinical efficacy and tolerability of dutasteride in men with AGA who do not show clinical improvement to the conventional finasteride treatment. A total of 35 Korean men with AGA who had not shown significant clinical improvement when treated with finasteride 1 mg/d for at least six months received dutasteride at a dose of 0.5 mg/d for six months. Efficacy was evaluated by global photograph assessment and phototrichogram. Safety assessment was performed through physical examination and adverse event report. RESULTS: Of the 31 patients who completed the treatment, 24 patients (77.4%) were improved by the global photography (17 were slightly, six moderately, and one markedly improved) compared with the post-finasteride

6 treatment. There was no significant change in seven patients (22.6%), and aggravation was not reported. Hair density and thickness significantly increased by 10.3% (87 ± ± 12/cm(2)) and 18.9% (0.053 ± ± mm), respectively, in phototrichogram assessment. Side effects included transient sexual dysfunction in six patients (17.1%). CONCLUSIONS: Dutasteride is suggestive to be an alternative treatment option to patients with AGA who do not clinically respond to finasteride in six months. The efficacy and safety of 5α-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefit-risk assessment of finasteride and dutasteride. INTRODUCTION: In the light of post-marketing reports of persistent sexual dysfunction with the use of finasteride, analysis of the extent of risk associated with 5α-reductase inhibitor treatment for androgenetic alopecia (AGA) is warranted. This study sought to evaluate the efficacy of 5α-reductase inhibitors using the outcomes hair count, global photographic assessment and patient self-assessment and evaluate the benefits of treatment versus the risk of global sexual dysfunction. METHODS: A systematic review identified all relevant randomized controlled trials of finasteride 1 mg, 5 mg and dutasteride 0.5 mg. The efficacy outcome hair count was analyzed using pair-wise meta-analysis, while the efficacy outcomes global photographic assessment and patient self-assessment as well as the safety outcome global sexual dysfunction were analyzed through network meta-analyses. A benefit-risk assessment was also performed. RESULTS: The active interventions were not significantly different than each other in efficacy and were not significantly different from placebo in eliciting sexual dysfunction. Benefit-risk analysis resulted in an arbitrary ranking due to the lack of statistically significant difference between active treatments. DISCUSSION: Analysis results reiterate the efficacy and safety of 5α-reductase inhibitors for the treatment of AGA and may support the approval of dutasteride 0.5 mg as an additional treatment option, following further study. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. BACKGROUND: Dutasteride (Avodart) is a dual inhibitor of both type I and type II 5 alpha reductases, and thus inhibits conversion of testosterone to dihydrotestosterone, a key mediator of male pattern hair loss. OBJECTIVES: The aim of this randomized double-blind phase III study was to compare the efficacy, safety, and tolerability of dutasteride (0.5 mg) and placebo for 6 months of treatment in male patients with male pattern hair loss. METHODS: A total of 153 men, 18 to 49 years old, were randomized to receive 0.5 mg of dutasteride or placebo daily for 6 months. Efficacy was evaluated by the change of hair counts, subject assessment, and photographic assessment by investigators and panels. RESULTS: Mean change of hair counts from baseline to 6 months after treatment start was an increase of 12.2/cm(2) in dutasteride group and 4.7/cm(2) in placebo group and this difference was statistically significant (P =.0319). Dutasteride showed significantly higher efficacy than placebo group by subject self-assessment and by investigator and panel photographic assessment. There was no major difference in adverse events between two groups. LIMITATIONS: The study was limited to 6 months. CONCLUSIONS: This study clearly showed that 0.5 mg of dutasteride improved hair growth and was relatively well tolerated for the treatment of male pattern hair loss.

7 The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study. Combination therapy with dutasteride and tamsulosin provides significantly greater benefit than either monotherapy for various patient-reported outcomes in men with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and prostatic enlargement. To investigate whether combination therapy is more effective than either monotherapy in reducing the relative risk for acute urinary retention (AUR), BPH-related surgery, and BPH clinical progression over 4 yr in men at increased risk of progression. The Combination of Avodart and Tamsulosin (CombAT) study was a 4-yr, multicenter, randomised, double-blind, parallel-group study in 4844 men 50 yr of age with a clinical diagnosis of BPH, International Prostate Symptom Score 12, prostate volume 30 cm3, prostate-specific antigen ng/ml, and maximum urinary flow rate (Qmax) >5 and 15 ml/s with minimum voided volume 125 ml. Oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. The 4-yr primary end point was time to first AUR or BPH-related surgery. Secondary end points included BPH clinical progression, symptoms, Qmax, prostate volume, safety, and tolerability. Combination therapy was significantly superior to tamsulosin monotherapy but not dutasteride monotherapy at reducing the relative risk of AUR or BPH-related surgery. Combination therapy was also significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression. Combination therapy provided significantly greater symptom benefit than either monotherapy at 4 yr. Safety and tolerability of combination therapy was consistent with previous experience with dutasteride and tamsulosin monotherapies, with the exception of an imbalance in the composite term of cardiac failure among the three study arms. The lack of placebo control is a study limitation. The 4-yr CombAT data provide support for the long-term use of dutasteride and tamsulosin combination therapy in men with moderate-to-severe LUTS due to BPH and prostatic enlargement. Alpha-Blocker Therapy Can Be Withdrawn in the Majority of Men Following Initial Combination Therapy with the Dual 5α-Reductase Inhibitor Dutasteride. The Symptom Management After Reducing Therapy (SMART-1) study examined the combination of the dual action 5αreductase inhibitor (5ARI) dutasteride, and α1-blocker tamsulosin, followed by withdrawal of tamsulosin in men with symptomatic BPH. 327 BPH patients were randomised to 0.5 mg dutasteride and 0.4 mg tamsulosin for 36 weeks (DT36) or 0.5 mg dutasteride and 0.4 mg tamsulosin for 24 weeks followed by dutasteride and tamsulosin matched placebo for the remaining 12 weeks (DT24+D12). Patients assessment of their symptoms, IPSS at weeks 24, 30, and drug safety were evaluated. 77% of DT24+D12 patients felt the same/better at week 30 compared with week 24 (changes in IPSS were consistent with this finding). Of those subjects with an IPSS <20 who changed to dutasteride monotherapy at week 24, 84% switched without a noticeable deterioration in their symptoms. In the 27% of men with severe baseline symptoms (IPSS 20) who had withdrawal of tamsulosin therapy at week 24, 42.5% reported a worsening of their symptoms compared with 14% in the DT36 group. The regimens were well tolerated. Dutasteride can be used in a 24-week combination with tamsulosin, to achieve rapid onset of symptom relief in patients at risk of underlying disease progression. This symptom relief is maintained in the majority of patients after the α1-blocker is removed from the combination. Patients with severe symptoms may benefit from longer-term combination therapy.

8 REFERÊNCIAS ARENA, F. Specific antigen prostatic changes during treatment with finasteride or dutasteride for benign prostatic hyperplasia. Minerva Urol. Nefrol. v. 65, n. 3, p Disponível em:< Acesso em: 21/06/2016, às 17:15. BARKIN, J. et al. Alpha-Blocker Therapy Can Be Withdrawn in the Majority of Men Following Initial Combination Therapy with the Dual 5α- Reductase Inhibitor Dutasteride. European Urology. v. 44, n. 4, p Disponível em:< Acesso em: 21/06/2016, às 17:41. BOERSMA, I. H. et al. The effectiveness of finasteride and dutasteride used for 3 years in women with androgenetic alopecia. Indian J Dermatol Venereol Leprol. v. 80, n. 6, p Disponível em:< Acesso em: 29/06/2016, às 14:29. BOYAPATI, A.; SINCLAIR, R. Combination therapy with finasteride and low-dose dutasteride in the treatment of androgenetic alopecia. Australasian Journal of Dermatology. v. 54, n. 1, p Disponível em:< Acesso em: 29/06/2016, às 15:29. CRANWELL, W. C.; SINCLAIR, R. Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hair transplantation. Australasian Journal of Dermatology. doi: /ajd Disponível em:< Acesso em: 29/06/2016, às 14:23. EUN, H. C. et al. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: a randomized, double-blind, placebo-controlled, phase III study. American Academy of Dermatology. v. 63, n. 2, p Disponível em:< Acesso em: 29/06/2016, às 15:40. GUPTA, A. K.; CHARRETTE, A. The efficacy and safety of 5α-reductase inhibitors in androgenetic alopecia: a network meta-analysis and benefitrisk assessment of finasteride and dutasteride. J Dermatolog Treat. v. 25, n. 2, p Disponível em:< Acesso em: 29/06/2016, às 15:23. HARCHA, W. G. et al. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. American Academy of Dermatology. v. 70, n. 3, p Disponível em:< Acesso em: 29/06/2016, às 15:13. JUNG, J. Y. et al. Effect of dutasteride 0.5 mg/d in men with androgenetic alopecia recalcitrant to finasteride. The International Society of Dermatology. v. 53, n. 11, p Disponível em:< Acesso em: 29/06/2016, às 15:00. LACY F.C.; ARMSTRONG L.L.; GOLDMAN M.P.; LANCE L.L. Drug Information Handbook. American Pharmacists Association. Lexi-Comp. 23ª edição, RAFI, A. W.; KATZ, R. M. Pilot Study of 15 Patients Receiving a New Treatment Regimen for Androgenic Alopecia: The Effects of Atopy on AGA. ISRN Dermatol. doi: /2011/ Disponível em:< Acesso em: 30/06/2016, às 14:44. ROEHRBORN, C. G. et al. The Effects of Combination Therapy with Dutasteride and Tamsulosin on Clinical Outcomes in Men with Symptomatic Benign Prostatic Hyperplasia: 4-Year Results from the CombAT Study. European Urology. v. 57, n. 1, p Disponível em:< Acesso em: 21/06/2016, às 17:29. TSUNEMI, Y. et al. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. The Journal of Dermatology. doi: / Disponível em:< Acesso em: 29/06/2016, às 14:15. YIM, E. et al. 5α-Reductase inhibitors in androgenetic alopecia. Curr Opin Endocrinol Diabetes Obes. v. 21, n. 6, p Disponível em:< Acesso em: 29/06/2016, às 14:36.