RESUMO
BACKGROUND & AIMS: Cyproterone acetate (CPA), an anti-androgenic drug for prostate cancer, has been associated with drug-induced liver injury (DILI). We aim to expand the knowledge on the spectrum of phenotypes and outcomes of CPA-induced DILI. METHODS: Twenty-two males (70 ± 8 years; range 54-83) developing liver damage as a result of CPA therapy (dose: 150 ± 50 mg/day; range 50-200) were included. Severity index and causality by RUCAM were assessed. RESULTS: From 1993 to 2013, 22 patients were retrieved. Latency was 163 ± 97 days. Most patients were symptomatic, showing hepatocellular injury (91%) and jaundice. Liver tests at onset were: ALT 18 ± 13 × ULN, ALP 0.7 ± 0.7 × ULN and total serum bilirubin 14 ± 10 mg/dl. International normalized ratio values higher than 1.5 were observed in 14 (66%) patients. Severity was mild in 1 case (4%), moderate in 7 (32%), severe in 11 (50%) and fatal in 3 (14%). Five patients developed ascitis, and four encephalopathy. One patient had a liver injury that resembled autoimmune hepatitis. Eleven (50%) were hospitalized. Nineteen patients recovered after CPA withdrawal, although three required steroid therapy (two of them had high ANA titres). Liver biopsy was performed in seven patients (two hepatocellular collapse, one submassive necrosis, two cholestatic hepatitis, one cirrhosis with iron overload and one autoimmune hepatitis). RUCAM category was 'highly probable' in 19 (86%), 'probable' in 1 (4%), and 'possible' in 2 (9%). CONCLUSIONS: CPA-induced liver injury is severe and can be fatal, and may occasionally resemble autoimmune DILI. The benefit/risk ratio of this drug should be thoroughly assessed in each patient.
Assuntos
Corticosteroides/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas , Acetato de Ciproterona , Fígado/patologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Anti-Inflamatórios/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Acetato de Ciproterona/administração & dosagem , Acetato de Ciproterona/efeitos adversos , Humanos , Icterícia/etiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Medição de Risco , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Drug-induced liver injury (DILI) remains a major problem for drug development and represents a challenging diagnosis for clinicians. The absence of specific biomarkers for diagnosing DILI precludes the availability of reliable data on the epidemiology of the disease. In this study we aimed to describe the features of idiosyncratic hepatotoxicity reports in Latin American countries. MATERIAL AND METHODS: A literature search was performed using the online version of MEDLINE, EMBASE, Scopus, Google Scholar and specific data bases from Latin America (LA) (Scielo, Lilacs) to identify any case report or case series of published DILI from 1996 to 2012. From 1996 to 2012, a total of 176 patients with DILI were published in LA, involving 53 suspicious drugs. The median age in the adult population of these patients was 55 years (17-82) with prevalence of women (67%). Among main therapeutic classes, the rank order was led by non-steroidal anti-inflammatory (61 cases) and systemic antibacterial drugs (37 cases). Nimesulide was the individual drug responsible for the highest number of cases (53), followed by cyproterone acetate (18), nitrofurantoin (17), antituberculous drugs (13) and flutamide (12). Thirty two percent of published cases evolved to acute liver failure (ALF), and half of the subjects required liver transplantation or eventually died. CONCLUSIONS: This study represents the first structured attempt to assess the spectrum of DILI profile in LA. The establishment of a Latin American registry to collect prospective DILI cases using a standardized protocol will advance our knowledge about idiosyncratic DILI in this region.
Assuntos
Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Acetato de Ciproterona/efeitos adversos , Feminino , Flutamida/efeitos adversos , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Sulfonamidas/efeitos adversos , Adulto JovemRESUMO
Cyproterone acetate (CPA) is an oral anti-androgen commonly used to treat advanced prostate cancer. A variety of hepatotoxic reactions has been reported with CPA. Here we describe a case of a male patient who developed severe drug-induced hepatotoxicity during the treatment with CPA. The case, presenting sub-acute hepatitis, was characterized by a rapid evolution of cirrhosis and a protracted activity during the period of a few months despite the treatment withdrawal and an apparent benefits of corticosteroids, suggesting their indication in life threatening cases.
Assuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Acetato de Ciproterona/efeitos adversos , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Idoso , Budesonida/uso terapêutico , Colagogos e Coleréticos/uso terapêutico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
The majority of breast cancers in male patients are hormone receptor positive. Tamoxifen has proven to be successful in both adjuvant and metastatic settings and remains the standard of care. Given the improved outcomes in female patients with aromatase inhibitors (AI), these drugs have become a potential therapeutic tool for male patients. Preliminary data show effective suppression of oestradiol levels in males treated with AI and some reports have demonstrated objective responses. Here we report a case of a male patient with metastatic breast cancer treated with letrozole who achieved clinical response associated with a decrease in blood oestradiol levels.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama Masculina/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Estrogênios , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/uso terapêutico , Progesterona , Triazóis/uso terapêutico , Neoplasias da Mama Masculina/sangue , Neoplasias da Mama Masculina/induzido quimicamente , Neoplasias da Mama Masculina/enzimologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/induzido quimicamente , Carcinoma Ductal de Mama/enzimologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/secundário , Terapia Combinada , Acetato de Ciproterona/efeitos adversos , Acetato de Ciproterona/uso terapêutico , Estradiol/sangue , Estrogênios Conjugados (USP)/efeitos adversos , Estrogênios Conjugados (USP)/uso terapêutico , Humanos , Letrozol , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hormônio-Dependentes/induzido quimicamente , Neoplasias Hormônio-Dependentes/enzimologia , Transtornos Fóbicos/tratamento farmacológico , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/secundário , Testosterona/sangue , Resultado do TratamentoRESUMO
El tratamiento del síndrome climatérico con (terapia combinada secuencial de 21 días; estradiol valerato 2 mg y ciproterona acetato 1 mg) es adecuado para el control de la sintomatología climatérica y para la prevención de osteoporosis postmenopáusica. Este preparado es tan eficaz como el resto de los preparados estrógeno-progestativos conocidos, presentando reacciones adversas similares. Sin embargo, atendiendo al perfil lipídico, tensión arterial y control del ciclo, el empleo de la ciproterona como gestágeno sí conlleva ciertas ventajas. La mayoría de las mujeres en tratamiento experimentan un aumento de las HDL- colesterol y un mantenimiento de las cifras de tensión arterial, habiéndose incluso descrito descensos estadísticamente significativos de la tensión arterial diastólica. Hasta un 87,7 por ciento de las mujeres tratadas experimenta ciclos regulares. Por tanto, este nuevo preparado hormonal puede ser considerado como un tratamiento de elección para mujeres perimenopáusicas y aquellas postmenopáusicas iniciales que acepten volver a tener menstruaciones
Assuntos
Humanos , Feminino , Climatério/efeitos dos fármacos , Acetato de Ciproterona/administração & dosagem , Estradiol/administração & dosagem , Terapia de Reposição Hormonal , Valeratos/administração & dosagem , Acetato de Ciproterona/efeitos adversos , Combinação de Medicamentos , Osteoporose Pós-Menopausa/prevenção & controleRESUMO
OBJECTIVES: To compare the effect on plasma lipids of conjugated estrogens/medroxyprogesterone acetate (CE/MPA) and estradiol valerate/cyproterone acetate (EV/CPA) in healthy peri and postmenopausal women during 1 year. METHODS: Multicentric, controlled, single blinded Phase III clinical trial. Women were randomized to two treatment groups: Group A (n = 49 women): CE 0.625 mg/day for 21 days and MPA 5 mg from day 12 to 21. Group B (n = 55 women): EV 2 mg/day for 21 days and CPA 1 mg from day 12 to 21. Total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C), triglycerides, aminotransferases and alkaline phosphatase were measured before starting therapy, and after 3, 6, 9 and 12 months of hormone replacement therapy (HRT). TC/HDL-C and LDL-C/HDL-C ratios were determined. RESULTS: There were no changes in TC levels. HDL-C increased and LDL-C decreased significantly, with no differences between groups but within each group. Triglycerides increased significantly but remained within normal values, with no differences between groups. TC/HDL-C ratio showed a slight and steady decrease in both groups. LDL-C/HDL-C ratio decreased in both treatment groups. CONCLUSION: Both cyclic sequential preparations used in HRT showed a favorable effect on plasma lipids in healthy peri and postmenopausal women, with an increase in HDL-C and a decrease in LDL-C levels, as well as in the LDL-C/HDL-C and TC/HDL-C ratios. Our study confirms the positive effect of estrogens on lipids, which does not seem to be adversely affected by the addition of progestogens derived from pregnanes.