RESUMO
In 1982-1984 we conducted a six-month clinical trial in 50 previously untreated lepromatous leprosy patients randomly assigned to directly observed monotherapy with one of two thioamides, ethionamide or prothionamide, each given six times a week at doses of either 250 mg or 500 mg. The findings of this study have only recently been analyzed, and the potential for the use of these thioamides in leprosy patients placed in perspective. However, because of the small number of patients included in this study, the results must be interpreted with some caution. Clinical improvement was noted in 74% of the patients treated with ethionamide and in 83% of those treated with prothionamide. Therapy was well tolerated and drug-related hepatotoxicity did not require discontinuation of therapy. The 500-mg dose of both ethionamide and prothionamide resulted in loss in Mycobacterium leprae viability more rapidly than did the 250-mg dose, and prothionamide at both dose levels was superior to the equivalent dose of ethionamide. Overall killing of M. leprae in this study was found to be similar to that obtained previously with dapsone and clofazimine, but less than was obtained with rifampin, minocycline, clarithromycin, pefloxacin, and ofloxacin.
Assuntos
Etionamida/uso terapêutico , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Mycobacterium leprae/crescimento & desenvolvimento , Protionamida/uso terapêutico , Adolescente , Adulto , Animais , Biópsia , Criança , Relação Dose-Resposta a Droga , Etionamida/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Masculino , Camundongos , Pessoa de Meia-Idade , Protionamida/efeitos adversosAssuntos
Dapsona/efeitos adversos , Isoniazida/efeitos adversos , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Protionamida/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde da População RuralRESUMO
In order to assess the potential additive liver toxicity of isoniazid to that of a thioamide-containing treatment, a prospective, randomized, double-blind trial of 24 weeks' duration involving 772 adult patients was conducted in four leprosy centers--two in India, one in Madagascar, and one in the Ivory Coast. Patients with multibacillary leprosy were given daily 100 mg dapsone (DDS) and 350 mg prothionamide (PTH) plus monthly 600 mg rifampin (RMP) in combination either with 350 mg isoniazid (INH) or with a placebo. After clinical and laboratory (including HBs-Ag testing) examinations on admission, the side effects (especially gastrointestinal disturbances and liver toxicity) were assessed at regular intervals during treatment by laboratory testing (aminotransferases, bilirubin, alkaline phosphatase) and by recording spontaneous complaints. Analysis of the frequency and seriousness of the side effects was made before breaking the code (with or without INH). Although 10% of the patients had liver toxicity leading to stopping treatment, no significant difference in the occurrence of side effects was observed between patients treated with or without INH. Most (75%) of the observed side effects occurred during the first 4 weeks of treatment, and the time of their onset was not related to INH. Body weight and age were factors related to the frequency of side effects [the higher the body weight, the lesser the rate of side effects (p = 0.03)] and the rate of serious side effects increased with age (p = 0.02). But, again, the frequency of the side effects was not related to INH administration. Therefore, from the present study it can be concluded that INH does not increase the toxicity of the thioamide-containing treatment.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Dapsona/efeitos adversos , Isoniazida/efeitos adversos , Hansenostáticos/efeitos adversos , Hanseníase Virchowiana/tratamento farmacológico , Protionamida/efeitos adversos , Adolescente , Adulto , Dapsona/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Incidência , Isoniazida/administração & dosagem , Hansenostáticos/uso terapêutico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Protionamida/administração & dosagem , Rifampina/administração & dosagemAssuntos
Dapsona/administração & dosagem , Isoniazida/administração & dosagem , Ácidos Isonicotínicos/administração & dosagem , Cooperação do Paciente , Protionamida/administração & dosagem , Adolescente , Adulto , Dapsona/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Índia , Isoniazida/efeitos adversos , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Virchowiana/urina , Hanseníase Tuberculoide/tratamento farmacológico , Hanseníase Tuberculoide/urina , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Protionamida/efeitos adversos , Fatores de TempoAssuntos
Dapsona/administração & dosagem , Isoniazida/administração & dosagem , Ácidos Isonicotínicos/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Protionamida/administração & dosagem , Rifampina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Dapsona/efeitos adversos , Dapsona/uso terapêutico , Combinação de Medicamentos/administração & dosagem , Combinação de Medicamentos/efeitos adversos , Combinação de Medicamentos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Protionamida/efeitos adversos , Protionamida/uso terapêutico , Rifampina/efeitos adversos , Rifampina/uso terapêuticoAssuntos
Dapsona/administração & dosagem , Isoniazida/administração & dosagem , Ácidos Isonicotínicos/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Protionamida/administração & dosagem , Rifampina/administração & dosagem , Dapsona/efeitos adversos , Dapsona/uso terapêutico , Combinação de Medicamentos/administração & dosagem , Combinação de Medicamentos/efeitos adversos , Combinação de Medicamentos/uso terapêutico , Quimioterapia Combinada , Estudos de Avaliação como Assunto , Seguimentos , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Hansenostáticos/uso terapêutico , Malta , Protionamida/efeitos adversos , Protionamida/uso terapêutico , Recidiva , Rifampina/efeitos adversos , Rifampina/uso terapêuticoAssuntos
Dapsona/administração & dosagem , Isoniazida/administração & dosagem , Ácidos Isonicotínicos/administração & dosagem , Hansenostáticos/administração & dosagem , Hanseníase/tratamento farmacológico , Protionamida/administração & dosagem , Rifampina/administração & dosagem , Dapsona/efeitos adversos , Dapsona/uso terapêutico , Combinação de Medicamentos/administração & dosagem , Combinação de Medicamentos/efeitos adversos , Combinação de Medicamentos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Masculino , Protionamida/efeitos adversos , Protionamida/uso terapêutico , Rifampina/efeitos adversos , Rifampina/uso terapêutico , TanzâniaRESUMO
Because a 13% incidence of hepatotoxicity was observed in a first study of multibacillary leprosy patients treated daily with dapsone, rifampin, and 10 mg/kg thioamide, the patients were treated in a second study with 5 mg/kg thioamide in daily combination with dapsone and rifampin. In this study, monthly assessments of liver function were performed in order to detect early hepatic disturbances. Despite the reduced dosage of thioamide, a 16.5% incidence of hepatotoxicity was observed among 110 multibacillary patients. However, jaundice was observed in only 2 out of 18 cases of hepatotoxicity (11%); whereas it was observed in 5 out of the 7 cases of hepatotoxicity (71%) in the first study (p less than 0.05). The decrease in the thioamide dosage and the performance of monthly assessments of liver function did not decrease the incidence of hepatotoxicity but did decrease its severity. It is concluded that thioamide should not be used in daily combination with rifampin unless the daily dose is 5 mg/kg and monthly assessments of liver function are routinely performed.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácidos Isonicotínicos/efeitos adversos , Hanseníase/tratamento farmacológico , Protionamida/efeitos adversos , Rifampina/efeitos adversos , Adolescente , Adulto , Idoso , Peso Corporal , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Hanseníase/fisiopatologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Protionamida/administração & dosagem , Rifampina/administração & dosagemRESUMO
Hepatotoxicity in two drug regimens was studied at Central Leprosy Teaching and Research Institute, Chengalpattu (Tamil Nadu) during 1983-84. In 'P' regimen-prothionamide 350 mg daily, dapsone 100 mg daily and rifampicin 600 mg at monthly intervals were given. In' C' regimen-dapsone 100 mg daily, rifampicin 600 mg once a month and clofazimine 300 mg once a month and 100 mg alternate day were given. Trial was started with fifty multibacillary adult leprosy patients in each group. Enzymatic hepatic dysfunction was noted in 52-58 per cent of the cases even before the therapy was started. In 'P' regimen, four cases of clinical jaundice and six cases of high bilirubinaemia was noticed during the trial as against two cases each of clinical jaundice and high bilirubinaemia in 'C regimen. Of the two cases of clinical jaundice in 'C' regimen, one turned out to be a case of HBV infection. The study which is in progress, indicated higher hepatotoxicity in 'P' regimen which is probably explained by the simultaneous use of two hepatotoxic drugs. Viral hepatitis is endemic in this area and might have aggravated the hepatotoxicity observed.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácidos Isonicotínicos/efeitos adversos , Hanseníase/tratamento farmacológico , Protionamida/efeitos adversos , Adolescente , Adulto , Dapsona/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Icterícia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Rifampina/efeitos adversosRESUMO
Combined therapy with prothionamide and dapsone was instituted in fifteen active untreated lepromatous leprosy cases for a period of 18 months. Clinical improvement was good with attainment of zero morphological index in about 66% cases. Bacteriological improvement was rather unsatisfactory as one case only reached zero level. Side effects were observed in few cases necessitating withdrawal of combined therapy and patients' prothionamide compliance was rather unimpressive.
Assuntos
Dapsona/administração & dosagem , Ácidos Isonicotínicos/administração & dosagem , Hanseníase/tratamento farmacológico , Protionamida/administração & dosagem , Adulto , Quimioterapia Combinada , Humanos , Hanseníase/microbiologia , Hanseníase/patologia , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Protionamida/efeitos adversosAssuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácidos Isonicotínicos/efeitos adversos , Hanseníase/tratamento farmacológico , Protionamida/efeitos adversos , Rifampina/efeitos adversos , Adulto , Idoso , China , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protionamida/uso terapêutico , Rifampina/uso terapêuticoRESUMO
Two groups of patients were chosen for this treatment; the first group of 14 patients was treated with a daily dose of 600 mg. of Rifampicine and the second group with Rifampicine associated with Isoprodian (1-2 tablets). In the first group clinical and bacteriological improvement was apparent. This was parallel in bacteriological and morphological index. Two patients became negative in nasal mucous. Tolerance was good and number of leprosy reactions 65%. In the second group clinical improvement was good in general but one case that presented a continuous polyneuritis and hepatic intolerance. Bacteriological results were lightly lower than the first group and the number of leprosy reactions 85%. This treatment is considered inferior to the sulfons, which is very expensive. A longer period of time will be needed to appriase results.