Long-term prothionamide compliance: A study carried out in India using a combined formulation containing prothionamide, dapsone and isoniazid

Abstract

A comprehensive study of the self-administration of prothionamide is described in which over 2000 urine samples wee collected from some 60 South Indian patients over a 2-year period. Prothionamide (350 mg) was prescribed for daily self-administration as the commercially available combined formulation 'Isoprodian' that also contains dapsone and isoniazid. Drug ingestion was monitored by testing the samples qualitatively and quantitatively for the presence of the isoniazid metabolites acetylisoniazid and isonicotinic acid, and for dapsone together with its diazotisable metabolites. About a third of the patients suffered from moderate or severe gastrointestinal side-effects attributed to prothionamide but no hepatic toxicity was encountered, whether or not treatment was supplemented with monthly supervised doses of rifampicin. The results obtained using the different urine-test methods correlated well and it was concluded that overall just over half the prescribed doses had been ingested. Although enormous variations in individual patient compliance were demonstrated, there was a continuous spectrum of drug taking and patients could not be simply grouped into good or poor compliers. Older patients took their prescribed treatment less regularly. The compliance of patients who suffered from severe gastrointestinal side-effects was markedly impaired and improved when daily thioamide treatment was replaced by dapsone. The proportion of positive urine tests among samples collected at the patients' monthly clinic visits was similar to those collected by means of surprise home visits. It was concluded that if prothionamide is used as an alternative to clofazimine in the multidrug treatment of lepromatous leprosy its compliance should be monitored using an isoniazid-marked formulation.