Fixed-dose combination drugs for tuberculosis: application in standardised treatment regimens

Short-course chemotherapy is highly efficacious in treating tuberculosis (TB). However, the length (>/=6 months) and complexity (three or four different drugs) of the treatment makes adherence difficult. Erratic treatment not only fails to cure patients but also creates chronically contagious cases, who may excrete drug-resistant TB bacteria. The Directly Observed Treatment Short-course (DOTS) strategy recommended by WHO provides a comprehensive organisational and infrastructural framework for the rational use of diagnosis, drug supply, as well as case and programme management services, in TB control. WHO and other organisations recommend fixed-dose combination formulations (FDCs) as a further step to facilitate the optimal drug treatment of TB. Using FDCs in TB control will simplify the doctor's prescription and patient's drug intake, as well as the drug supply management of the programme. By preventing monotherapy and facilitating the ingestion of adequate doses of the constituent anti-TB drugs, FDCs are expected to help prevent the emergence of drug resistance. This article presents the international recommendations for the use of FDCs in TB programmes. The fundamental issue is to obtain drug supplies of good quality. A laboratory network for quality testing, including bioavailability testing of FDCs exists, and the recently established Global TB Drug Facility (GDF) supplies quality TB drugs, including 4-drug FDCs, to countries requesting assistance. This articles deals with the requirements for a successful transition to FDC-based treatment. It emphasises the need for appropriately revised programme documentation (programme manual, training modules, treatment guidelines and forms), training of staff at all levels, carefully calculated drug needs, and a plan for the exhaustion of existing stocks of loose tablets and the phasing-in of FDCs at all levels of the programme at the same time. Loose drugs for individualised treatment of patients with adverse effects should be kept at district or central health institutions.