[The need for new antituberculosis agents in Japan]

We discussed the need of new antituberculosis agents in Japan concerning drug adverse reactions in particular as well as drug interactions and drug resistance. We reviewed medical charts of hospitalized patients receiving standard antituberculosis chemotherapy (INH + RFP + EB/SM +/- PZA), and analyzed all symptoms, signs and abnormal laboratory data presumably caused by the chemotherapy. About 48% of 228 cases analyzed had at least 1 episode of adverse reactions: 77 episodes of hepatotoxicity, 15 episodes of ototoxicity, 14 episodes of eruption, 14 episodes of ocular toxicity and so on. About 23% cases treated with RFP, 20% cases with SM, 12% cases with INH and 7.7% cases with EB had at least 1 episode of adverse reactions due to the corresponding agent. In 59 cases, at least one agent was stopped to administer because of adverse reactions. Finally, standard chemotherapy could not be completed in 23% of all cases, and in stead, the other agents, mainly new quinolones, were administered. RFP induces cytochrome P450 3A in the liver to decrease the activities of many drugs, such as cyclosporin A, tacrolimus, protease inhibitor, itraconazole, and clarithromycin. In some clinical settings, RFP cannot be administered in combination with such drugs. In conclusions, new antituberculosis agents that have strong activities with less adverse reactions and drug interactions are needed in Japan, even without considering drug resistance.