Safety and Efficacy of Thioridazine as Salvage Therapy in Indian Patients with XDR-TB

Zarir      F. Udwadia; Tiyas      Sen; Lancelot      M. Pinto

Abstract

New drugs are desperately needed to combat XDR-TB as effective treatment involves at least four drugs to which the patient is sensitive or has never received in the past. Most Indian patients have received almost all second line drugs and have amplified resistance to most of the available drugs. Thioridazine has proven anti tuberculous effects in vitro and in vivo mouse models and we used this drug as salvage therapy in 4 Indian patients with XDR (near total drug resistance) with advanced disease. We found this drug to be well tolerated, even in this malnourished and ill patient population. It also resulted in clinical improvement in 3 of the 4 patients. Larger studies are being planned with this drug being added on to standardized or individualized XDR-TB regimens at an earlier stage. Because thioridazine has been used successfully for therapy of XDR-TB when in combination with antibiotics to which the patients were nonresponsive, the suggestion has been made that Thioridazine is eligible for patent as “New Use”.

Keywords: Thioridazine, salvage drug, XDR-TB, QT-interval, TB Strains, sputum conversion, central inflammatory response, antituberculous effects, drug resistant tuberculosis, thioridazine therapy