Previous isothermal microcalorimetry studies at 40 °C, with and without humidity (RH 75%), had shown no incompatibility between rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol HCl (EMB). The purpose of this study was to explore any interactions at an increased temperature of 50 °C and also to investigate the possibility of incompatibilities between the drugs and tablet excipients used in the most commonly prescribed commercial four-drug TB FDC. No incompatibilities were observed between the excipients, or when the excipients were tested with the four drugs individually. Incompatibility was observed with the four drugs combined.