Protionamide Rifampicin

When thionamides are used in combination with rifam-picin, hepatotoxicity is more common and severe (18,19). There was a 13% incidence of hepatotoxicity in patients with multibaciUary leprosy treated with dap-sone, rifampicin, and protionamide 10 mg/kg/day, and a 17% incidence in 110 patients treated with dapsone, rifampicin, and protionamide 5 mg/kg/day however, although the lower dose of protionamide did not reduce the incidence of hepatotoxicity, it did reduce its severity (20). Protionamide does not affect the pharmacokinetics of rifampicin (21). 

Hepatotoxicity of combined therapy for leprosy has been reported in 39 patients treated with dapsone, pro-tionamide, and rifampicin. There were similar findings in 50 patients treated with dapsone, clofazimine, rifampicin, and protionamide. Deaths probably related to the drngs occurred in both groups after 3-4 months of treatment... 

The drug responsible for liver injury may have been protionamide, although rifampicin administered simultaneously could also have contributed (53). 

Antimycobacterials and related drugs Aminosalicylic acid (PAS), Capreomycin, Clofazimine, Cycloserine, Dapsone, Ethambutol, Ethionamide, Isoniazid, Methaniazide, Protionamide, Pyrazinamide, Rifabutin, Rifampicin (Rifampin), Rifamycin, Rihipentine, Rihiximin... 

Protionamide appears to be very hepatotoxic and this is possibly increased by the concurrent use of rifampicin or rifandin. Pro-... 

Jaundice, liver damage and deaths have occurred in other leprosy patients given rifampicin and protionamide or ethionamide. Protionamide does not affect the pharmacokinetics of either dapsone or rifampicin. ... 

Although not certain, it seems probable that the liver damage was primarily caused by the protionamide, and possibly exacerbated by the rifampicin or the rifandin. 

This serious and potentially life-threatening hepatotoxic reaction to protionamide is established, but the part played by the other drugs, particularly the rifampicin, is uncertain. Strictly speaking this may not be an interaction, bf protionamide is given the liver function should be very closely monitored in order to detect toxicity as soon as possible. 

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