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Rifampin Drug Interactions

Mack R. Holdiness, MD, PhD
Arch Intern Med. 1987;147(10):1856. doi:10.1001/archinte.1987.00370100170039.
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To the Editor.  —In their recent article, Baciewicz et al1 presented an excellent update on rifampin drug interactions. There are, however, two therapeutic agents (ethionamide and protionamide) not mentioned that may have serious to potentially fatal consequences when used with rifampin. Ethionamide (α-ethylthioisonicotinamide) is a derivative of isonicotinic acid, and protionamide is the N-propyl derivative of ethionamide. These thioamides are used as "second-line" antituberculosis agents and are also used for the treatment of leprosy.It has been previously observed that simultaneous administration of rifampin and protionamide did not result in alteration of the pharmacokinetic properties of these antibiotics.2 Regardless, clinically important interactions have been documented. Pattyn et al3 noted hepatitis, mostly with jaundice, in 4.5% of 596 multibacillary leprosy patients treated daily for six months with a regimen of rifampin (600 mg), ethionamide (500 mg), and dapsone (100 mg). Mortality from this subgroup of individuals with


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