Rifampin and Rifabutin Drug Interactions

Abstract

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few examples of well-documented clinically significant interactions include interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or digoxin, verapamil hydrochloride, human immunodeficiency virus-related protease inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent reports have demonstrated clinically relevant interactions with numerous other drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin, propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Enhanced knowledge of known interactions will continue to develop, including research on the induction of specific cytochrome P-450 isoenzymes and on the importance of the P-glycoprotein transport system. New rifampin and rifabutin interactions will be discovered with further investigations.

The Effect of P-Glycoprotein Inhibition and Activation on the Absorption and Serum Levels of Cyclosporine and Tacrolimus in Rats

“…Verapamil, which increased the intestinal absorption of cyclosporine and tacrolimus in this study, has previously been reported to be a substrate of P-gp when used in low doses and to strongly inhibit P-gp when used high doses [8]. Furthermore, it has been suggested that rifampicin activates P-gp in vivo and in vitro [11,12]. Although there are some other studies about the effects of P-glycoprotein modulation on the bioavailability of several drugs [16][17][18], to best of the authors' knowledge, this is the first study to investigate the effects of P-gp-inhibiting and -activating drugs on the intestinal absorption of immunosuppressive drugs.…”

“…On the other hand, P-gp can easily be activated by some agents, such as rifampicin [11,12]. P-glycoprotein plays an important role in the intestinal absorption of immunosupressive agents, including cyclosporine and tacrolimus [13][14][15].…”

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

“…Rifabutin, a drug in the same family as rifampicin (rifamycins), is also characterized by inducing the metabolism of certain drugs, although to a lesser degree than rifampicin. (Finch et al, 2002) …”

“…(Blumberg et al, 2003;Finch et al, 2002;Sekar et al, 2010;Spradling et al, 2002) In general, the use of rifampicin (rifabutin is preferred due to their lesser inductive effect than rifabutin) with a single PI, including the most recent, such as amprenavir and atazanavir, is considered contraindicated (level 1: very high risk), because in most cases, rifampicin produces non-efficacy PIs concentrations. Besides, most treatment guidelines for HIV/AIDS patients extend this contraindication even to PIs combined with ritonavir used as a pharmacokinetic extension agent (enhancer).…”

“…(DHSS, 2011) Rifampicin and NNRTI. (Finch et al, 2002;de Jong et al, 2004;Ribera et al, 2001;Ramachandran et al, 2006;Weiner et al, 2005) In general, the use of rifampicin together with delavirdine is considered contraindicated (Borin et al, 1997) (level 1: very high risk).…”