Update on Rifampin and Rifabutin Drug Interactions

Rifampin is associated with numerousclinically significantdrug interactions.^1-4 New interactionswith rifampin--aswell as rifabutin--continue tobe reported in studies and clinical observations.Here we present highlightsof our recent update on the interactionsthat are most relevant toprimary care practice.⁵RIFAMPINRifampin is a potent inducer ofboth the hepatic and intestinal cytochromeP-450 (CYP) enzyme systemand the P-glycoprotein (P-gp) transportsystem. Rifampin intracellularconcentrations--and thus the extentto which rifampin is able to induceCYP3A--are strongly correlated withP-gp levels. P-gp is a transmembraneprotein that is a member of the adenosinetriphosphate-binding cassettefamily, a group of molecules that controlconcentrations of both endogenousand exogenous substancesacross cell membranes by functioningas cellular efflux pumps. P-gp isfound at many sites throughout thebody that are essential to drugbioavailability and distribution, suchas the intestinal lumen, the liver, thekidney, and the blood-brain barrier.⁶Why do primary care cliniciansneed to be aware of interactions withrifampin? Although it is primarily indicatedfor tuberculosis (TB), rifampinis also used for other infections (eg,as adjunctive antistaphylococcal therapy).In addition, even though health department physicians usually treatTB--and manage any resultant druginteractions--primary care cliniciansmay add new drugs for concurrentmedical problems during the courseof rifampin therapy.Table 1 shows some examples of well-documented rifampin interactionsthat have major clinical relevance.Noteworthy consequencesinclude:

• Unplanned pregnancy resultingfrom the effect of rifampin on oralcontraceptives.
• Loss of transplanted organs attributableto the interaction of rifampinwith cyclosporine.

Other potentially important interactionsare listed in

Table 2

.More recentlyreported rifampin interactionsare summarized in

Table 3

.

RIFABUTIN

Rifabutin is used with increasingfrequency in patients with HIV infectionor AIDS, and new drug interactionswith this agent continue to bereported. Although rifabutin interactionsare usually less dramatic than rifampininteractions, many are clinicallysignificant.

Table 4

compares rifabutinand rifampin interactions withantiretroviral therapy.

A FINAL CAVEAT

When you prescribe rifampinor rifabutin, it is essential to screenfor drug interactions. To avoid reducedtherapeutic response, therapeuticfailure, or toxic reactionswhen these agents--particularly rifampin--are added to or discontinuedfrom medication regimens, bealert for interactions and managethem appropriately.

References:

REFERENCES:

1.

Baciewicz AM, Self TH. Rifampin drug interactions.

Arch Intern Med

. 1984;144:1667-1671.

2.

Baciewicz AM, Self TH, Bekemeyer WB. Updateon rifampin drug interactions.

Arch Intern Med

.1987;147:565-568.

3.

Borcherding SM, Baciewicz AM, Self TH. Updateon rifampin drug interactions II.

Arch Intern Med

.1992;152:711-716.

4.

Strayhorn VA, Baciewicz AM, Self TH. Update onrifampin drug interactions III.

Arch Intern Med

.1997;157:2453-2458.

5.

Finch CK, Chrisman CR, Baciewicz AM, Self TH.Rifampin and rifabutin drug interactions: an update.

Arch Intern Med

. 2002;162:985-992.

6.

Schuetz EG, Schinkel AH, Relling MV, Schuetz JD.P-glycoprotein: a major determinant of rifampicininducibleexpression of cytochrome P4503A inmice and humans.

Proc Natl Acad Sci U S A

. 1996;93:4001-4005.

7.

Panel on Clinical Practices for Treatment of HIVInfection.

Guidelines for the Use of AntiretroviralAgents in HIV-Infected Adults and Adolescents

. Washington,DC, and San Francisco: Dept of Health andHuman Services and the Henry J. Kaiser FamilyFoundation; April 23, 2001.