Rifamycins and Cardiovascular Agents: Drug Drug Interactions

General Tuberculosis (TB) Therapy Information
Many cardiovascular agents are metabolized via the Cytochrome P450 (CYP450) enzymatic system in the liver . Rifampin is a potent inducer of the Cytochrome P450 and accounts for many of the drug
interactions that occur during TB therapy.
Rifabutin is a weaker inducer of the Cytochrome P450 system, potentially interacting with some of the same medications as Rifampin.
Rifapentine is also a potent inducer of CYP450 enzymatic system in the liver with drug-drug interactions of a severity similar to those of rifampin.

Angiotensin Converting Enzyme (ACE) Inhibitors

Generic
(Class Effect)

Clinical Effect
Decreased blood pressure

Interactions
Rifamycin: ?ACE Inhibitor levels ~30% (poor evidence, no studies)

Recommendations
Increase blood pressure monitoring; Consider ACE Inhibitor dose adjustment.

Angiotensin Receptor Blockers (ARBs)

Generic
(Class Effect)

Clinical Effect
Decreased blood pressure. renoprotective.

Interactions
Rifamycin: ?Angiotensin II Receptor Blockers levels ~35%
(poor evidence, no studies)

Recommendations
Increase blood pressure monitoring; Consider Angiotensin II Receptor Blockers dose adjustment.

Beta Blockers

Generic
metoprolol

Clinical Effect
decreased blood pressure

Interactions
Rifamycin: ?metoprolol levels 33%

Recommendations
Increase blood pressure monitoring; Consider dose adjustment.

Generic
propranolol

Clinical Effect
?blood pressure

Interactions
Rifamycin: doubled apparent oral clearance

Recommendations
Increase blood pressure monitoring; Consider dose adjustment.

Generic
bisoprolol

Clinical Effect
?blood pressure

Interactions
Rifamycin: ?bisoprolol levels 34%

Recommendations
Increase blood pressure monitoring; Consider dose adjustment.

Calcium Channel Blockers (CCBs)

Generic
nifedipine

Clinical Effect
?blood pressure

Interactions
Rifamycin: ?nifedipine levels 92-97% (Contraindicated*)

Recommendations
Increase blood pressure monitoring; Consider dose adjustment; Consider switching to other antihypertensive agents with
less interaction. *Major interactions occurr between orally administered nifedipine and rifampin. IV
administration significantly reduces the potency of the interactions.

Generic
amlodipine

Clinical Effect
?blood pressure

Interactions
Rifamycin: theoretically ? amlodipine levels

Recommendations
Increase blood pressure monitoring; Consider dose adjustment; Consider switching to other antihypertensive agents with
less interaction.

Generic
diltiazem

Clinical Effect
?blood pressure

Interactions
Rifamycin: ?diltiazem levels

Recommendations
Increase blood pressure monitoring; Consider dose adjustment; Consider switching to other antihypertensive agents with
less interaction.

Generic
verapamil

Clinical Effect
?blood pressure

Interactions
Rifamycin: ?verapamil levels 93-99%

Recommendations
Increase blood pressure monitoring; Consider dose adjustment; Consider switching to other antihypertensive agents with
less interaction.

Thiazide Diuretics

Generic
(Class Effect)

Clinical Effect
?blood pressure

Interactions
none noted

Recommendations
no contraindications

HMG CoA Inhibitors (Statins)

Generic
atorvastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin: ?atorvastatin levels 80%

Recommendations
Increase blood pressure monitoring; Consider alternate lipid lowering agent to minimize effect; Consider increasing Statin
dose; Consider using Rifabutin in place of Rifampin.

Generic
rosuvastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin: may ?rosuvastatin levels

Recommendations
Increase blood pressure monitoring; Consider increasing Statin dose; Consider using Rifabutin in place of Rifampin.

Generic
simvastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin: ?simvastatin levels 82-97%

Recommendations
Increase blood pressure monitoring; Consider alternate lipid lowering agent to minimize effect; Consider increasing Statin
dose; Consider using Rifabutin in place of Rifampin.

Generic
pravastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin: theoretically ?statin levels

Recommendations
Increase blood pressure monitoring; Consider alternate lipid lowering agent to minimize effect; Consider increasing Statin
dose; Consider using Rifabutin in place of Rifampin.

Generic
lovastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin: theoretically ?statin levels

Recommendations
Increase blood pressure monitoring; Consider alternate lipid lowering agent to minimize effect; Consider increasing Statin
dose; Consider using Rifabutin in place of Rifampin.

Generic
fluvastatin

Clinical Effect
?cholesterol levels, ?stroke, cardioprotective.

Interactions
Rifamycin:?statin levels ~50%

Recommendations
Increase blood pressure monitoring; Consider alternate lipid lowering agent to minimize effect; Consider increasing Statin
dose; Consider using Rifabutin in place of Rifampin.

Ionotropic/Chronotropic Agents

Generic
digoxin

Clinical Effect
?cardiac output, heart rate control with atrial arrhythmias.

Interactions
Rifamycin: ?levels ~30%

Recommendations
Measure digoxin levels prior to rifampin therapy and then intermittently thereafter. Increase digoxin dose as
necessry to maintain therapeutic levels.

Antiplatelet Agents

Generic
clopidogrel

Clinical Effect
?platelet adhesion

Interactions
?metabolism of clopidogril to active metabolite

Recommendations
Monitor for increased antiplatelet effects such as bruising or bleeding.

References

Micromedex® Healthcare Series. n.d. Thomson Healthcare, Greenwood Village, CO. April 1, 2011 <http://www.thomsonhc.com>.
Niemi M, Backman JT, et al. Pharmacokinetic Interactions with Rifampicin. Clin Pharmacokinet. 2003; 42(9):819-850.

Saima S, Furuie K, et al. The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects. J Clin Pharm. 2002 Feb;53(2):203-6.
Glaser H, Drescher S, et al. Influence of rifampicin on the expression and function of human intestinal cytochrome P450 enzymes.
Herman RJ, Nakamura K, Wilkinson GR, et al: Induction of propranolol metabolism by rifampicin. Br J Clin Pharmacol 1983;;16:565-569.
Bennet P N, John V A, et al. Effect of Rifampicin on Metropolol and Antipyrine . Br. J. clin. Pharmac. (1982), 13, 387-391 Kinetics.
Bhatnagar V, Garcia E P, et al. CYP3A4 and CYP3A5 Polymorphisms and Blood. Am J Nephrol 2010;31:95–103. Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease.

Holtbecker N, Martin F, et al. The Nifedipine-Rifampin Interaction . Drug Metab Dispos. 1996 Oct;24(10):1121-3.

Kolars JC, Schmiedlin-Ren P, Schuetz JD, et al. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992; 90:1871–1878
Strayhorn V A, Baciewicz A M, et al. Update on Rifampin Drug Interactions, III. Arch Intern Med. 1997;157(21):2453-2458.