Fidaxomicin: A Novel Macrocyclic Antibiotic for the Treatment of Clostridium difficile Infection

Tonya Crawford, Pharm.D; Emily Huesgen, Pharm.D; Larry Danziger, Pharm.D

Disclosures

Am J Health Syst Pharm. 2012;69(11):933-943. 

In This Article

Drug Interactions

Fidaxomicin and OP-1118 are weak inhibitors of cytochrome P-450 (CYP) enzymes. A drug–drug interaction study to determine potential interactions between CYP substrates and fidaxomicin was conducted.[49] Warfarin, omeprazole, and midazolam served as marker substrate drugs for CYP2C9, CYP2C19, and CYP3A4/5, respectively. The coadministration of fidaxomicin every 12 hours with the CYP substrate mixture composed of warfarin, omeprazole, and midazolam did not result in a significant change in the pharmacokinetics of the marker substrate drugs.

Fidaxomicin is a substrate and inhibitor of P-glycoprotein, and its metabolite, OP-1118, is a substrate for P-glycoprotein. Administration of cyclosporine, a P-glycoprotein inhibitor, given one hour before fidaxomicin administration, resulted in an increase in both the maximum plasma concentration (Cmax) and the area under the plasma concentration–time curve (AUC) of fidaxomicin and its metabolite, OP-1118.[49] The mean Cmax for fidaxomicin increased from 5.20 to 26.9 ng/mL, and the mean Cmax for OP-1118 increased from 12 to 132 ng/mL. The plasma AUC of fidaxomicin and OP-1118 increased 1.9-fold and 4.1-fold, respectively, when cyclosporine was coadministered.[50] To investigate the effect of fidaxomicin on P-glycoprotein substrates, fidaxomicin was administered at least one hour before digoxin, a P-glycoprotein substrate. No clinically meaningful pharmacokinetic interaction was found between fidaxomicin and digoxin.

The dosage of fidaxomicin does not need to be adjusted during concomitant therapy with CYP substrates and P-glycoprotein inhibitors. Precautions and contraindications have not been reported with the use of fidaxomicin.

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