Dificid (Fidaxomicin) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Fidaxomicin and its main metabolite, OP-1118, are substrates of the efflux transporter, P-glycoprotein (P-gp), which is expressed in the gastrointestinal tract.

Cyclosporine

Cyclosporine is an inhibitor of multiple transporters, including P-gp. When cyclosporine was co-administered with DIFICID, plasma concentrations of fidaxomicin and OP-1118 were significantly increased but remained in the ng/mL range [see Clinical Pharmacology]. Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated patients in controlled clinical trials. Based on these results, fidaxomicin may be co-administered with P-gp inhibitors and no dose adjustment is recommended.

OVERDOSAGE

No cases of acute overdose have been reported in humans. No drug-related adverse effects were seen in dogs dosed with fidaxomicin tablets at 9600 mg/day (over 100 times the human dose, scaled by weight) for 3 months.

CONTRAINDICATIONS

Hypersensitivity to fidaxomicin.

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - 7^th edition. CLSI document M11-A7. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087-1898, 2007.