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DRUG INTERACTIONS

Effect of Clarithromycin on Steady-State Digoxin Concentrations

Staff Pharmacist, Department of Pharmacy, National Cardiovascular Center, Osaka, Japan

Kana Matsumoto, MS

Staff Pharmacist, Department of Pharmacy, Kyoritsu Hospital, Hyogo, Japan

Kazuyuki Ueno, PhD

Chief Pharmacist, Department of Pharmacy, National Cardiovascular Center

Mayumi Kodama, BS

Staff of Laboratory, Clinical Laboratory, National Cardiovascular Center

Kohji Yoneda, PhD

Chief of Laboratory, Clinical Laboratory, National Cardiovascular Center

Yoshiaki Katayama, PhD

Head of Laboratory, Clinical Laboratory, National Cardiovascular Center

Kunio Miyatake, MD PhD

Vice-President, Cardiovascular Internal Medicine, National Cardiovascular Center

Reprints: Kazuyuki Ueno PhD, Department of Pharmacy, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita-City, Osaka, 565-8565, Japan, FAX 81-6-6872-8074, E-mail uenok{at}hsp.ncvc.go.jp

OBJECTIVE: To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors.

METHODS: Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin.

RESULTS: Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 ± 0.329 ng/mL; after, 1.36 ± 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration.

CONCLUSIONS: Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.

Key Words: clarithromycin, digoxin, P-glycoprotein

Published Online, December 30, 2002. www.theannals.com, DOI

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