Australia - Several published reports are available of cases in which a macrolide antibiotic has increased blood concentration of digoxin. It is now known that digoxin is transported by P-glycoprotein - perhaps better known for causing multidrug resistance in malignant tumours but also a drug transporter pump in the gut and kidneys and many other organs. P-glycoprotein in the gut pumps a drug back into the gut lumen, therefore, if the pump is inhibited, the result will be an increase in concentration of the substrate drug in the body.

The Adverse Drug Reactions Advisory Committee has received 2 reports of digoxin toxicity occurring in patients given roxithromycin. Both cases are consistent with roxithromycin inhibiting P-glycoprotein and hence increasing the net amount of absorption from the gut and reducing the renal excretion of digoxin. Both patients were on a dose of 250 µg digoxin daily.

Many, but not all, of the drugs which are transported by P-glycoprotein are also metabolized by cytochrome P4503A4 which can confuse the interpretation of interactions. This is not a problem with digoxin. Other common substrates for P-glycoprotein are cyclosporin, fluoroquinolones, HIV-protease inhibitiors, lignocaine, quinidine and ranitidine. Common inhibitors are diltiazem, verapamil and macrolide antibiotics. Prescribers should be aware of the potential for interactions caused by this mechanism.

Reference: Australian Adverse Drug Reactions Bulletin, Volume 20 (3), 2001.