| Digoxin drug drug interactions: Pharmacokinetic interactions Pharmacokinetic interactions reported with digoxin involve drugs that affect its bioavailability, volume of distribution, tissue binding and excretion. In which alterations in bioavailability and excretion seem to have the greatest clinical significance. Drugs that decrease digoxin bioavailability • Example of Drugs that decrease digoxin bioavailability: • Cholestyramine • Colestipol • Cytotoxic agents • Sucralfate • Sulphasalazine Cholestyramine and colestipol are both anion exchange resins that bind to digoxin in the gastrointestinal tract and reduce its bioavailability. Thus, digoxin should be given 1.5 to 2 hours before either of these resins, to minimize the possibility of an interaction. Cytotoxic agents and/or radiotherapy can damage the lining of the intestine, which has been reported to reduce the absorption of digoxin tablets by almost 46 per cent. Patients on digoxin who are receiving such treatment should be monitored for signs of inadequate digitalisation. The absorption of liquid formulations of digoxin is not significantly reduced and these may be used as an alternative to tablets in such cases. The effects on absorption usually remain for about a week after treatment is withdrawn, so readjustment of digoxin therapy will then be required. • Examples of Drugs that increase digoxin bioavailability : • Amiodarone • Clarithromycin • Erythromycin • Propafenone • Quinidine • Tetracycline Approximately 10 per cent of patients treated with digoxin excrete it in substantial amounts in the faeces and urine as inactive metabolites. The gut flora, in particular Eubacterium lentum, seems to be responsible for this metabolism. When erythromycin, clarithromycin and tetracycline are given, they decimate these organisms and much more digoxin is available for absorption. This results in a marked rise in digoxin blood levels. Only those 10 per cent of patients who possess the ability to excrete digoxin in this manner are at risk from this interaction but it is not possible to predetermine who these patients will be. Therefore, all patients given these antibiotics while taking digoxin should be monitored for clinical symptoms of toxicity and a reduction in digoxin dose made, if necessary. Amiodarone, propafenone and quinidine also significantly increase serum digoxin levels. Although it has been suggested that this may be due to their ability to increase digoxin bioavailability, other mechanisms, particularly inhibition of digoxin excretion, are considered to be more significant. |
Drug Interactions
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