Drug Interactions between digitoxin and kaolin

ADJUST DOSING INTERVAL: Concurrent administration of kaolin-pectin may decrease the oral bioavailability of digitalis glycosides. The mechanism of interaction is unknown. In a single-dose study, simultaneous administration of a kaolin-pectin suspension and an oral dose of digoxin resulted in delay of absorption and a 62% reduction in the bioavailability of digoxin. Intersubject variation in digoxin bioavailability also increased more than twofold in the presence of kaolin-pectin. In contrast, administration of kaolin-pectin 2 hours before the digoxin dose had no effect on digoxin absorption rate but reduced digoxin bioavailability by 20%, while administration 2 hours after the digoxin dose neither affected the rate nor extent of absorption of digoxin. Also, no change in intersubject variability in digoxin bioavailability was observed when administration times were separated. In seven patients receiving chronic oral digoxin therapy, simultaneous administration of a kaolin-pectin antidiarrheal mixture decreased steady-state digoxin peak levels (Cmax) by 36% and the 24-hour area under the concentration-time curve (AUC) by 15%. When kaolin-pectin was administered 2 hours before or 2 hours after digoxin, no evidence of an interaction was observed. In ten healthy volunteers, administration of a single 0.75 mg dose of digoxin with kaolin-pectin significantly reduced the cumulative six-day urinary digoxin excretion (expressed as the percentage of original dose recovered) compared to administration without (23.4% vs. 40.1%). In another study, coadministration with 60 mL of a commercial kaolin-pectin suspension had no effect on the 24-hour AUC of digoxin administered as two 0.2 mg capsules or tablets, although the digoxin Cmax from both formulations was reduced, and the 24-hour digoxin urinary recovery from the tablets tended to be reduced.

MANAGEMENT: To minimize the potential for interaction, patients should be advised to take kaolin-pectin at least 2 hours after digoxin if possible. The same precaution may be applicable during therapy with digitoxin, although clinical data are lacking.