Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction.

1 Thirty patients on maintenance digoxin therapy and admitted for cardioversion of atrial fibrillation were closely monitored with regard to plasma levels of digoxin and quinidine. 2 Seventeen of these patients were kept on maintenance digoxin therapy. After an initial lag period of 6 to 18 h after the addition of quinidine their digoxin levels started to increase and had increased by between 20 and 330% after 3 days on quinidine. Side-effects attributed to the raised digoxin concentration occurred in 6 of these patients. 3 As studied in 5 of these 17 patients the renal clearance of digoxin decreased markedly when quinidine was added to the therapy. There was also a slight but significant reduction in creatinine clearance (n = 4). 4 In 13 patients digoxin was discontinued 36 h prior to the first quinidine dose. Also in these patients digoxin plasma levels increased significantly. 5 It is concluded that quinidine causes an unpredictably large increase in plasma digoxin and that this effect is probably at least initially to a large part due to a redistribution of digoxin in the body. The relative contributions of re-distribution and impaired renal clearance of digoxin to the increase in digoxin steady-state levels are presently unknown. 6 It is recommended that close monitoring of digoxin concentration and appropriate reduction of the maintenance dose is undertaken when quinidine is to be given to patients on digitalis therapy.