Cimetidine 300mg four times daily for 7 days prolonged elimination half-life of a single 400mg dose of quinidine sulfate by 55%, from 5.8 to 9 hours,and decreased its clearance by 37 % in 6 healthy subjects. Peak plasma levels were raised by 21%. These changes were reflected in ECG changes, with 51 % and 28 % increases in mean areas under QT and QTc time curves, respectively, but these were not considered to be statistically significant (See reference number 1).
A later study in healthy subjects, prompted by observation of two patients who developed toxic quinidine levels when given cimetidine, found essentially same effects. The AUC and half-life of quinidine were increased by 14.5 and 22.6 % respectively, and clearance was decreased by 25 % by cimetidine 300mg four times daily (See reference number 2). A further study in 4 healthy subjects found that cimetidine 300mg four times daily for 5 days prolonged elimination half-life of quinidine by 54 % and decreased its total clearance by 36 % (See reference number 3,4). Cimetidine prolonged QT interval by 30 % more than effect of quinidine alone (See reference number 4). A case report describes marked increases in both quinidine and digitoxin concentrations in a woman also given cimetidine (See reference number 5). Similarly,quinidine levels increased by up to 50%, without causing any adverse effects, when a man taking quinidine was given cimetidine (See reference number 6).
It was originally suggested that cimetidine inhibits metabolism of quinidine by liver so that it is cleared more slowly (See reference number 2). However, further data suggest that cimetidine successfully competes with quinidine for its excretion by kidneys (See reference number 8).
The interaction between quinidine and cimetidine is established and of clinical importance. The incidence is unknown. Be alert for changes in response to quinidine if cimetidine is started or stopped. Ideally quinidine serum levels should be monitored and dosage reduced as necessary. Reductions of 25 % (oral) and 35 % (intravenous) have been suggested (See reference number 3). Those at greatest risk are likely to be patients with impaired renal function, patients with impaired liver function, elderly, and those with serum quinidine levels already at top end of therapeutic range (See reference number 2). The situation with ranitidine is uncertain.
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