Ranitidine Dofetilide

Dofetilide is not administered with cimetidine because dofetilide plasma levels may be increased by as much as 50%. When treatment for gastric disorders is necessary, patients receiving dofetilide should take omeprazole ranitidine, or antacids as an alternative to cimetidine. 

In a randomized, placebo-controlled study of the effects of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of a single dose of dofetilide 500 micrograms in 20 healthy men, ranitidine 150 mg bd did not affect the pharmacokinetics or pharmacodynamics of dofetilide, but there was a dose-dependent increase in exposure to dofetilide with cimetidine (61). With cimetidine 100 and 400 mg bd the AUC of dofetilide increased by 11 and 48%, the maximum plasma dofetilide concentration increased by 11 and 29%, renal clearance fell by 13 and 33%, and non-renal clearance by 5 and 21% dofetilide-induced prolongation of the QT interval was increased by 22 and 33%. The authors suggested that cimetidine inhibited renal tubular dofetilide secretion,... 

Cimetidine markedly increases plasma dofetilide levels, and hence increases dofetilide-induced QT prolongation and the risk of torsade de pointes arrhythmias. Its combined use with dofetilide should be avoided. Dofetilide appears not to interact with ranitidine. 

An established interaction. Because of the likely increased risk of torsade de pointes, the manufacturer contraindicates the use of cimetidine in patients on dofetilide. This would seem to be a prudent precaution. This applies equally to cimetidine at over-the-counter doses, and patients on dofetilide should be warned to avoid this. No special precautions appear to be necessary with ranitidine. Note that omeprazole , (p.256) and antacids , (p.254) also appear not to interact with dofetilide. 

Abel S, Nichols DJ, Brearly CJ, Eve MD. Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide. BrJClin Pharmacol (2000) 49, 64-71. 

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