Dofetilide Cimetidine

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. 

Dofetilide See below3 patients must be hospitalized for 3 days during initiation of therapy Cimetidine, hy d roch I o roth iaz i de, ketoconazole, medroxyprogesterone, promethazine, trimethoprim, verapamil (all inhibit dofetilide elimination)... 

Verapamil increases serum dofetilide levels, as do drugs that inhibit cationic renal secretion, such as ketoconazole and cimetidine, raise serum levels. 

Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dosage must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the rate-corrected QT interval (QTC) and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 bpm and hypokalemia are relative contraindications to its use. 

Renal All aminoglycosides, vancomycinm, digoxin, procainamide, lithium, sotalof atenolof dofetilide, 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. 

At least 50% of a dofetilide dose is eliminated unchanged in the urine by an active renal tubular secretion mechanism. Drugs that inhibit this mechanism, such as cimetidine, increase dofetilide plasma levels.There... 

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. 

Vincent J, Gardner MJ, Apseloff G, Baris B, Willavize S, Friedman HL. Cimetidine inhibits renal elimination of dofetilide without altering QTc activity onmultiple dosing in healthy subjects. Clin Pharmacol Ther (1998) 63, 210. 

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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