Interaction between Dofetilide and Bretylium
Major Synergy

ID DDInter580 and DDInter229
Interaction Dofetilide should not be used with Class I or other Class III antiarrhythmic agents due to the potential for additive effects on myocardial refractoriness. Many of these agents, including dofetilide, can also cause prolongation of the QT interval, thus concomitant use may increase the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes.
Management Class I (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, ibutilide, sotalol) antiarrhythmic agents should be withheld for at least 3 half-lives before administering dofetilide. In the case of amiodarone with its unpredictable pharmacokinetics, dofetilide should not be initiated until serum amiodarone levels are below 0.3 mcg/mL or amiodarone has been withdrawn for at least three months.
References
Alternative for Dofetilide C01B
Alternative for Bretylium C01B

Potential Metabolism Interactions

Substrate-Substrate Interaction:If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction:Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction:Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.