Initial dosage selection of antiarrhythmic therapy

The success or failure of antiarrhythmic drug treatment depends, in part, on the selection of the initial dosage. Too low a dosage can lead to unnecessary (and frequently life-endangering) delays in achievement of arrhythmia suppression. Conversely, an excessively high dosage can lead to intolerable toxicity and cessation of treatment. The recommended approach to therapy is to begin with a relatively low dosage, i.e., the lowest dosage with a reasonable chance of producing a favorable response, and titrating the dose upward as needed. Dose titration should be guided by clinical response and, when appropriate, concentrations of the drug and any active metabolites in the plasma. In situations frequently encountered in practice, however, the initial dosage must be modified because of interindividual differences in drug disposition. These changes in drug pharmacokinetics can arise from a variety of factors, including disease processes (e.g., congestive heart failure, cirrhosis and renal failure), concomitant medications (e.g., hepatic enzyme inducers such as phenytoin and inhibitors such as amiodarone), drug formulation, protein binding and inherited drug metabolism capacity. Knowledge of these factors can help the clinician to avoid potential pitfalls in initial dosage selection and can enhance the changes of successful drug treatment of arrhythmias.