Interaction between Disopyramide and Amiodarone
Major
Metabolism
| ID | DDInter575 and DDInter76 |
| Interaction | Coadministration of amiodarone and disopyramide may increase the risk of new arrhythmias due to additive depressant effects on cardiac conduction. There have been reports of torsade de pointes arrhythmia in association with significantly prolonged QT interval ranging from over 500 to 680 msec in patients receiving concomitant therapy. Serious exacerbation of preexisting arrhythmia may also be more likely during coadministration relative to either agent alone. Despite the potential toxicities, amiodarone and disopyramide have been used together successfully in the treatment of certain ventricular arrhythmias. Amiodarone is an inhibitor of CYP450 3A4 and may increase the plasma concentrations of disopyramide, which is primarily metabolized by the isoenzyme. Due to the long and variable half-life of amiodarone, potential for interaction may exist even after its discontinuation. |
| Management | The concurrent use of amiodarone with other antiarrhythmic agents, including disopyramide, should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent or to amiodarone alone. In general, if adding or transferring to oral amiodarone, the dosages of previously administered agents should be reduced by 30% to 50% several days after initiation of amiodarone, when onset of arrhythmia suppression is expected to occur. The continued need for other antiarrhythmic agents should be evaluated after the effects of amiodarone have been established, and discontinuation should ordinarily be attempted. If the combination is continued, patients should be monitored closely for adverse effects including conduction disturbances and exacerbation of tachyarrhythmias. Conversely, in amiodarone-treated patients who require additional antiarrhythmic agents, the initial dosage of such agents should be approximately one-half the usual recommended dosage. All patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath, or syncope. |
| References | |
| Alternative for Disopyramide |
C01B
|
| Alternative for Amiodarone |
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.