Potentially significant drug interactions of class III antiarrhythmic drugs.
Article Details
- CitationCopy to clipboard
Yamreudeewong W, DeBisschop M, Martin LG, Lower DL
Potentially significant drug interactions of class III antiarrhythmic drugs.
Drug Saf. 2003;26(6):421-38. doi: 10.2165/00002018-200326060-00004.
- PubMed ID
- 12688833 [ View in PubMed]
- Abstract
Class III antiarrhythmic drugs, especially amiodarone (a broad-spectrum antiarrhythmic agent), have gained popularity for use in clinical practice in recent years. Other class III antiarrhythmic drugs include bretylium, dofetilide, ibutilide and sotalol. These agents are effective for the management of various types of cardiac arrhythmias both atrial and ventricular in origin. Class III antiarrhythmic drugs may interact with other drugs by two major processes: pharmacodynamic and pharmacokinetic interactions. The pharmacodynamic interaction occurs when the pharmacological effects of the object drug are stimulated or inhibited by the precipitant drug. Pharmacokinetic interactions can result from the interference of drug absorption, metabolism and/or elimination of the object drug by the precipitant drug. Among the class III antiarrhythmic drugs, amiodarone has been reported to be involved in a significant number of drug interactions. It is mainly metabolised by cytochrome P450 (CYP)3A4 and it is a potent inhibitor of CYP1A2, 2C9, 2D6 and 3A4. In addition, amiodarone may interact with other drugs (such as digoxin) via the inhibition of the P-glycoprotein membrane transporter system, a recently described pharmacokinetic mechanism of drug interactions. Bretylium is not metabolised; it is excreted unchanged in the urine. Therefore the interactions between bretylium and other drugs (including other antiarrhythmic drugs) is primarily through the pharmacodynamic mechanism. Dofetilide is metabolised by CYP3A4 and excreted by the renal cation transport system. Drugs that inhibit CYP3A4 (such as erythromycin) and/or the renal transport system (such as triamterene) may interact with dofetilide. It appears that the potential for pharmacokinetic interactions between ibutilide and other drugs is low. This is because ibutilide is not metabolised by CYP3A4 or CYP2D6. However, ibutilide may significantly interact with other drugs by a pharmacodynamic mechanism. Sotalol is primarily excreted unchanged in the urine. The potential for drug interactions due to hepatic enzyme induction or inhibition appears to be less likely. However, a number of drugs (such as digoxin) have been reported to interact with sotalol pharmacodynamically. If concurrent use of a class III antiarrhythmic agent and another drug cannot be avoided or no published studies for that particular drug interaction are available, caution should be exercised and close monitoring of the patient should be performed in order to avoid or minimise the risks associated with a possible adverse drug interaction.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Amiodarone Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails Amiodarone Cytochrome P450 2D6 Protein Humans NoInhibitorDetails Dofetilide Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAdenosineAmiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Adenosine. AtropineAmiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Atropine. BepridilAmiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Bepridil. BioallethrinAmiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Bioallethrin. BretyliumAmiodarone The risk or severity of adverse effects can be increased when Amiodarone is combined with Bretylium. - Food Interactions
Drug Interaction Dofetilide Exercise caution with St. John's Wort. Dofetilide is partially metabolized by CYP3A4, and St. John's Wort is a CYP3A4 inducer, coadministration may reduce dofetilide serum levels.