OBJECT DRUGS

Antiarrhythmics (CYP3A4 Substrates):

• Amiodarone (Cordarone, etc.)
• Disopyramide (Norpace, etc.)
• Dronedarone (Multaq)
• Quinidine (Quinidex)

PRECIPITANT DRUGS

Enzyme Inducers:

• Barbiturates
• Bosentan (Tracleer)
• Carbamazepine (Tegretol, etc.)
• Dabrafenib (Tafinlar)
• Dexamethasone (Decadron, etc.)
• Efavirenz (Sustiva)
• Lumacaftor (Orkambi)
• Nevirapine (Viramune, etc.)
• Oxcarbazepine (Trileptal, etc.)
• Phenytoin (Dilantin, etc.)
• Primidone (Mysoline)
• Rifabutin (Mycobutin)
• Rifampin (Rifadin, etc.)
• Rifapentine (Priftin)
• St. John's Wort

Comment:

CYP3A4 is quite sensitive to enzyme induction, and enzyme inducers have been shown to reduce plasma concentrations of these antiarrhythmic drugs. Depending on the potency of the enzyme inducer, the reductions in antiarrhythmic plasma concentrations may result in substantial reductions in antiarrhythmic effects. Note also that some of these antiarrhythmics inhibit various enzyme and transporters (see CYP table), and may affect the plasma concentrations of the enzyme inducer. It has also been proposed that amiodarone is converted to hepatotoxic metabolites by CYP3A4; thus, inducers of CYP3A4 might increase the hepatotoxicity of amiodarone.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• St. John's wort: Given the limited evidence of efficacy, St. John's wort should generally be avoided in patients taking one of these antiarrhythmic agents.
• Monitor: Monitor for altered antiarrhythmic response if the CYP3A4 inducer is initiated, discontinued, or changed in dosage. Monitor for ECG changes indicating loss of antiarrhythmic efficacy, and measure antiarrhythmic plasma concentrations as needed. Note that the effect of enzyme inducers is often gradual, and it can take up to 1 to 2 weeks for maximal effects, and from 1 to 4 weeks for the effect to dissipate (depending on which inducer is used).