Drug Interactions between propafenone and Quin-G

GENERALLY AVOID: Coadministration of propafenone with Class IA antiarrhythmic agents such as quinidine may produce additive effects on the QT interval of the electrocardiogram. Theoretically, this may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death. Conflicting information exists as to whether propafenone alone prolongs the QT interval. Some clinicians suggest it does, although data in the medical literature do not support a clinically significant effect of propafenone and other Class IC agents on the QT interval. Moreover, because propafenone prolongs the QRS interval in the electrocardiogram, any changes in the QT interval are difficult to interpret. Nevertheless, proarrhythmic effects including sudden death and life-threatening ventricular arrhythmias such as ventricular fibrillation, ventricular tachycardia, asystole, and torsade de pointes have been associated with its use. Since propafenone has not been extensively studied for use in conjunction with other antiarrhythmic agents or agents that prolong the QT interval, caution may be advisable. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MONITOR CLOSELY: Coadministration with quinidine may alter the pharmacokinetics of propafenone and its active metabolite, 5-hydroxypropafenone, in some patients. The proposed mechanism is quinidine inhibition of the CYP450 2D6-mediated metabolism of propafenone. The interaction is observed in patients who are extensive metabolizers of debrisoquine (i.e., CYP450 2D6 extensive metabolizers). In nine patients who were receiving propafenone treatment for arrhythmia (all had dosage reduced to 150 mg every eight hours in anticipation of the interaction), coadministration with low-dose quinidine (50 mg three times a day) for four days increased the steady-state plasma concentration of propafenone by 2.7-fold and decreased that of 5-hydroxypropafenone by one-half in the seven patients who were CYP450 2D6 extensive metabolizers. Propafenone oral clearance was reduced by a mean of 58% in the presence of quinidine. The net effect of these changes has not been established. ECG intervals and arrhythmia frequency were not altered in the patients studied, which would suggest no substantial impact on the clinical response to propafenone. As expected, no changes in plasma propafenone and 5-hydroxypropafenone levels were observed in the two patients who were poor CYP450 2D6 metabolizers. In the general population, approximately 7% of Caucasians and 2% of Asians and individuals of African descent are thought to be poor CYP450 2D6 metabolizers. In another study conducted in healthy volunteers, investigators found evidence of increased beta-blocking effects of propafenone in extensive CYP450 2D6 metabolizers during coadministration with quinidine, presumably because only the parent drug (but not the metabolite) possesses beta-blocking activity. However, some clinicians have also used the combination therapeutically. One study in patients with refractory atrial fibrillation found that the addition of low-dose quinidine to propafenone was as effective as increasing the dosage of propafenone, but that the combination was better tolerated (less GI adverse effects).

MANAGEMENT: Propafenone product labeling for the sustained-release formulation recommends that concomitant use with Class IA and III antiarrhythmic agents be avoided. In addition, these agents should be withheld for at least 5 half-lives prior to dosing with propafenone. Close monitoring of clinical response, ECG, and drug levels is recommended if concomitant use with quinidine is required, and the propafenone dosage adjusted accordingly. In one study, average propafenone dosages were reduced by 45%. Patients should be advised to promptly notify their physician if they experience nausea, vomiting, fatigue, visual disturbances, headache, irregular heartbeats, changes in pulse rate, chest pain, or dyspnoea during treatment.

Switch to consumer interaction data