Possible Interaction: Mexiletine and Quinidine

“Other antiarrhythmics such as beta-blockers, calcium channel blockers, and amiodarone have been used effectively also; however, some antiarrhythmics such as lidocaine, mexiletine , propafenone, and quinidine may exacerbate neuromuscular symptoms and should be used cautiously.”

“EMs, but not PMs, are susceptible to drug interactions between mexiletine and drugs that inhibit CYP2D6 (e.g. quinidine).”

“In EM, quinidine decreased mexiletine total clearance from 621 +/- 298 to 471 +/- 214 ml/min (mean +/- S.D.; P less than .05) and mexiletine nonrenal clearance from 583 +/- 292 to 404 +/- 188 ml/min (P less than .05).”

“Moreover, quinidine increased mexiletine elimination half-life in EM from 9 +/- 1 to 11 +/- 2 h (P less than .05).”

“It is concluded that pretreatment with a very low dose of quinidine inhibits markedly the elimination of both major mexiletine metabolites (PHM and HMM) and likely decreases the overall elimination of mexiletine.”

“The total recovery of mexiletine and metabolites was significantly reduced after quinidine pretreatment.”

“Combination therapy with mexiletine and quinidine has been shown to be more effective than either agent alone.”

“In patients with refractory arrhythmias, the efficacy of mexiletine may be enhanced by combination with propranolol, quinidine or amiodarone.”

“Combining mexiletine with either beta-adrenergic blocking drugs or with quinidine markedly increases antiarrhythmic efficacy and substantially decreases the incidence of adverse effects.”

“Continuation of quinidine and withdrawal of mexiletine was associated with recurrence of complex ventricular arrhythmias and documented the need for combination treatment in nine patients.”

“In the group of 17 patients, the addition of a previously well-tolerated dosage of quinidine (824 + 298 mg) to a well-tolerated but only partially effective dosage of mexiletine (800 + 239 mg) produced a significantly greater antiarrhythmic response.”

“The addition of quinidine , which prolongs repolarization of the action potential in vitro, enhanced the antiarrhythmic efficacy of mexiletine , which shortens the action potential duration in vitro.”

“The coupling interval of the predominant ectopic beat prolonged (p < 0.05) during mexiletine treatment and further prolonged (p < 0.05) with the addition of quinidine.”

“In 8 additional patients no single drug tested was effective, and quinidine in combination with either mexiletine (7 patients) or propranolol (1 patient) prevented the initiation of VT during electrophysiologic testing.”

“In digitalized patients, quinidine increases serum digoxin concentration, increases digoxin's effect on atrioventricular conduction, and produces more adverse gastrointestinal effects than procainamide, disopyramide, or mexiletine.”