Mexiletine Disease Interactions
There are 6 disease interactions with mexiletine.
- Cardiovascular dysfunction
- Proarrhythmic effects
- AV node dysfunction
- Liver disease
- Renal dysfunction
- Seizures
Antiarrhythmics (applies to mexiletine) cardiovascular dysfunction
Major Potential Hazard, Low plausibility. Applicable conditions: Hypotension, Congestive Heart Failure
Antiarrhythmic agents can induce severe hypotension (particularly with IV administration) or induce or worsen congestive heart failure (CHF). Patients with primary cardiomyopathy or inadequately compensated CHF are at increased risk. Antiarrhythmic agents should be administered cautiously and dosage and/or frequency of administration modified in patients with hypotension or adequately compensated CHF. Alternative therapy should be considered unless these conditions are secondary to cardiac arrhythmia.
References
- Halkin H, Meffin P, Melmon KL, Rowland M "Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite." Clin Pharmacol Ther 17 (1975): 669-76
- Crouthamel WG "The effect of congestive heart failure on quinidine pharmacokinetics." Am Heart J 90 (1975): 335-9
- Ravid S, Podrid PJ, Lampert S, Lown B "Congestive heart failure induced by six of the newer antiarrhythmic drugs." J Am Coll Cardiol 14 (1989): 1326-30
- Swiryn S, Kim SS "Quinidine-induced syncope." Arch Intern Med 143 (1983): 314-6
- Gottlieb SS, Packer M "Deleterious hemodynamic effects of lidocaine in severe congestive heart failure." Am Heart J 118 (1989): 611-2
- Ochs HR, Grube E, Greenblatt DJ, Arendt R "Intravenous quinidine in congestive cardiomyopathy." Eur J Clin Pharmacol 19 (1981): 173-6
- Prescott LF, Adjepon-Yamoah KK, Talbot RG "Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure." Br Med J 1 (1976): 939-41
- "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories (2002):
- "Product Information. Xylocaine (lidocaine)." Astra-Zeneca Pharmaceuticals (2002):
- "Product Information. Quinidex Extentabs (quiNIDine)." Wyeth-Ayerst Laboratories
- "Product Information. Quiniglute (quinidine)." Berlex, Richmond, CA.
- "Product Information. Adenocard (adenosine)." Fujisawa (2001):
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
- Thomson P, Melmon K, Richardson J, Cohn K Steinbrunn W, Cudihee R, Rowland M "Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans." Ann Intern Med 78 (1973): 499-508
- Singh SN, Fletcher RD, Fisher SG, et al. "Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia." N Engl J Med 333 (1995): 77-82
- "Product Information. Cordarone (amiodarone)." Apothecon Inc (2022):
- "Product Information. Corvert (ibutilide)." Pharmacia and Upjohn (2001):
Antiarrhythmics (applies to mexiletine) proarrhythmic effects
Major Potential Hazard, High plausibility. Applicable conditions: Arrhythmias
Antiarrhythmic agents can induce or worsen ventricular arrhythmias. Ventricular tachycardia, ventricular fibrillation, and torsades de pointes have occurred in some patients. Patients with underlying cardiac dysfunction, bradycardia, hypokalemia, hypomagnesemia, or high antiarrhythmic serum concentrations are at increased risk for drug-induced arrhythmias. Therapy with antiarrhythmics should be used with extreme caution in patients with or predisposed to arrhythmias. Evidence of improved survival is lacking for use of antiarrhythmic therapy in asymptomatic, non-life-threatening arrhythmias. Therapy with antiarrhythmic agents should be reserved for patients with life-threatening arrhythmias.
References
- Anderson JL, Popat KD "Paradoxical ventricular tachycardia and fibrillation after intravenous bretylium therapy." Arch Intern Med 141 (1981): 801-2
- Sclarovsky S, Lewin RF, Kracoff O, Strasberg B, Arditti A, Agmon J "Amiodarone-induced polymorphous ventricular tachycardia." Am Heart J 105 (1983): 6-12
- Strasberg B, Sclarovsky S, Erdberg A, et al. "Procainamide-induced polymorphous ventricular tachycardia." Am J Cardiol 47 (1981): 1309-14
- Stratmann H, Walter K, Kennedy H "Torsade de pointes associated with elevated N-acetylprocainamide levels." Am Heart J 109 (1985): 375-6
- Lo KS, Gantz KB, Stetson PL, et al. "Disopyramide-induced ventricular tachycardia." Arch Intern Med 140 (1980): 413-4
- Kinney EL, Field EH, Salmon MP, Zelis R "Cardiac arrhythmias associated with disopyramide." N Engl J Med May (1990): 1146
- Chia BL "Disopyramide induced atypical ventricular tachycardia." Aust N Z J Med 10 (1980): 665-8
- Tzivoni D, Keren A, Stern S, Gottlieb S "Disopyramide-induced Torsade de pointes." Arch Intern Med 141 (1981): 946-7
- Schweitzer P, Mark H "Torsade de pointes caused by disopyramide and hypokalemia." Mt Sinai J Med 49 (1982): 110-4
- Riccioni N, Castiglioni M, Bartolomei C "Disopyramide-induced QT prolongation and ventricular tachyarrhythmias." Am Heart J 105 (1983): 870-1
- Andrivet P, Beaslay V, Canh VD "Torsades de pointe with flecainide-amiodarone therapy." Intensive Care Med 16 (1990): 342-3
- Cocco G, Strozzi C, Chu D, Pansini R "Torsades de pointes as a manifestation of mexiletine toxicity." Am Heart J 100 (1980): 878-80
- Nora MO, Chandrasekaran K, Hammill SC, Reeder GS "Prolongation of ventricular depolarization: ECG manifestation of mexiletine toxicity." Chest 95 (1989): 925-8
- Morganroth J, Pratt CM "Prevalence and characteristics of proarrhythmia from moricizine (themozine)." Am J Cardiol 63 (1989): 172-6
- Damle R, Levine J, Matos J, et al. "Efficacy and risks of moricizine in inducible sustained ventricular tachycardia." Ann Intern Med 116 (1992): 375-81
- Nathan AW, Hellestrand KJ, Bexton RS, Camm AJ "Fatal ventricular tachycardia in association with propafenone, a new class IC antiarrhythmic agent." Postgrad Med J 60 (1984): 155-6
- Stavens CS, McGovern B, Garan H, Ruskin JN "Aggravation of electrically provoked ventricular tachycardia during treatment with propafenone." Am Heart J 110 (1985): 24-9
- Hii JT, Wyse DG, Gillis AM, et al. "Propafenone-induced torsade de pointes: cross-reactivity with quinidine." Pacing Clin Electrophysiol 14 (1991): 1568-70
- Cheesman M, Ward DE "Exacerbation of ventricular tachycardia by tocainide." Clin Cardiol 8 (1985): 47-50
- Bauman JL, Bauernfeind RA, Hoff JV, et al. "Torsade de pointes due to quinidine: observations in 31 patients." Am Heart J 107 (1984): 425-30
- Koenig W, Schinz AM "Spontaneous ventricular flutter and fibrillation during quinidine medication." Am Heart J 105 (1983): 863-5
- Morganroth J, Horowitz LN "Incidence of proarrhythmic effects from quinidine in the outpatient treatment of benign or potentially lethal ventricular arrhythmias." Am J Cardiol 56 (1985): 585-7
- Au PK, Bhandari AK, Bream R, et al. "Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia." J Am Coll Cardiol 9 (1987): 389-97
- Engler RL, LeWinter M "Tocainide-induced ventricular fibrillation." Am Heart J 101 (1981): 494-6
- Wesley RC Jr, Turnquest P "Torsades de pointe after intravenous adenosine in the presence of prolonged QT syndrome." Am Heart J 123 (1992): 794-6
- Orebaugh SL, Handy M "Intravenous adenosine therapy accelerating rate of paroxysmal supraventricular tachycardia." Am J Emerg Med 10 (1992): 326-30
- Reed R, Falk JL, O'Brien J "Untoward reaction to adenosine therapy for supraventricular tachycardia." Am J Emerg Med 9 (1991): 566-70
- Meurer MK "A 21-year-old woman with rapid atrial fibrillation after adenosine administration." J Emerg Nurs 17 (1991): 135-6
- Dougherty AH, Gilman JK, Wiggins S, Jalal S, Naccarelli GV "Provocation of atrioventricular reentry tachycardia: a paradoxical effect of adenosine." Pacing Clin Electrophysiol 16 (1993): 8-12
- "Product Information. Tonocard (tocainide)." Merck & Co., Inc (2002):
- "Product Information. Ethmozine (moricizine)." DuPont Pharmaceuticals (2002):
- "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories (2002):
- "Product Information. Bretylol (bretylium)." DuPont Pharmaceuticals (2002):
- "Product Information. Xylocaine (lidocaine)." Astra-Zeneca Pharmaceuticals (2002):
- "Product Information. Procan SR (procainamide)." Parke-Davis (2001):
- "Product Information. Pronestyl (procainamide)." Apothecon Inc (2001):
- Raehl CL, Patel AK, LeRoy M "Drug-induced torsade de pointes." Clin Pharm 4 (1985): 675-90
- Buss J, Neuss H, Bilgin Y, Schlepper M "Malignant ventricular tachyarrhythmias in association with propafenone treatment." Eur Heart J 6 (1985): 424-8
- Sulke AN, Holt P, Sowton GE "Acceleration of conduction within an accessory pathway with propafenone." Int J Cardiol 28 (1990): 105-7
- "Product Information. Adenocard (adenosine)." Fujisawa (2001):
- "Product Information. Tambocor (flecainide)." 3M Pharmaceuticals (2001):
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
- "Product Information. Rythmol (propafenone)." Knoll Pharmaceutical Company
- Ben-Sorek ES, Wiesel J "Ventricular fibrillation following adenosine administration. A case report." Arch Intern Med 153 (1993): 2701-2
- Said SAM, Somer ST, Luttikhuis HAO "Flecainide-induced JT prolongation, t wave inversion and ventricular tachycardia during treatment for symptomatic atrial fibrillation." Int J Cardiol 44 (1994): 285-7
- Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH "Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs." JAMA 270 (1993): 2590-7
- "Product Information. Norpace (disopyramide)." Searle (2001):
- Oberg KC, Otoole MF, Gallastegui JL, Bauman JL "''late'' proarrhythmia due to quinidine." Am J Cardiol 74 (1994): 192-4
- Romer M, Candinas R "Adenosine-induced non-sustained polymorphic ventricular tachycardia." Eur Heart J 15 (1994): 281-2
- Hohnloser SH, Klingenheben T, Singh BN "Amiodarone-associated proarrhythmic effects - a review with special reference to torsade de pointes tachycardia." Ann Intern Med 121 (1994): 529-35
- Celiker A, Tokel K, Cil E, Ozkutlu S, Ozme S "Adenosine induced torsades de pointes in a child with congenital long QT syndrome." Pacing Clin Electrophysiol 17 (1994): 1814-7
- Exner DV, Muzyka T, Gillis AM "Proarrhythmia in patients with the Wolff-Parkinson-White Syndrome after standard doses of intravenous adenosine." Ann Intern Med 122 (1995): 351-2
- Williamson BD, Hummel J, Niebauer M, Man C, Strickberger SA, Daoud E, Morady F "Bradycardia-facilitated polymorphic ventricular tachycardia caused by amiodarone after radiofrequency modification of atrioventricular conduction." Am Heart J 130 (1995): 399-401
- Dhein S, Schott M, Gottwald E, Klaus W "Electrocardiological profile and proarrhythmic effects of quinidine, verapamil and their combination: a mapping study." Naunyn Schmiedebergs Arch Pharmacol 352 (1995): 94-101
- "Product Information. Cordarone (amiodarone)." Apothecon Inc (2022):
- Hohnloser SH, Vandeloo A, Baedeker F "Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine." J Am Coll Cardiol 26 (1995): 852-8
- "Product Information. Corvert (ibutilide)." Pharmacia and Upjohn (2001):
- Silverman AJ, Machado C, Baga JJ, Meissner MD, Lehmann MH, Steinman RT "Adenosine-induced atrial fibrillation." Am J Emerg Med 14 (1996): 300-1
- Boriani G, Biffi M, Frabetti L, Azzolini U, Sabbatani P, Bronzetti G, Capucci A, Magnani B "Ventricular fibrillation after intravenous amiodarone in wolff-parkinson-white syndrome with atrial fibrillation." Am Heart J 131 (1996): 1214-6
- Faggiano P, Gardini A, Daloia A, Benedini G, Giordano A "Torsade de pointes occurring early during oral amiodarone treatment." Int J Cardiol 55 (1996): 205-8
- Heisler BE, Ferrier GR "Proarrhythmic actions of flecainide in an isolated tissue model of ischemia and reperfusion." J Pharmacol Exp Ther 279 (1996): 317-24
- Strickberger SA, Man KC, Daoud EG, et al. "Adenosine-induced atrial arrhythmia: a prospective analysis." Ann Intern Med 127 (1997): 417-22
Mexiletine (applies to mexiletine) sinus (applies to mexiletine) AV node dysfunction
Major Potential Hazard, High plausibility. Applicable conditions: Heart Block
The use of mexiletine is contraindicated in patients with cardiogenic shock, second- or third-degree AV block in the absence of a functional artificial pacemaker.
References
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
Mexiletine (applies to mexiletine) liver disease
Moderate Potential Hazard, High plausibility.
Mexiletine is extensively metabolized by the liver to minimally active and inactive forms. The serum concentration of mexiletine is increased and the half-life prolonged in patients with liver impairment. Elevation of liver enzymes have been reported during the first few weeks of therapy, primarily in patients with congestive heart failure (CHF) or ischemia. Hepatic necrosis, resulting in death, has occurred. Therapy with mexiletine should be administered cautiously in patients with compromised liver function, CHF or ischemia. Clinical monitoring of cardiac function (ECG) and liver function is recommended.
References
- Pentikainen PJ, Hietakorpi S, Halinen MO, Lampinen LM "Cirrhosis of the liver markedly impairs the elimination of mexiletine." Eur J Clin Pharmacol 30 (1986): 83-8
- Nitsch J, Steinbeck G, Luderitz B "Increase of mexiletine plasma levels due to delayed hepatic metabolism in patients with chronic liver disease." Eur Heart J 4 (1983): 810-4
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
Mexiletine (applies to mexiletine) renal dysfunction
Moderate Potential Hazard, Moderate plausibility.
Mexiletine is primarily eliminated by the kidney. Approximately 10% of mexiletine is excreted in the urine unchanged. Marked changes in urinary pH alter the rate of mexiletine excretion. Elimination is accelerated with an acidic urinary pH and slowed with an alkaline urinary pH. Therapy with mexiletine should be administered cautiously in patients with significant renal impairment. Clinical monitoring of cardiac function (ECG) and renal function is recommended.
References
- Wang T, Wuellner D, Woosley RL, Stone WJ "Pharmacokinetics and nondialyzability of mexiletine in renal failure." Clin Pharmacol Ther 37 (1985): 649-53
- El Allaf D, Henrard L, Crochelet L, Delapierre D, Carlier J, Dresse A "Pharmacokinetics of mexiletine in renal insufficiency." Br J Clin Pharmacol 14 (1982): 431-5
- Guay DR, Meatherall RC, Ferguson I, Smith H, Light B "Mexiletine clearance during peritoneal dialysis ." Br J Clin Pharmacol 19 (1985): 857-8
- Jones TE, Reece PA, Fisher GC "Mexiletine removal by peritoneal dialysis." Eur J Clin Pharmacol 25 (1983): 839-40
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
Mexiletine (applies to mexiletine) seizures
Moderate Potential Hazard, Low plausibility.
Seizures have been reported rarely during mexiletine therapy in patients with and without a history of seizures. Therapy with mexiletine should be administered cautiously in patients with or predisposition to seizure disorders.
References
- "Product Information. Mexitil (mexiletine)." Boehringer-Ingelheim (2001):
Mexiletine drug interactions
There are 134 drug interactions with mexiletine.
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Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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