Mexiletine interaction

Mexiletine interacts with antacids, but the interaction is unlikely to be clinically important (48). 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Yonezawa E, Matsumoto K, Ueno K, Tachibana M, Hashimoto H, Komamura K, Kamakura S, Miyatake K, Tanaka K. Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients. J Clin Pharmacol 2002 42(3) 342-6. 

Mexiletine reduces the clearance of theophylline, and this combination has been reported to cause ventricular tachycardia (52). A similar interaction tvith caffeine has been reported (53). 

Kessler KM, Interian A Jr, Cox M, Topaz O, De Marchena EJ, Myerburg RJ. Proarrhythmia related to a kinetic and dynamic interaction of mexiletine and theophylline. Am Heart J 1989 117(4) 964-6. 

An interaction of lidocaine with mexiletine, which resulted in toxic concentrations of lidocaine, has been reported (79). 

Maeda Y, Funakoshi S, Nakamura M, Fukuzawa M, Kugaya Y, Yamasaki M, Tsukiai S, Murakami T, Takano M. Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine. Clin Pharmacol Ther 2002 7I(5) 389-97. 

Mexiletine is a class Ib antidysrhythmic drug, similar in action to lidocaine, but it can be given orally. Its adverse effects occur in up to 50% of patients (1) and withdrawal is often necessary (2). The most common adverse effects are on the cardiovascular and central nervous systems. The pharmacokinetics, clinical use, and adverse effects and interactions of mexiletine have been reviewed widely (3-8). 

Interactions of mexiletine with other cardioactive drugs have been reviewed (48). The most important are beneficial interactions with beta-adrenoceptor antagonists, quinidine, and amiodarone in the suppression of ventricular tachydysrhythmias. During these interactions the... 

Mexiletine is metabolized mainly by CYP2D6 and CYP1A2. Omeprazole is an inducer of CYP1A2 and might therefore be expected to interact with mexiletine. However, in a study in nine healthy men there was no evidence of an effect of steady-state omeprazole 40 mg/ day on the single-dose kinetics of mexiletine 200 mg (50). 

Bigger JT Jr. The interaction of mexiletine with other cardiovascular drugs. Am Heart J 1984 107(5 Pt 2) 1079-85. 

Kusumoto M, Ueno K, Tanaka K, Takeda K, Mashimo K, Kameda T, Fujimura Y, Shibakawa M, Guzman WM, Laplante S. Lack of pharmacokinetic interaction between mexiletine and omeprazole. Ann Pharmacother 1998 32(2) 182-4. 

Labbe L, O Hara G, Lefebvre M, Lessard E, Gilbert M, Adedoyin A, Champagne J, Hamelin B, Turgeon J. Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther 2000 68(l) 44-57. 

The interaction of rifampicin with mexiletine has been reviewed (105). The mean half-life of a single dose of mexiletine 400 mg fell from 8.5 to 5 hours in eight healthy subjects who took rifampicin 600 mg/day for 10 days (119). 

Glynn-Bamhart, A. M. et al., Effect of low-dose methotrexate on the disposition of glucocorticoids and theophylline, J. Allergy Clin. Immunol., 88(2) 180-186, 1991. Ueno, K. et al., Mechanism of interaction between theophylline and mexiletine. Drug Intell. Clin. Pharm., 25(7-8) 727-730, 1991. 

Meibohm, B. and Wegener, S., Mexiletine-Theophylline-Interaction, Krankenhaus-pharmazie, 13(7) 331-333, 1992. 

Ueno K, Yamaguchi R, Tanaka K, Sakaguchi M, Morishima Y, Yamauchi K, Iwai A. Lack of a kinetic interaction between fluconazole and mexiletine. EurJ Clin Pharmacol (1996) 50, 129-31. 

An established interaction although information is limited. The delay and reduction in the absorption would seem to limit the value of oral mexiletine during the first few hours after a myocardial infarction, particularly if opioid analgesics are used. The manufacturer suggests that a higher load-... 

Information seems to be limited to this report but the interaction appears to be established. It seems likely that the fall in mexiletine levels will be clinically important in some individuals. Monitor for mexiletine efficacy, and where possible levels. Raise the dosage if necessary. 

Fluvoxamine markedly increases the AUC of mexiletine by inhibiting CYP1A2. Fluoxetine and paroxetine might also be expected to interact, albeit by inhibiting CYP2D6, but sertraline is possibly unlikely to interact. 

Mexiletine is also metabolised by CYP2D6 (e.g. see Mexiletine + Propafenone , p.269). In an in vitro study using human liver microsomes, paroxetine, fluoxetine, and sertraline extensively inhibited the metabolism of mexiletine. Using a model to prediet in vivo interactions, it was suggested that both fluoxetine and paroxetine may interact with mexiletine to a clinically relevant extent, whereas sertraline is less likely to interact. ... 

The UK manufacturer notes that it may be neeessary to reduce the dose of mexiletine when used concurrently with drugs causing inhibition of hepatic enzymes, in particular the cytochrome P450 isoenzymes CYP1A2 and CYP2D6, which is consistent with the proposed mechanism of the interaction. 

Kara Y, Nakajima M, Miyamoto K-I, Yokoi T. Inhibitory effects of psychotropic drugs on mexiletine metabolism in human liver microsomes prediction of in vivo drug interactions. Xe-nobiotica (2005) 35, 549-60. 

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