Mexiletine Caffeine

Drugs that may be affected by mexiletine include cimetidine, caffeine, and theophylline. 

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

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). 

Also analyzed acebutolol, acetaminophen, alprazolam, amphetamine, atenolol, betaxolol, brotizolam, caffeine, camazepam, captopril, chloroquine, clobazam, clomipramine, cloth-iapine, clotiazepam, cloxazolam, cocaine, codeine, diclofenac, dihydralazine, dihydrocodeine, dihydroergotamine, diphenhydramine, domperidone, doxepin, droperidol, ergota-mine, ethyl loflazepate, fenethylline, fluoxetine, flupentixol, flurazepam, furosemide, gliclazide, hydrochlorothiazide, hydroxyzine, ibuprofen, imipramine, ketazolam, loprazo-1am, lorazepam, lormetazepam, maprotUine, medazepam, mepyramine, methadone, methaqualone, methyldopa, methylphenidate, metoclopramide, metoprolol, mexiletine, mianserin, midazolam, minoxidil, morphine, nadolol, nitrazepam, oxprenolol, papaverine, pentazocine, phenprocoumon, phenylbutazone, pipamperone, piritramide, practolol, pra-zepam, prazosin, promazine, promethazine, propoxyphene, propranolol, prothipendyl, quinine, sotalol, sulpride, thioridazine, trazodone, triazolam, trimipramine, tripelennamine, lyramine, verapeunil, yohimbine... 

Simultaneous caffeine, chlorthahdone, diclofenac, estriol, furosemide, phenacetin, phen-obarbital, theobromine, theophylline, triamterene Noninterfering edhuterol, amiloride, atenolol, mexiletine, tiapride... 

In more recent studies, Turgeon and colleagues have reported the effects of coadministration of caffeine [131] or propafenone [132] on the stereoselective pharmacokinetics of mexiletine in poor and extensive metabolizers of debrisoquine. Caffeine, a substrate for CYP1A2, did not significantly change the plasma eoncentrations of mexiletine enantiomers in either PMs or EMs [131]. However, it resulted in a slight decrease ( 15%) in the urinary recovery of N-hydroxymexiletine generated from the R enantiomer in both EMs and PMs [131]. The metabolism of the S enantiomer was not affected because the N-hydroxymexiletine recovered in urine is mostly from the R enantiomer. 

In contrast to caffeine, propafenone coadministration significantly reduced the metabolism of both enantiomers of mexiletine in EMs [132]. However, it did not have a significant effect on the pharmacokinetics of mexiletine enantiomers in PMs. In fact, after coadministration of propafenone to EMs, the plasma concentration-time profiles and pharmacokinetics of mexiletine enantiomers in these subjects were not distinguishable from those in PMs [132]. These results are in agreement with the inhibitory effects of propafenone on the CYP2D6 pathway and are similar to those obtained with quinidine, another CYP2D6 inhibitor (Table 13). 

Labbe, L. Abolfathi, Z. Robitaille, N.M. St-Maurice, F. Gilbert, M. Turgeon, J. Stereoselective disposition of the antiarrhythmic agent mexiletine during the concomitant administration of caffeine. Ther. Drug. Monit. 1999, 21, 191-199. 

Caffeine clearance is reduced by 30 to 60% by mexiletine, resulting in raised serum caffeine levels. Whether this might result in caffeine toxicity is uncertain. Lidocaine, flecainide and tocainide do not appear to affect caffeine clearance. Caffeine does not significantly alter mexiletine levels. 

Another study in 14 healthy subjects found that caffeine 100 mg four times daily, for 2 days before and 2 days after mexiletine, did not cause any significant changes in the plasma levels of a single 200-mg dose of mexiletine. Caffeine levels tended to be increased 24 hours after taking mexiletine. ... 

It is likely that, as with theophylline (see Theophylline + Mexiletine or Tocainide, p.ll88), mexiletine inhibits the hepatic metabolism of caffeine by the cytochrome P450 isoenzyme CYP1A2. 

The interaction between caffeine and mexiletine appears to be established, but its clinical importance is uncertain. Some of the adverse effects of mexiletine might be partially due to caffeine-retention (from drinking tea, coffee, cola drinks, etc.). In excess, caffeine can cause jitteriness, tremor and insomnia. It has also been suggested that the caffeine test for liver function might be impaired by mexiletine. Be alert for these possible effects. 

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