Mexiletine Theophylline

THEOPHYLLINE MEXILETINE Theophylline levels may be t by mexiletine cases of theophylline toxicity have been reported Mexiletine inhibits CYP1A2-mediated metabolism of theophylline 1 theophylline dose (by up to 50%). Monitor theophylline levels and watch for toxicity... 

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

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

Agents that may increase theophylline levels include allopurinol, beta blockers (nonselective), calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolides, mexiletine, quinolones, thiabendazole, thyroid hormones, carbamazepine, isoniazid, and loop diuretics. 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Acetaminophen Amiodarone Carbamazepine Cardiac glycosides Corticosteroids Dicumarol Disopyramide Doxycycline Estrogens Haloperidol Methadone Metyrapone Mexiletine Oral contraceptives Quinidine Theophylline Valproic acid Cyclosporine Dopamine Furosemide Levodopa Levonorgestrel Mebendazole Nondepolarizing muscle relaxant Phenothiazines Sulfonylureas... 

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. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

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. 

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

FIGURE 10.3 Effect of concomitantly administered mexiletine (Mx 200 mg Q8h) on the clearance of theophyUine (mean SD, p < 0.05) as determined by a retrospective analysis of theophylline pharmacokinetic data in 348 patients obtained from rontinely performed therapeutic drug monitoring. (Modified from Meibohm and Wegener. )... 

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. 

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. 

Serum theophylline levels are increased by mexiletine and toxicity may occur. Tocainide has only a small and probably clinically unimportant effect on theophylline pharmacokinetics. 

Mexiletine inhibits the metabolism (demethylation) of theophylline by the liver, thereby inereasing its effects. It is possible that the interaetion is due to eompetitive inhibition of the cytoehrome P450 isoenzyme CYP1A2. 3... 

The interaetion between theophylline and mexiletine is established and of elinical importanee. Monitor coneurrent use and reduee the theophylline dosage as necessary to prevent the development of theophylline toxieity. It has been suggested that 50% dose reduetions may be neeessary. It seems doubtful if the interaetion between theophylline and toeainide is elinically important but this needs eonfirmation. 

Ueno K, Miyai K, Seki T, Kawaguchi Y. Interaction between theophylline and mexiletine. DICP Ann Pharmacodier (1990) 24,471-2. 

Inafiiku M, Suzuki T, Ohtsu F, Hariya Y, Nagasawa K, Yoshioka Y, Nakahara Y, Hayakawa H. The effect of mexiletine on theophylline pharmacdcinetics in patients with bronchkl asthma. J Cardiol (1992) 22,227-33. 

EUiscm MJ, Lyman DJ, San Miguel E. Threefold increase in theophylline serum concentration after addition of mexiletine.y4m / >w r M <3 (1992) 10, 506-8. 

Loi C-M, Wei X, Vestal RE. Inhibition of theophylline metabolic by mexiletine in young male and female nonandcera. Clin Pharmacol 7% r(1991)49, 571-80. 

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