Mexiletine Phenytoin

MEXILETINE ANTIEPILEPTICS Phenytoin levels are i by mexiletine Phenytoin induces CYP1A2-medi-ated metabolism of mexiletine Watch for poor response to mexiletine... 

Na+ Anticonvulsant drugs Class I antiarrhythmics Diuretic drugs Local anesthetic drugs Carbamazepine, phenytoin, valproic acid lA Disopyramide, procainamide, quinidine IB Lidocaine, mexiletine, phenytoin, tocainide IC Encainide, flecainide, propafenone Amiloride Bupivacaine, cocaine, lidocaine, mepivacaine, tetracaine... 

Selertive serotonin reuptake inhibitors may decrease metabolism of alpha/beta blockers, benzodiazepines, carbamazepine, cimetidine, clozapine, fesoterodine, haloperidol, methadone, mexiletine, phenytoin, propafenone, respiradone, tamoxifen, galantamine, respiradone, thioridazine. 

I b With shortening of action potential Lidocaine, Mexiletine, Tocainide, Phenytoin, Aprindine... 

Antiarrhythmics representative of these categories include Class lA— quinidine, procainamide, ajmaline, dis-opyramide, propafenone Class IB—lido-caine, mexiletine, tocainide, as well as phenytoin Qass 1C—flecainide. 

IB (tocainide, lidocaine, phenytoin, mexiletine) - Depress phase 0 slightly and may shorten the action potential duration. Although arrhythmia is not a labeled indication for phenytoin, it is commonly used in treatment of digitalis-induced arrhythmias. 

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. 

IB Lidocaine Phenytoin Tocainide Moricizine Mexiletine Minimally change V , of phase 0, decrease cardiac action potential duration, decrease inward sodium current in ventricular muscle, increase outward potassium current. 

An upward adjustment in dose may be required when mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration. 

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

Sulfonamides, penicillins, diclofenac, oxyphenbutazone, piroxicam, phenytoin, carbamazepine (Same as for erythema multiforme) penicillamine, captopril, piroxicam, penicillins, rifampicin Frusemide, penicillamine, penicillin, PUVA therapy Immunosuppressants, mexiletine, thioridazine, penicillamine, moduretic , atenolol, quinacrine... 

Traditional local anaesthetics (lidocaine), antiarrhythmics (mexiletine) and anticonvulsants (phenytoin), antipsychotics (carbamazepine) and anti-depressants (amitriptyline) have all been used clinically, with substantial interpatient... 

This class includes lidocaine, phenytoin. tocainide and mexiletine. 

The observation that 3 patients had unusually low plasma mexiletine levels while taking phenytoin prompted a pharmacokinetic study in 6 healthy subjects. After taking phenytoin 300 mg daily for a week, the mean AUC and half-life of a single 400-mg dose of mexiletine were reduced by an average of about 50% (half-life reduced from 17.2 to 8.4 hours). ... 

The most likely explanation is that phenytoin increases the metabolism of mexiletine by the cytochrome P450 isoenzyme CYP1A2. 

Begg EJ, Chinwah PM, Webb C, Day RO, Wade DN. Enhanced metabolism of mexiletine after phenytoin administration. BrJ Clin Pharmacol ( 9S2) 14, 219-23. 

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