Clozapine Cimetidine

Clinically important, potentially hazardous interactions with allopurinol, cimetidine, clozapine, metronidazole, phenytoin, warfarin... 

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. 

Drugs that may affect venlafaxine include cimetidine, cyproheptadine, and MAOIs. Drugs that may be affected by venlafaxine include clozapine, desipramine, haloperidol, indinavir, St. John s wort, trazodone, sibutramine, sumatriptan, and warfarin. 

Substrates Inhibitors Inducers CYP1A2 Acetaminophen, caffeine, clozapine, imipramine, theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole... 

Szymanski S, Lieberman JA, Picou D, et al. A case report of cimetidine-induced clozapine toxicity. J Clin Psychiatry 1991 52 21-22. 

D6 Tricyclic antidepressants (TCAs), benztropine, perphenazine, clozapine, haloperidol, codeine/oxycodone, risperidone, class Ic antiarrhythmics, 3 blockers, trazodone, paroxetine, maprotiline, amoxapine, duloxetine, mirtazapine (partly), venlafaxine, bupropion Fluoxetine, paroxetine, duloxetine, hydroxybupropion, methadone, cimetidine, haloperidol, quinidine, ritonavir Phenobarbital, rifampin... 

ANTIPSYCHOTICS-CHLORPROMAZINE, CLOZAPINE, HALOPERI-DOL, OLANZAPINE, PERPHENAZINE, RISPERIDONE, SERTINDOLE, THIORIDAZINE, ZUCLOPENTHIXOL H2 RECEPTOR BLOCKERS -CIMETIDINE t plasma concentrations of these antipsychotics, with risk of associated adverse effects Cimetidine is an inhibitor of CYP3A4 (sertindole, haloperidol, risperidone), CYP2D6 (chlorpromazine, risperidone, zudopenthixol, thioridazine, perphenazine) and CYP1A2 (clozapine, olanzapine, sertindole, haloperidol) Avoid concomitant use. Choose an alternative acid suppression, e.g. H2 antagonist... 

Carbamazepine is metabolized to an active 10,11-epoxide metabolite, thus medications that inhibit 3A4 isoenzymes may result in carbamazepine toxicity (e.g., cimetidine, dUtiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefa-zodone, propoxyphene, and verapamil). " When carbamazepine is combined with valproate, the carbamazepine dose should be reduced because valproate displaces carbamazepine from protein binding sites, thus increasing free levels." Combining clozapine and carbamazepine is not recommended because of the possibdity of bone marrow suppression with both agents. ... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip3rrine, atropine, aza-tadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorQrclizine, chlordiazepoxide, chlormezanone, cliloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazeptun, clonidine, clozapine, cocaine, codeine, colchicine, cgrclizine, cy-clobenzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem. 

A2 Cimetidine, fluoroquinolones, grapefruit juice, macrolides, isoniazid, zileuton Acetaminophen, clozapine, haloperidol, theophylline, tricyclic antidepressants, (R)-warfarin... 

Ampicillin, cefotaxime, ceftazidine, ciprofloxacin, methicillin, sulfathiazole, sulfamethoxazole Carbamazepine, felbamate, mesantoin, phenytoin, valproic acid Cimetidine, ranitidine Amodiaquin, chloroquine, quinine Chlorpromazine, clozapine, mianserin... 

A single case report describes increased serum clozapine levels and toxicity due to cimetidine, but not ranitidine. 

The suggested reason for this interaction is that the cimetidine (a potent non-specific enzyme inhibitor) reduces the metabolism of clozapine by the liver so that it aeeumulates, causing toxicity. Ranitidine does not cause enzyme inhibition and therefore does not interact. 

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