PHENYTOIN, CARBAMAZEPINE AND OTHER ENZYME INDUCING AGENTS REDUCES THE PLASMA CONCENTRATION OF CLOZEPINE. SEDATIVES INCREASE THE SEDATIVE PROPERTIES OF CLOZAPINE. BECAUSE CLOZAPINE IS HIGHLY BOUND TO SERUM PROTEIN, ADMINISTRATION OF CLOZAPINE TO A PATIENT TAKING ANOTHER DRUG WHICH IS HIGHLY BOUND TO PROTEIN (E.G., WARFARIN, DIGITOXIN) MAY CAUSE AN INCREASE IN PLASMA CONCENTRATIONS OF THESE DRUGS, POTENTIALLY RESULTING IN ADVERSE EFFECTS. CIMETIDINE, ERYTHROMYCIN AND SELECTIVE SEROTONIN REUPTAKE INHIBITORS LIKE FLUOXETINE & FLUVOXAMINE MAY INCREASE PLASMA LEVELS OF LOZAPIN. CONCOMITANT USE OF CLOZAPINE WITH OTHER DRUGS METABOLIZED BY CYTOCHROME P450 2D6 MAY REQUIRE LOWER DOSES THAN USUALLY PRESCRIBED FOR EITHER CLOZAPINE OR THE OTHER DRUG. THEREFORE, CO- ADMINISTRATION OF CLOZAPINE WITH OTHER DRUGS THAT ARE METABOLIZED BY THIS ISOZYME, INCLUDING ANTIDEPRESSANTS, PHENOTHIAZINES, CARBAMAZEPINE, AND TYPE 1C ANTIARRHYTHMICS (E.G., PROPAFENONE, FLECAINIDE AND ENCAINIDE), OR THAT INHIBIT THIS ENZYME (E.G., QUINIDINE), SHOULD BE APPROACHED WITH CAUTION. CLOZAPINE MAY ALSO POTENTIATE THE HYPOTENSIVE EFFECTS OF ANTIHYPERTENSIVE DRUGS AND THE ANTICHOLINERGIC EFFECTS OF ATROPINE-TYPE DRUGS. THE ADMINISTRATION OF EPINEPHRINE SHOULD BE AVOIDED IN THE TREATMENT OF DRUG INDUCED HYPOTENSION BECAUSE OF A POSSIBLE REVERSE EPINEPHRINE EFFECT.