circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.benzphetamineperphenazine, benzphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.perphenazine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.amitriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.benztropinebenztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use. perphenazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .bethanecholbethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.brexanolonebrexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.brexpiprazolebrexpiprazole and amitriptyline both increase sedation. Use Caution/Monitor.brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.brimonidinebrimonidine and perphenazine both increase sedation. Use Caution/Monitor.brimonidine and amitriptyline both increase sedation. Use Caution/Monitor.brivaracetambrivaracetam and amitriptyline both increase sedation. Use Caution/Monitor.brivaracetam and perphenazine both increase sedation. Use Caution/Monitor.brompheniraminebrompheniramine and amitriptyline both increase sedation. Use Caution/Monitor.brompheniramine and perphenazine both increase sedation. Use Caution/Monitor.buprenorphinebuprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor.buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine buccalbuprenorphine buccal and amitriptyline both increase sedation. Use Caution/Monitor.buprenorphine buccal and perphenazine both increase QTc interval. Use Caution/Monitor.buprenorphine buccal and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine subdermal implantbuprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.amitriptyline, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.buprenorphine subdermal implant and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine transdermalbuprenorphine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.buprenorphine transdermal and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine, long-acting injectionamitriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.buprenorphine, long-acting injectionperphenazine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.buprenorphine, long-acting injection and perphenazine both increase QTc interval. Use Caution/Monitor.buprenorphine, long-acting injection and perphenazine both increase sedation. Use Caution/Monitor.bupropionbupropion will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.butabarbitalbutabarbital and perphenazine both increase sedation. Use Caution/Monitor.butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.butabarbital and amitriptyline both increase sedation. Use Caution/Monitor.butalbitalbutalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.butalbital and perphenazine both increase sedation. Use Caution/Monitor.butalbital and amitriptyline both increase sedation. Use Caution/Monitor.butorphanolbutorphanol and perphenazine both increase sedation. Use Caution/Monitor.butorphanol and amitriptyline both increase sedation. Use Caution/Monitor.caffeineperphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.carbacholcarbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.carbinoxaminecarbinoxamine and perphenazine both increase sedation. Use Caution/Monitor.carbamazepinecarbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.carbinoxaminecarbinoxamine and amitriptyline both increase sedation. Use Caution/Monitor.carisoprodolcarisoprodol and amitriptyline both increase sedation. Use Caution/Monitor.carisoprodol and perphenazine both increase sedation. Use Caution/Monitor.carvedilolperphenazine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.cenobamatecenobamate, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.cenobamatecenobamate, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor.ceritinibceritinib and perphenazine both increase QTc interval. Use Caution/Monitor.ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.cevimelinecevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.chloral hydratechloral hydrate and perphenazine both increase sedation. Use Caution/Monitor.chloral hydratechloral hydrate and amitriptyline both increase sedation. Use Caution/Monitor.chlordiazepoxidechlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.chloroquinechloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.chlorpheniraminechlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.chlorpheniraminechlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.chlorpromazinechlorpromazine and perphenazine both increase sedation. Use Caution/Monitor.chlorpromazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.chlorpromazine and amitriptyline both increase sedation. Use Caution/Monitor.chlorzoxazonechlorzoxazone and perphenazine both increase sedation. Use Caution/Monitor.chlorzoxazone and amitriptyline both increase sedation. Use Caution/Monitor.cigarette smokingcigarette smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.cimetidinecimetidine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cinnarizinecinnarizine and amitriptyline both increase sedation. Use Caution/Monitor.cinnarizine and perphenazine both increase sedation. Use Caution/Monitor.cisatracuriumcisatracurium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.cisatracurium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.perphenazine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.citalopramcitalopram and perphenazine both increase QTc interval. Use Caution/Monitor.clarithromycinclarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.clemastineclemastine and amitriptyline both increase sedation. Use Caution/Monitor.clemastine and perphenazine both increase sedation. Use Caution/Monitor.clobazamamitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. clobazam will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. clomipramineamitriptyline and clomipramine both increase sedation. Use Caution/Monitor.perphenazine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.amitriptyline and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.perphenazine and clomipramine both increase sedation. Use Caution/Monitor.clonazepamclonazepam and perphenazine both increase sedation. Use Caution/Monitor.clonazepam and amitriptyline both increase sedation. Use Caution/Monitor.clonidineclonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.clorazepateclorazepate and amitriptyline both increase sedation. Use Caution/Monitor.clorazepateclorazepate and perphenazine both increase sedation. Use Caution/Monitor.clotrimazoleclotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.clozapineclozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.clozapine and amitriptyline both increase sedation. Use Caution/Monitor.clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.clozapine and perphenazine both increase sedation. Use Caution/Monitor.cobicistatcobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration. cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat. cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant responsecocaine topicalamitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeinecodeine and perphenazine both increase sedation. Use Caution/Monitor.codeinecodeine and amitriptyline both increase sedation. Use Caution/Monitor.conivaptanconivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.crizotinibcrizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.cyclizinecyclizine and amitriptyline both increase sedation. Use Caution/Monitor.cyclizine and perphenazine both increase sedation. Use Caution/Monitor.cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.cyclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.cyclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.cyclobenzaprinecyclobenzaprine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.cyclobenzaprine and perphenazine both increase sedation. Use Caution/Monitor.perphenazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.cyclobenzaprine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.cyclobenzaprine and amitriptyline both increase sedation. Use Caution/Monitor.cyclosporinecyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.cyproheptadinecyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.cyproheptadinecyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor.dantrolenedantrolene and perphenazine both increase sedation. Use Caution/Monitor.dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.daridorexantperphenazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. amitriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. darifenacindarifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.darifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.perphenazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.darifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.darunavirdarunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.dasatinibperphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.dasatinibamitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.debrisoquineamitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.degarelixdegarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.desfluranedesflurane and amitriptyline both increase sedation. Use Caution/Monitor.desflurane and perphenazine both increase QTc interval. Use Caution/Monitor.desflurane and perphenazine both increase sedation. Use Caution/Monitor.desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.desipramineamitriptyline and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.perphenazine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.perphenazine and desipramine both increase sedation. Use Caution/Monitor.amitriptyline and desipramine both increase sedation. Use Caution/Monitor.desvenlafaxinedesvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgdeutetrabenazineamitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration