by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .brexanoloneMonitor Closely (1)brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.brexpiprazoleMonitor Closely (1)brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.brimonidineMonitor Closely (1)brimonidine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.brivaracetamMonitor Closely (1)brivaracetam and perphenazine both increase sedation. Use Caution/Monitor.bromocriptineSerious - Use Alternative (1)perphenazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.brompheniramineMonitor Closely (1)brompheniramine and perphenazine both increase sedation. Use Caution/Monitor.buprenorphineMonitor Closely (2)buprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor. buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine buccalMonitor Closely (2)buprenorphine buccal and perphenazine both increase QTc interval. Use Caution/Monitor. buprenorphine buccal and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine subdermal implantMonitor Closely (2)buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor. buprenorphine subdermal implant and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine transdermalMonitor Closely (2)buprenorphine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor. buprenorphine transdermal and perphenazine both increase sedation. Use Caution/Monitor.buprenorphine, long-acting injectionMonitor Closely (3)perphenazine 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.bupropionMonitor Closely (2)perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible. bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.butabarbitalMonitor Closely (1)butabarbital and perphenazine both increase sedation. Use Caution/Monitor.butalbitalMonitor Closely (1)butalbital and perphenazine both increase sedation. Use Caution/Monitor.butorphanolMonitor Closely (1)butorphanol and perphenazine both increase sedation. Use Caution/Monitor.cabergolineSerious - Use Alternative (1)perphenazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.caffeineMonitor Closely (1)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.calcium/magnesium/potassium/sodium oxybatesSerious - Use Alternative (1)perphenazine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.captoprilMinor (1)perphenazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.carbinoxamineMonitor Closely (1)carbinoxamine and perphenazine both increase sedation. Use Caution/Monitor.carisoprodolMonitor Closely (1)carisoprodol and perphenazine both increase sedation. Use Caution/Monitor.carvedilolMonitor Closely (1)perphenazine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.celecoxibMinor (1)celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.cenobamateMonitor Closely (1)cenobamate, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor.ceritinibMonitor Closely (1)ceritinib and perphenazine both increase QTc interval. Use Caution/Monitor.chasteberryMinor (1)chasteberry decreases effects of perphenazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).chloral hydrateMonitor Closely (1)chloral hydrate and perphenazine both increase sedation. Use Caution/Monitor.chlordiazepoxideMonitor Closely (1)chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.chloroquineMinor (3)chloroquine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. chloroquine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown. chloroquine increases toxicity of perphenazine by QTc interval. Minor/Significance Unknown.chlorpheniramineMonitor Closely (1)chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.chlorpromazineMonitor Closely (2)chlorpromazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. chlorpromazine and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.chlorzoxazoneMonitor Closely (1)chlorzoxazone and perphenazine both increase sedation. Use Caution/Monitor.cigarette smokingMonitor Closely (1)cigarette smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.cimetidineMinor (1)cimetidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.cinnarizineMonitor Closely (1)cinnarizine and perphenazine both increase sedation. Use Caution/Monitor.cisatracuriumMonitor Closely (3)cisatracurium 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.citalopramMonitor Closely (1)citalopram and perphenazine both increase QTc interval. Use Caution/Monitor.clarithromycinSerious - Use Alternative (1)perphenazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.clemastineMonitor Closely (1)clemastine and perphenazine both increase sedation. Use Caution/Monitor.clobazamMonitor Closely (1)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. clomipramineMonitor Closely (2)perphenazine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. perphenazine and clomipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)clomipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. clomipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.clonazepamMonitor Closely (1)clonazepam and perphenazine both increase sedation. Use Caution/Monitor.clonidineMonitor Closely (1)clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.clorazepateMonitor Closely (1)clorazepate and perphenazine both increase sedation. Use Caution/Monitor.clozapineMonitor Closely (3)clozapine and perphenazine both increase QTc interval. Use Caution/Monitor. clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. clozapine and perphenazine both increase sedation. Use Caution/Monitor.cobicistatMonitor Closely (1)cobicistat 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. codeineMonitor Closely (1)codeine and perphenazine both increase sedation. Use Caution/Monitor.Minor (2)perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.crizotinibMonitor Closely (1)crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.cyclizineMonitor Closely (4)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. perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. cyclizine and perphenazine both increase sedation. Use Caution/Monitor.cyclobenzaprineMonitor Closely (4)cyclobenzaprine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. cyclobenzaprine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. cyclobenzaprine and perphenazine both increase sedation. Use Caution/Monitor.cyproheptadineMonitor Closely (1)cyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.dacomitinibSerious - Use Alternative (1)dacomitinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities. dantroleneMonitor Closely (1)dantrolene and perphenazine both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (1)perphenazine 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. darifenacinMonitor Closely (3)darifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. darifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dasatinibMonitor Closely (1)perphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.degarelixSerious - Use Alternative (1)degarelix and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.desfluraneMonitor Closely (2)desflurane and perphenazine both increase QTc interval. Use Caution/Monitor. desflurane and perphenazine both increase sedation. Use Caution/Monitor.desipramineMonitor Closely (2)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.Serious - Use Alternative (1)perphenazine and desipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)desipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. desipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.desvenlafaxineMonitor Closely (1)desvenlafaxine 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 mgdeutetrabenazineMonitor Closely (3)perphenazine and deutetrabenazine both increase sedation. Use Caution/Monitor. perphenazine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics. deutetrabenazine and perphenazine 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 with other drugs that prolong QTc interval, presence of congenital QT prolongation).dexchlorpheniramineMonitor Closely (1)dexchlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.dexfenfluramineMonitor Closely (2)perphenazine, dexfenfluramine. 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 dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dexmedetomidineMonitor Closely (1)dexmedetomidine and perphenazine both increase sedation. Use Caution/Monitor.dexmethylphenidateMonitor Closely (2)perphenazine, dexmethylphenidate. 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 dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.dextroamphetamineMonitor Closely (2)perphenazine, dextroamphetamine. 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 dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextroamphetamine transdermalMonitor Closely (1)perphenazine, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).dextromethorphanMonitor Closely (1)dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextromoramideMonitor Closely (1)dextromoramide and perphenazine both increase sedation. Use Caution/Monitor.diamorphineMonitor Closely (1)diamorphine and perphenazine both increase sedation. Use Caution/Monitor.diazepamMonitor Closely (1)diazepam and perphenazine both increase sedation. Use Caution/Monitor.dicyclomineMonitor Closely (3)dicyclomine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. dicyclomine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.diethylpropionMonitor Closely (2)perphenazine, diethylpropion. 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 diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.difelikefalinMonitor Closely (1)difelikefalin and perphenazine both increase sedation. Use Caution/Monitor.difenoxin hclMonitor Closely (1)difenoxin