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 topicalMonitor Closely (1)amitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineMonitor Closely (2)codeine and perphenazine both increase sedation. Use Caution/Monitor. codeine and amitriptyline 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.conivaptanMonitor Closely (1)conivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.conjugated estrogensMinor (1)conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.conjugated estrogens, vaginalMinor (1)conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.cortisoneMinor (1)cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.crizotinibMonitor Closely (2)crizotinib 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.cyclizineMonitor Closely (6)cyclizine 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.cyclobenzaprineMonitor Closely (5)cyclobenzaprine 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.Serious - Use Alternative (1)amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyclosporineMonitor Closely (2)cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cyproheptadineMonitor Closely (2)cyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor. cyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.dacomitinibSerious - Use Alternative (2)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. dacomitinib will increase the level or effect of amitriptyline 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 (2)dantrolene and perphenazine both increase sedation. Use Caution/Monitor. dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (2)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. 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. darifenacinMonitor Closely (5)darifenacin 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.Minor (1)darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.darunavirMonitor Closely (1)darunavir 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.dasatinibMonitor Closely (2)amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.debrisoquineMonitor Closely (1)amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.degarelixMonitor Closely (1)degarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)degarelix and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.desfluraneMonitor Closely (4)desflurane 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.Minor (1)desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.desipramineMonitor Closely (4)amitriptyline 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.Serious - Use Alternative (3)perphenazine and desipramine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and desipramine both increase serotonin levels. 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 mgSerious - Use Alternative (1)amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.deutetrabenazineMonitor Closely (5)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. amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor. perphenazine and deutetrabenazine both increase sedation. Use Caution/Monitor. 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). 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 with other drugs that prolong QTc interval, presence of congenital QT prolongation).dexamethasoneMinor (1)dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dexchlorpheniramineMonitor Closely (2)dexchlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor. dexchlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.dexfenfluramineMonitor Closely (4)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. amitriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely. perphenazine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dexfenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dexmedetomidineMonitor Closely (2)dexmedetomidine and perphenazine both increase sedation. Use Caution/Monitor. dexmedetomidine and amitriptyline both increase sedation. Use Caution/Monitor.dexmethylphenidateMonitor Closely (3)perphenazine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. 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.Serious - Use Alternative (1)amitriptyline, dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.dextroamphetamineMonitor Closely (5)amitriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely. amitriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. 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. amitriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor. perphenazine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dextroamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextroamphetamine transdermalMonitor Closely (2)amitriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response. 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).Serious - Use Alternative (1)amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.dextromoramideMonitor Closely (2)dextromoramide and perphenazine both increase sedation. Use Caution/Monitor. dextromoramide and amitriptyline both increase sedation. Use Caution/Monitor.DHEA, herbalMinor (1)DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.diamorphineMonitor Closely (2)diamorphine and perphenazine both increase sedation. Use Caution/Monitor. diamorphine and amitriptyline both increase sedation. Use Caution/Monitor.diazepamMonitor Closely (2)diazepam and perphenazine both increase sedation. Use Caution/Monitor. diazepam and amitriptyline both increase sedation. Use Caution/Monitor.diazepam intranasalMonitor Closely (1)diazepam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.dicyclomineMonitor Closely (4)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. dicyclomine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.diethylpropionMonitor Closely (3)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