of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, diethylpropion. 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.difelikefalinMonitor Closely (2)difelikefalin and perphenazine both increase sedation. Use Caution/Monitor. difelikefalin and amitriptyline both increase sedation. Use Caution/Monitor.difenoxin hclMonitor Closely (2)difenoxin hcl and perphenazine both increase sedation. Use Caution/Monitor. difenoxin hcl and amitriptyline both increase sedation. Use Caution/Monitor.dihydroergotamineMonitor Closely (2)dihydroergotamine, 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). amitriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalMonitor Closely (1)amitriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.diltiazemMonitor Closely (1)diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.dimenhydrinateMonitor Closely (2)dimenhydrinate and amitriptyline both increase sedation. Use Caution/Monitor. dimenhydrinate and perphenazine both increase sedation. Use Caution/Monitor.diphenhydramineMonitor Closely (6)perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor. diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.diphenoxylate hclMonitor Closely (2)diphenoxylate hcl and perphenazine both increase sedation. Use Caution/Monitor. diphenoxylate hcl and amitriptyline both increase sedation. Use Caution/Monitor.dipipanoneMonitor Closely (2)dipipanone and perphenazine both increase sedation. Use Caution/Monitor. dipipanone and amitriptyline both increase sedation. Use Caution/Monitor.disopyramideContraindicated (2)amitriptyline and disopyramide both increase QTc interval. Contraindicated. perphenazine and disopyramide both increase QTc interval. Contraindicated.dobutamineMonitor Closely (3)perphenazine, dobutamine. 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 dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dobutamine. 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.dofetilideMonitor Closely (2)dofetilide increases toxicity of perphenazine by QTc interval. Use Caution/Monitor. dofetilide increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.dolasetronMonitor Closely (2)perphenazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely. amitriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dolasetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.donepezilMonitor Closely (3)donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor. donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely. donepezil and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.donepezil transdermalMonitor Closely (1)donepezil transdermal, perphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.dopamineMonitor Closely (3)perphenazine, dopamine. 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 dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated. amitriptyline, dopamine. 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.dopexamineMonitor Closely (2)perphenazine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dopexamine. 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.dosulepinMonitor Closely (3)amitriptyline and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor. perphenazine and dosulepin both increase sedation. Use Caution/Monitor. amitriptyline and dosulepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and dosulepin both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.doxepinMonitor Closely (3)perphenazine and doxepin both increase sedation. Use Caution/Monitor. amitriptyline and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor. amitriptyline and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug. perphenazine and doxepin both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and doxepin both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)doxepin, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. doxepin, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. perphenazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.doxylamineMonitor Closely (2)doxylamine and amitriptyline both increase sedation. Use Caution/Monitor. doxylamine and perphenazine both increase sedation. Use Caution/Monitor.dronedaroneContraindicated (2)dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.Serious - Use Alternative (3)dronedarone and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. perphenazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)dronedarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.droperidolMonitor Closely (3)droperidol and perphenazine both increase sedation. Use Caution/Monitor. droperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. droperidol and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.duloxetineMonitor Closely (1)perphenazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.echothiophate iodideMonitor Closely (1)echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.efavirenzMonitor Closely (4)efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor. efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. efavirenz and perphenazine both increase QTc interval. Use Caution/Monitor. efavirenz will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.elagolixMonitor Closely (1)elagolix will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.eletriptanMonitor Closely (2)eletriptan, 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). eletriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.eliglustatMonitor Closely (5)eliglustat and perphenazine both increase QTc interval. Use Caution/Monitor. eliglustat and amitriptyline both increase QTc interval. Use Caution/Monitor. eliglustat increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect. eliglustat increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect. eliglustat increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.elvitegravir/cobicistat/emtricitabine/tenofovir DFMonitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; A decrease in dose of the neuroleptic may be needed when coadministered. elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.enalaprilMinor (1)perphenazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.encainideMinor (1)perphenazine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.encorafenibMonitor Closely (1)encorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)encorafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.entrectinibMonitor Closely (2)entrectinib and amitriptyline both increase QTc interval. Use Caution/Monitor. entrectinib and perphenazine both increase QTc interval. Use Caution/Monitor.ephedrineMonitor Closely (4)perphenazine, ephedrine. 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 ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor. amitriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, ephedrine. 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.epinephrineMonitor Closely (5)amitriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor. perphenazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia. perphenazine, epinephrine. 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 epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (3)epinephrine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. epinephrine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline, epinephrine. 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.epinephrine inhaledMonitor Closely (1)amitriptyline and epinephrine inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Tricyclic antidepressants may potentiate epinephrine effect on cardiovascular system.epinephrine racemicMonitor Closely (4)perphenazine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia. amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor. perphenazine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (3)epinephrine racemic and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. epinephrine racemic and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline, epinephrine racemic. 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.ergoloid mesylatesMonitor Closely (1)ergoloid mesylates, perphenazine. unspecified