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).ergotamineMonitor Closely (2)ergotamine, 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 ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.eribulinMonitor Closely (2)eribulin and amitriptyline both increase QTc interval. Use Caution/Monitor. eribulin and perphenazine both increase QTc interval. Use Caution/Monitor.erythromycin baseSerious - Use Alternative (4)amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug. erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. erythromycin base will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. perphenazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.erythromycin ethylsuccinateSerious - Use Alternative (4)erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. erythromycin ethylsuccinate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. perphenazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.erythromycin lactobionateSerious - Use Alternative (4)erythromycin lactobionate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. perphenazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.erythromycin stearateSerious - Use Alternative (4)erythromycin stearate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. perphenazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.escitalopramMonitor Closely (1)escitalopram increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.esketamine intranasalMonitor Closely (1)esketamine intranasal, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.eslicarbazepine acetateMonitor Closely (1)eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.esomeprazoleMonitor Closely (1)esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.estazolamMonitor Closely (2)estazolam and amitriptyline both increase sedation. Use Caution/Monitor. estazolam and perphenazine both increase sedation. Use Caution/Monitor.estradiolMinor (1)estradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.estrogens conjugated syntheticMinor (1)estrogens conjugated synthetic, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.estrogens esterifiedMinor (1)estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.estropipateMinor (1)estropipate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.ethanolMonitor Closely (2)perphenazine and ethanol both increase sedation. Use Caution/Monitor. amitriptyline and ethanol both increase sedation. Use Caution/Monitor.Minor (2)ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills. ethanol, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.ethinylestradiolMinor (1)ethinylestradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.etomidateMonitor Closely (2)etomidate and amitriptyline both increase sedation. Use Caution/Monitor. etomidate and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.etravirineMonitor Closely (1)etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.eucalyptusMinor (2)amitriptyline and eucalyptus both increase sedation. Minor/Significance Unknown. perphenazine and eucalyptus both increase sedation. Minor/Significance Unknown.ezogabineMonitor Closely (1)ezogabine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.fedratinibMonitor Closely (2)fedratinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary. fedratinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.felbamateMonitor Closely (1)felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.felodipineMonitor Closely (1)felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.fenfluramineMonitor Closely (5)perphenazine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely. perphenazine, fenfluramine. 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. fenfluramine, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.Serious - Use Alternative (1)amitriptyline, fenfluramine. 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.fentanylMonitor Closely (1)fentanyl, 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)fentanyl, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl intranasalSerious - Use Alternative (1)fentanyl intranasal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl transdermalSerious - Use Alternative (1)fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fentanyl transmucosalSerious - Use Alternative (1)fentanyl transmucosal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.fesoterodineMonitor Closely (4)fesoterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. perphenazine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. fesoterodine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. fesoterodine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (1)perphenazine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.fexinidazoleSerious - Use Alternative (1)fexinidazole and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.fezolinetantContraindicated (2)perphenazine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors amitriptyline will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitorsfingolimodMonitor Closely (2)fingolimod and perphenazine both increase QTc interval. Use Caution/Monitor. fingolimod and amitriptyline both increase QTc interval. Use Caution/Monitor.flavoxateMonitor Closely (4)perphenazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. flavoxate decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. flavoxate decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.flecainideMonitor Closely (3)amitriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. perphenazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.flibanserinMonitor Closely (1)flibanserin, perphenazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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).fluconazoleMonitor Closely (2)fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. fluconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug. perphenazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.fludrocortisoneMinor (1)fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.fluoxetineMonitor Closely (1)amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (5)fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug. perphenazine and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug. fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. perphenazine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. fluoxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.fluphenazineMonitor Closely (3)fluphenazine and perphenazine both increase sedation. Use Caution/Monitor. fluphenazine and amitriptyline both increase sedation. Use Caution/Monitor. fluphenazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (2)fluphenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. fluphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)amitriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. amitriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects. perphenazine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.flurazepamMonitor Closely (2)flurazepam and perphenazine both