of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.midazolamMonitor Closely (2)midazolam and perphenazine both increase sedation. Use Caution/Monitor. midazolam and amitriptyline both increase sedation. Use Caution/Monitor.midazolam intranasalMonitor Closely (2)midazolam intranasal, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. midazolam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.midodrineMonitor Closely (3)perphenazine, midodrine. 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 midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, midodrine. 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.mifepristoneMonitor Closely (2)mifepristone, perphenazine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available. mifepristone, amitriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.miglitolMinor (1)amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.milnacipranMonitor Closely (1)milnacipran, 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)milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.mipomersenMonitor Closely (1)mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.mirabegronMonitor Closely (2)mirabegron will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.mirtazapineMonitor Closely (4)perphenazine and mirtazapine both increase sedation. Use Caution/Monitor. amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. amitriptyline and mirtazapine both increase sedation. Use Caution/Monitor. mirtazapine and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.mobocertinibSerious - Use Alternative (2)mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently mobocertinib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.modafinilMonitor Closely (3)perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.moexiprilMinor (1)perphenazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.morphineMonitor Closely (4)perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. morphine and perphenazine both increase sedation. Use Caution/Monitor. morphine and amitriptyline both increase sedation. Use Caution/Monitor.motherwortMonitor Closely (2)perphenazine and motherwort both increase sedation. Use Caution/Monitor. amitriptyline and motherwort both increase sedation. Use Caution/Monitor.moxifloxacinSerious - Use Alternative (2)perphenazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.moxonidineMonitor Closely (2)perphenazine and moxonidine both increase sedation. Use Caution/Monitor. amitriptyline and moxonidine both increase sedation. Use Caution/Monitor.nabiloneMonitor Closely (2)perphenazine and nabilone both increase sedation. Use Caution/Monitor. amitriptyline and nabilone both increase sedation. Use Caution/Monitor.nalbuphineMonitor Closely (2)nalbuphine and amitriptyline both increase sedation. Use Caution/Monitor. nalbuphine and perphenazine both increase sedation. Use Caution/Monitor.naratriptanMonitor Closely (2)naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely. naratriptan, 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).nateglinideMinor (1)amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.nebivololMonitor Closely (1)perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.nefazodoneMonitor Closely (2)nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.nefopamMonitor Closely (1)nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.nelfinavirMonitor Closely (1)nelfinavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.neostigmineMonitor Closely (1)neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.netupitant/palonosetronSerious - Use Alternative (1)netupitant/palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.nevirapineMinor (1)nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nicardipineMonitor Closely (1)nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.nifedipineMonitor Closely (1)nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.nilotinibSerious - Use Alternative (2)perphenazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.norepinephrineMonitor Closely (4)amitriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. perphenazine, norepinephrine. 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 norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, norepinephrine. 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.nortriptylineMonitor Closely (4)amitriptyline and nortriptyline both increase sedation. Use Caution/Monitor. perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug. amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.octreotideSerious - Use Alternative (2)perphenazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.octreotide (Antidote)Serious - Use Alternative (2)amitriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug. perphenazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.ofloxacinMonitor Closely (2)amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.olanzapineMonitor Closely (5)olanzapine and perphenazine both increase sedation. Use Caution/Monitor. olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor. olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. olanzapine and amitriptyline both increase sedation. Use Caution/Monitor. olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor.oliceridineMonitor Closely (3)amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. oliceridine, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. 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. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics). amitriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.olodaterol inhaledMonitor Closely (2)amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias perphenazine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmiasolopatadine intranasalSerious - Use Alternative (2)perphenazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. amitriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. onabotulinumtoxinAMonitor Closely (4)onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. onabotulinumtoxinA decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. onabotulinumtoxinA decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.ondansetronSerious - Use Alternative (3)perphenazine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias. amitriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias. ondansetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.opium tinctureMonitor Closely (2)opium tincture and perphenazine both increase sedation. Use Caution/Monitor. opium tincture and amitriptyline both increase sedation. Use Caution/Monitor.orphenadrineMonitor Closely (3)amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor. orphenadrine and perphenazine both increase sedation. Use Caution/Monitor. orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.osilodrostatMonitor Closely (1)osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.osimertinibMonitor Closely (2)osimertinib and perphenazine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval. osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.oxaliplatinMonitor Closely (2)oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval. oxaliplatin and perphenazine both increase QTc interval. Use Caution/Monitor.oxazepamMonitor Closely (2)oxazepam and perphenazine both increase sedation. Use Caution/Monitor. oxazepam and amitriptyline both increase sedation. Use Caution/Monitor.oxcarbazepineMinor (2)oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown. oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.oxybutyninMonitor Closely (4)oxybutynin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. oxybutynin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. perphenazine