Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated amitriptyline increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated. perphenazine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.vilazodoneMonitor Closely (1)vilazodone, 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, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .vildagliptinMinor (1)amitriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.voclosporinMonitor Closely (1)voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (3)perphenazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely. voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)voriconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.vorinostatMonitor Closely (1)vorinostat and perphenazine both increase QTc interval. Use Caution/Monitor.vortioxetineSerious - Use Alternative (1)amitriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.warfarinMonitor Closely (1)amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.xylometazolineMonitor Closely (3)perphenazine, xylometazoline. 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 xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, xylometazoline. 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.yohimbeSerious - Use Alternative (2)yohimbe, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure. yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.yohimbineMonitor Closely (3)amitriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. perphenazine, yohimbine. 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 yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, yohimbine. 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.zafirlukastMinor (1)zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ziconotideMonitor Closely (2)amitriptyline and ziconotide both increase sedation. Use Caution/Monitor. perphenazine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (3)ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor. perphenazine and ziprasidone both increase sedation. Use Caution/Monitor. perphenazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (2)zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely. zolmitriptan, 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).zolpidemMonitor Closely (1)perphenazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performanceMinor (1)zolpidem, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.zotepineMonitor Closely (2)perphenazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. perphenazine and zotepine both increase sedation. Use Caution/Monitor. Frequency Not Defined Sedation Fatigue Constipation Dry mouth Lethargy Weakness Anticholinergic effects Blurred vision Lens opacities Orthostatic hypotension Agitation Anxiety Headache Insomnia Nausea/vomiting Sweating Orthostatic hypotension ECG changes Tachycardia Confusion EPS Dizziness Paresthesia Rash Increased LFTs Sexual dysfunction Tinnitus Seizure Agranulocytosis Thrombocytopenia Eosinophilia Leukopenia SIADH Antipsychotic side effects Poikilothermia Decreased gag reflex Weight gain Amenorrhea Post Marketing Reports Neuroleptic malignant syndrome Serotonin syndrome Black Box Warnings Children & Antidepressants In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (< 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses. This increase was not seen in patients >24 years of age. A slight decrease in suicidal thinking was seen in adults >65 years. Risks must be weighed in children and young adults against the benefits of taking antidepressants. Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies. This should be done during the initial 1-2 months of therapy and dosage adjustments. The patient’s family should communicate to the healthcare provider any abrupt changes in behavior. Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy. This drug is not approved for use in pediatric patients. Antipsychotics & Dementia Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. This drug is not approved for the treatment of patients with dementia-related psychosis (See WARNINGS in package insert). Contraindications Tricyclic Antidepressant (amitriptyline): hypersensitivity, severe cardiovascular disorder, narrow angle glaucoma, within 14 days of MAOIs (risk of serotonin syndrome), any drugs or conditions that prolong QT interval, acute recovery post-MI Antipsychotic (perphenazine): hypersensitivity, CNS depression, neuroleptic malignant syndrome, poorly controlled seizure disorder, subcortical braine damage, coma, severe obtundation, high dose CNS depressants, blood dyscrasia, myelosuppression, liver damage Pregnancy Category: D Lactation: excreted in breast milk; not recommendedPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects Perphenazine: Antipsychotic agent; elicits moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity Pharmacokinetics Amitriptyline Onset of action: 6 weeks Half-life: 9-27 hr Peak serum time: 4 hr Metabolism: Hepatic (CYP2C19, CYP3A4) Excretion: Urine (25-50%); bile (small amounts) Perphenazine Half-life: 9-12 hr Peak plasma time: 1-3 hr; 2-4 hr (metabolite) Metabolism: Hepatic P450 enzyme (CYP2D6) Excretion: Urine; feces No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. QL Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. ST Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. Plans Select State: Alabama Alaska Arizona Arkansas California Colorado Connecticut Delaware District of Columbia Florida Georgia Hawaii Idaho Illinois Indiana Iowa Kansas Kentucky Louisiana Maine Maryland Massachusetts Michigan Minnesota Mississippi Missouri Montana Nebraska Nevada New Hampshire New Jersey New Mexico New York North Carolina North Dakota Ohio Oklahoma Oregon Pennsylvania Puerto Rico Rhode Island South Carolina South Dakota Tennessee Texas Utah Vermont Virginia Washington West Virginia Wisconsin Wyoming Done Non-Medicare Plans Medicare Plans Done CLOSE Additional Offers CLOSE Email to Patient From: To: The recipient will receive more details and instructions to access this offer. By clicking send, you acknowledge that you have permission to email the recipient with this information. 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