may be necessarytacrolimusMonitor Closely (1)tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.tapentadolMonitor Closely (2)amitriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely. tapentadol and amitriptyline both increase sedation. Use Caution/Monitor.tedizolidSerious - Use Alternative (1)tedizolid, amitriptyline. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.telavancinMonitor Closely (1)amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.temazepamMonitor Closely (1)temazepam and amitriptyline both increase sedation. Use Caution/Monitor.terbinafineMonitor Closely (1)terbinafine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.terbutalineMonitor Closely (1)amitriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, terbutaline. 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.teriflunomideMonitor Closely (1)teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tetrabenazineMonitor Closely (1)tetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.thioridazineMonitor Closely (1)thioridazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. amitriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.thiothixeneMonitor Closely (1)thiothixene and amitriptyline both increase sedation. Use Caution/Monitor.thyroid desiccatedMonitor Closely (1)thyroid desiccated increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.tiotropiumMonitor Closely (1)tiotropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.tolazamideMinor (1)amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.tolbutamideMinor (1)amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.tolterodineMonitor Closely (1)tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.tolvaptanMonitor Closely (1)tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.topiramateMonitor Closely (2)topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels. amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.toremifeneSerious - Use Alternative (1)amitriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.tramadolMonitor Closely (2)amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely. tramadol and amitriptyline both increase sedation. Use Caution/Monitor.tranylcypromineContraindicated (1)tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.trazodoneMonitor Closely (3)trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor. amitriptyline and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug. trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.triazolamMonitor Closely (1)triazolam and amitriptyline both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and amitriptyline both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trifluoperazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. amitriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.trihexyphenidylMonitor Closely (1)trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.trimethoprimMonitor Closely (1)amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.trimipramineMonitor Closely (2)amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. amitriptyline and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.triprolidineMonitor Closely (1)triprolidine and amitriptyline both increase sedation. Use Caution/Monitor.tropisetronMonitor Closely (1)amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.trospium chlorideMonitor Closely (1)trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.tucatinibMonitor Closely (1)tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.umeclidinium bromide/vilanterol inhaledSerious - Use Alternative (2)amitriptyline increases toxicity of umeclidinium bromide/vilanterol 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. amitriptyline and umeclidinium bromide/vilanterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or 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 potentiatedvalbenazineMonitor Closely (1)valbenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.valerianMonitor Closely (1)valerian and amitriptyline both increase sedation. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)amitriptyline, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.vasopressinMinor (1)amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.vecuroniumMonitor Closely (1)vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.vemurafenibSerious - Use Alternative (1)vemurafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.venlafaxineMonitor Closely (1)amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)venlafaxine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.verapamilMonitor Closely (1)verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive. Minor (2)verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (2)amitriptyline and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or 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.vilazodoneSerious - 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 (2)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.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 (1)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 (1)yohimbe, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.yohimbineMonitor Closely (1)amitriptyline 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 (1)amitriptyline and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.zolpidemMinor (1)zolpidem, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression. Frequency Not Defined Agitation Agranulocytosis Alopecia Anxiety Anorexia Ataxia Arrhythmia Blurred vision Coma Confusion Constipation Diarrhea Dizziness Dry mouth ECG changes Eosinophilia Extrapyramidal symptoms (EPS) Fatigue Hallucination Headache Hypertension Increased LFTs Insomnia Lethargy Leukopenia MI Nausea Ocular pressure increased Orthostatic hypotension Palpitation Paresthesia Photosensitivity Rash Restlessness Sedation Seizure Sexual dysfunction SIADH Stroke Stomatitis Syncope Sweating Tachycardia Thrombocytopenia Tinnitus Urinary retention Urticaria Vomiting Xerostomia Weakness Weight gain Black Box Warnings In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients over age 24 years; a slight decrease in suicidal thinking was seen in adults over age 65 years In children and young adults, the risks must be weighed 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 any abrupt changes in behavior to the healthcare provider 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 <12 years Not FDA approved for treatment of bipolar depressionContraindications Hypersensitivity Acute recovery phase following MI Concurrent use with cisapride Contraindicated within 14 days of MAOIs; if linezolid or IV methylene blue (MAOIs) must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring, whichever comes first Cautions Bone marrow suppression reported Avoid use in narrow-angle glaucoma May cause sedation and impair mental and physical abilities Avoid use with any drugs or conditions that prolong QT interval May cause orthostatic hypotension Use caution in patients with cardiovascular disease, diabetes, mania, hepatic and renal impairment, thyroid dysfunction, and seizure disorder May worsen mania symptoms or precipitate mania in patients with bipolar disorder Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (18-24 years) Risk of anticholinergic side effects; may cause constipation, urinary retention, blurred vision, and xerostomia Use caution in patients with urinary retention, open-angle glaucoma, BPH, decreased gastrointestinal motility, or paralytic ileus Possibility of EPS and neuroleptic malignant syndrome Abrupt discontinuation of therapy not recommended in patients receiving high doses for prolonged periods Fractures reported with therapy Pregnancy category: C Lactation: Distributed in breast milk; do not nurse (AAP states effect on nursing infants is unknown but may be of concern)Pregnancy 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 Neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; anticholinergic Absorption Peak serum time: 4 hr Metabolism Metabolized by hepatic CYP2C19, CYP3A4 Metabolites: Nortriptyline Elimination Half-life: 9-27 hr Excretion: Urine (18%), small