by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.tedizolidSerious - Use Alternative (1)tedizolid, mirtazapine. 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)mirtazapine and telavancin both increase QTc interval. Use Caution/Monitor.temazepamMonitor Closely (1)temazepam and mirtazapine both increase sedation. Use Caution/Monitor.terbinafineMonitor Closely (1)terbinafine will increase the level or effect of mirtazapine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.terbutalineMonitor Closely (1)mirtazapine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.teriflunomideMonitor Closely (1)teriflunomide decreases levels of mirtazapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tetrabenazineSerious - Use Alternative (1)mirtazapine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.thioridazineContraindicated (1)mirtazapine and thioridazine both increase QTc interval. Contraindicated.Monitor Closely (1)thioridazine and mirtazapine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)thiothixene and mirtazapine both increase sedation. Use Caution/Monitor.tinidazoleMonitor Closely (1)mirtazapine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.topiramateMonitor Closely (1)mirtazapine and topiramate both increase sedation. Modify Therapy/Monitor Closely.toremifeneSerious - Use Alternative (1)mirtazapine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.tramadolMonitor Closely (2)tramadol and mirtazapine both increase sedation. Use Caution/Monitor. mirtazapine and tramadol both increase serotonin levels. Use Caution/Monitor.tranylcypromineSerious - Use Alternative (1)tranylcypromine and mirtazapine both increase serotonin levels. Avoid or Use Alternate Drug.trazodoneMonitor Closely (2)trazodone and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. trazodone and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.triazolamMonitor Closely (1)triazolam and mirtazapine both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)mirtazapine and triclabendazole both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and mirtazapine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (2)trifluoperazine and mirtazapine both increase sedation. Use Caution/Monitor. mirtazapine and trifluoperazine both decrease QTc interval. Use Caution/Monitor.trimipramineMonitor Closely (2)trimipramine and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. trimipramine and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.triprolidineMonitor Closely (1)triprolidine and mirtazapine both increase sedation. Use Caution/Monitor.triptorelinMonitor Closely (1)mirtazapine and triptorelin both increase QTc interval. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valbenazineMonitor Closely (1)valbenazine and mirtazapine both increase QTc interval. Use Caution/Monitor.vandetanibSerious - Use Alternative (1)mirtazapine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.vardenafilMonitor Closely (1)mirtazapine and vardenafil both increase QTc interval. Use Caution/Monitor.vemurafenibSerious - Use Alternative (1)mirtazapine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.venlafaxineMonitor Closely (1)venlafaxine and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)mirtazapine and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.vilazodoneSerious - Use Alternative (1)mirtazapine, 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. .voclosporinMonitor Closely (1)mirtazapine and voclosporin both increase QTc interval. Use Caution/Monitor.voriconazoleContraindicated (2)voriconazole will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. mirtazapine and voriconazole both increase QTc interval. Contraindicated.vorinostatMonitor Closely (1)mirtazapine and vorinostat both increase QTc interval. Use Caution/Monitor.vortioxetineSerious - Use Alternative (1)mirtazapine, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)mirtazapine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)mirtazapine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)mirtazapine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan and mirtazapine both increase serotonin levels. Use Caution/Monitor. >10% Somnolence (54%) Weight gain (>7% increase in <49% of pediatric patients) Xerostomia (25%) Increased appetite (17%) Constipation (13%) 1-10% Asthenia (8%) Weakness (8%) Weight gain (>7% increase in 8% of adults) Dizziness (7%) Serum TGs increased (6%) Dream disorder (4%) Disturbance in thinking (3%) ALT increased (2%) Peripheral edema (2%) Myalgia (2%) Confusion (2%) Urinary frequency (2%) Tremor (2%) Back pain (2%) Dyspnea (1%) <1% Mania (0.2%) Grand mal seizure (less than 0.1%) Frequency Not Defined Depression exacerbation Status epilepticus Suicidal thoughts, suicide (rare) Agranulocytosis Neutropenia Postmarketing Reports Arrythmia Torsades de Pointes Hyperprolactenemia and related symptoms galactorrhea and gynecomastia Sonambulism (complex behaviors) Severe skin reactions Stevens-Johnson syndrome Bullous dermatitis Erythema multiforme Toxic epidermal necrolysis Increased creatine kinase blood levels Rhabdomyolysis Black Box Warnings In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (aged <24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses This increase was not seen in patients aged ≥24 years A slight decrease in suicidal thinking was seen in adults aged ≥65 years compared with placebo In children and young adults, 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 patientsContraindications Hypersensitivity Within 14 days of administration of MAOIs (serotonin syndrome) Patients receiving linezolid or methylene blue IV Cautions Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs Screen for bipolar disorder; MDD episode may be the initial presentation of bipolar disorder; generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase precipitation of mixed/manic episode in patients at risk for bipolar disorder Rare reports of activation of mania/hypomania Agranulocytosis reported; if sign/symptoms develop (eg, sore throat, fever, stomatitis, infection with low WBC count), discontinue mirtazapine and closely monitor Potentially life-threatening serotonin syndrome reported with SNRIs and SSRIs alone, but also if coadministered with other serotonergic drugs Pupillary dilation that occurs with antidepressant drugs may trigger an angle-closure attack in patients with anatomically narrow angles who have not had iridectomy Upon discontinuation (particularly when abrupt), the following symptoms may occur: dizziness, abnormal dreams, sensory disturbances (including paresthesia and electric shock sensations), agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting, and sweating Akathisia, characterized by subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still; most likely to occur within first few weeks; increasing dose may be detrimental Hyponatremia (rare) reported Somnolence reported in ~50% of patients Dizziness, increased appetite/weight gain, and transaminase elevations reported Postmarketing reports of QT prolongation, torsades de pointes, ventricular tachycardia, and sudden death; majority reported in association with overdose or in patients with other risk factors for QT prolongation, including concomitant use of QTc-prolonging medicines Drug interaction overview Caution if coadministered with other drugs that prolong QT interval Monitor INR if higher doses of mirtazapine are coadministered with warfarin Avoid use with alcohol and other CNS depressants; may cause additive somnolence and dizziness Risk of serotonin syndrome Contraindicated with MAOIs; do not start mirtazapine if being treated with IV methylene blue or linezolid Caution with other serotonergic drugs CYP inducers Strong CYP inducers (eg, phenytoin, carbamazepine, rifampin) may increase mirtazapine clearance by ~2-fold If coadministered with strong CYP inducers, mirtazapine dose may need to be increased; conversely, if strong CYP inducer is stopped, decrease mirtazapine dose Strong CYP3A4 inhibitors Strong CYP3A4 inhibitor increase mirtazapine peak plasma levels and AUC Caution if coadministered; mirtazapine dose may need to be lowered Pregnancy Apregnancy exposure registry monitors pregnancy outcomes in women exposed to antidepressants during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/. Prolonged experience with therapy in pregnant women, based on published observational studies and postmarketing reports, has not reliably identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants; this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at beginning of pregnancy Consider risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum; it should be used during pregnancy only if clearly needed Animal studies Reproduction studies in pregnant rats and rabbits at doses up to 100 mg/kg and 40 mg/kg, respectively (20 and 17 times the maximum recommended human dose [MRHD] on an mg/m2 basis, respectively), have revealed no evidence of teratogenic effects However, in rats, there was an increase in postimplantation losses in dams treated with mirtazapine Lactation Data from published literature report presence of drug in human milk at low levels with relative infant doses ranging between 0.6 and 2.8% of the maternal weight-adjusted dose; no adverse effects on breastfed infant reported in most cases of maternal use of drug; there are no data on effects of drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal conditionPregnancy 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 Tetracyclic structure different from SSRIs, TCAs and MAOIs; through its central presynaptic alpha2-adrenergic antagonist effects, stimulates norepinephrine and serotonin release; potent antagonist of 5-HT2 and 5-HT3 serotonin and histamine receptors; is a moderate alpha1 adrenergic and muscarinic antagonist Absorption Bioavailability: 50% Peak serum time: 2 hr Distribution Protein bound: 85% Vd: 4.5 L/kg Metabolism Hepatic CYP450 enzymes CYP1A2, CYP2D6, CYP3A4 Metabolites: Inactive Elimination Half-life: 20-40 hr Excretion: Urine (75%); feces (15%) Oral Administration May take with or without food Storage Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) Protect from light and moisture BRAND FORM. UNIT PRICE PILL IMAGE mirtazapine oral- 30 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 45 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 45 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 45 mg tabletmirtazapine oral- 7.5 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 45 mg tabletmirtazapine oral- 45 mg tabletmirtazapine oral- 15 mg tabletmirtazapine oral- 30 mg tabletmirtazapine oral- 7.5 mg tabletmirtazapine oral- 45