Use Caution/Monitor. thioridazine and trifluoperazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and trifluoperazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)thioridazine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.trihexyphenidylMonitor Closely (2)trihexyphenidyl decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor. thioridazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.trimethoprimMonitor Closely (1)thioridazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.trimipramineMonitor Closely (1)thioridazine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)trimipramine, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. trimipramine, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.triprolidineMonitor Closely (1)triprolidine and thioridazine both increase sedation. Use Caution/Monitor.triptorelinSerious - Use Alternative (1)triptorelin increases toxicity of thioridazine by QTc interval. Avoid or Use Alternate Drug. Increases risk of torsades de pointes.trofinetideMonitor Closely (1)trofinetide will increase the level or effect of thioridazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).tropisetronMonitor Closely (1)thioridazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)thioridazine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.trospium chlorideMonitor Closely (3)trospium chloride decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. trospium chloride decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor. thioridazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.umeclidinium bromide/vilanterol inhaledSerious - Use Alternative (1)thioridazine 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.ustekinumabMonitor Closely (1)ustekinumab, thioridazine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.vandetanibSerious - Use Alternative (1)thioridazine, 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.vecuroniumMonitor Closely (3)vecuronium decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. vecuronium decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor. thioridazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.vemurafenibSerious - Use Alternative (1)vemurafenib increases levels of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP2D6 substrate drug. Combination may increase risk QT prolongation.venlafaxineSerious - Use Alternative (2)thioridazine and venlafaxine both increase QTc interval. Avoid or Use Alternate Drug. venlafaxine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)thioridazine 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.voclosporinMonitor Closely (1)voclosporin, thioridazine. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)thioridazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.vorinostatContraindicated (1)vorinostat and thioridazine both increase QTc interval. Contraindicated.xylometazolineMonitor Closely (2)thioridazine, 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. thioridazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbeSerious - Use Alternative (1)yohimbe decreases effects of thioridazine by pharmacodynamic antagonism. Contraindicated.yohimbineMonitor Closely (2)thioridazine, 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. thioridazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)thioridazine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (2)thioridazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. thioridazine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolpidemMonitor Closely (1)thioridazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performancezotepineMonitor Closely (2)thioridazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. thioridazine and zotepine both increase sedation. Use Caution/Monitor. Frequency Not Defined EPS (muscle stiffness, dystonia, parkinsonism, tardive dyskinesia, akathisia) (60%) NMS (infrequent but serious) Sedation Anticholinergic effects Weight gain Oligomenorrhea/amenorrhea Erectile dysfunction Insomnia Restlessness Anxiety Euphoria Agitation Depression Weakness Headache Cerebral edema Poikilothermia Orthostatic hypotension Tachycardia Dizziness Lens opacities (prolonged use) Anorexia Dyspepsia Constipation Ileus Blood dyscrasia ECG changes Photosensitivity Pruritis Diarrhea Galactorrhea Ejaculatory disorder Seizure (rare) Priapism (rare) Cholestatic jaundice (rare) Black Box Warnings Patients with dementia-related psychosis who 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 (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature; this drug is not approved for the treatment of patients with dementia-related psychosis Shown to prolong QTc interval in a dose-related manner; drugs with this potential have been associated with Torsades de pointes type arrhythmias and sudden death; due to potential for significant, possibly life-threatening, proarrhythmic effects, therapy should be reserved for use in treatment of schizophrenic patients who fail to show acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or inability to achieve effective dose due to intolerable adverse effects from those drugsContraindications Documented hypersensitivity to phenothiazines Coadministration with cytochrome P450 2D6 isozyme inhibitors (eg, fluoxetine and paroxetine) and certain other drugs (eg, fluvoxamine, propranolol, and pindolol) Patients who are known to have a genetic defect leading to reduced levels of activity of P450 2D6 Patients with hypertensive or hypotensive heart disease of extreme degree Patients in comatose state Severe CNS depression Severe hyper-/hypotensive heart disease Cautions Avoid using in children with suspected Reye's syndrome Hypotension may be particularly severe in patients with pheochromocytoma or mitral insufficiency Depresses hypothalamic thermoregulatory mechanism; exposure to extreme temperatures may cause hypo- or hyperthermia Leukopenia and/or agranulocytosis and convulsive seizures reported but infrequent; in schizophrenic patients with epilepsy, anticonvulsant medication should be maintained during treatment Pigmentary retinopathy, which has been observed primarily in patients taking larger than recommended doses, is characterized by diminution of visual acuity, brownish coloring of vision, and impairment of night vision; examination of the fundus discloses deposits of pigment; the possibility of this complication may be reduced by remaining within recommended limits of dosage Where patients are participating in activities requiring complete mental alertness (eg, driving) it is advisable to administer the phenothiazines cautiously and to increase the dosage gradually Female patients appear to have a greater tendency to orthostatic hypotension than male patients; administration of epinephrine should be avoided in treatment of drug-induced hypotension as it may induce a reversed epinephrine effect on occasion; should a vasoconstrictor be required, the most suitable are levarterenol and phenylephrine An increase in mammary neoplasms has been found in rodents after chronic administration of neuroleptic drugs; neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time Prolactin Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration; tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients Proarrhythmic effects Certain factors may increase risk of Torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia, hypokalemia, concomitant use of other drugs that prolong the QTc interval, presence of congenital prolongation of the QT interval, and for thioridazine in particular, its use in patients with reduced activity of P450 2D6 or its coadministration with drugs that may inhibit P450 2D6 or by some other mechanism interfere with the clearance of thioridazine Patients being considered for thioridazine treatment should have baseline ECG performed and serum potassium levels measured; serum potassium should be normalized before initiating treatment and patients with a QTc interval > 450 msec should not receive the therapy; may also be useful to periodically monitor ECG’s and serum potassium during thioridazine treatment, especially during a period of dose adjustment; therapy should be discontinued in patients who are found to have a QTc interval over 500 msec Patients receiving therapy who experience symptoms that may be associated with occurrence of Torsades de pointes (eg, dizziness, palpitations, or syncope) may warrant further cardiac evaluation; in particular, Holter monitoring should be considered Tardive dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs; it is impossible to rely upon prevalence estimates to predict, at inception of antipsychotic treatment, which patients are likely to develop the syndrome; whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown The risk of developing the syndrome and likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase; syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn; antipsychotic treatment itself, however, may suppress (or partially suppress) signs and symptoms of syndrome and thereby may possibly mask underlying disease process; effect that symptomatic suppression has upon long-term course of syndrome is unknown Given these considerations, antipsychotics should be prescribed in a manner that is most likely to minimize occurrence of tardive dyskinesia; chronic antipsychotic treatment should generally be reserved for patients who suffer from chronic illness that, is known to respond to antipsychotic drugs and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate In patients who do require chronic treatment, the smallest dose and shortest duration of treatment producing a satisfactory clinical response should be sought; the need for continued treatment should be reassessed periodically If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome It has been suggested that people who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) to one may be more prone to demonstrate a reaction to others; physicians should carefully consider benefit versus risk when treating less severe disorders Neuroleptic malignant syndrome A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported in association with antipsychotic drugs; clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias) The diagnostic evaluation of patients with this syndrome is complicated; in arriving at a diagnosis, it is important to identify cases where clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS); other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system (CNS)