tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.trospium chlorideMonitor Closely (3)trospium chloride decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. trospium chloride decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor. trifluoperazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.valbenazineMonitor Closely (1)valbenazine and trifluoperazine both decrease QTc interval. Use Caution/Monitor.vecuroniumMonitor Closely (3)vecuronium decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. vecuronium decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor. trifluoperazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.venlafaxineMonitor Closely (3)venlafaxine, trifluoperazine. 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). trifluoperazine and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely. venlafaxine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.vilazodoneMonitor Closely (1)vilazodone, trifluoperazine. 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).voriconazoleMonitor Closely (1)trifluoperazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.vorinostatMonitor Closely (1)vorinostat and trifluoperazine both decrease QTc interval. Use Caution/Monitor.xylometazolineMonitor Closely (2)trifluoperazine, 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. trifluoperazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbeSerious - Use Alternative (1)yohimbe decreases effects of trifluoperazine by pharmacodynamic antagonism. Contraindicated.yohimbineMonitor Closely (2)trifluoperazine, 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. trifluoperazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)trifluoperazine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (2)trifluoperazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. trifluoperazine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trifluoperazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zolmitriptanMonitor Closely (1)zolmitriptan, trifluoperazine. 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)trifluoperazine 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)trifluoperazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. trifluoperazine and zotepine both increase sedation. Use Caution/Monitor. Frequency Not Defined EPS (60%; muscle stiffness, dystonia, parkinsonism, tardive dyskinesia, akathisia) 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 d/o 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.Contraindications Hypersensitivity to phenothiazines or excipients Comatose or greatly depressed states due to central nervous system depressants, existing blood dyscrasias, bone marrow depression, and preexisting liver damage Cautions Thrombocytopenia and anemia reported in patients receiving therapy; agranulocytosis and pancytopenia also reported; warn patients to report sudden appearance of sore throat or other signs of infection; if white blood cell and differential counts indicate cellular depression, stop treatment and start antibiotic and other suitable therapy Jaundice of cholestatic type of hepatitis or liver damage reported; if fever with grippe-like symptoms occurs, appropriate liver studies should be conducted; if tests indicate an abnormality, stop treatment One result of therapy may be an increase in mental and physical activity; for example, a few patients with angina pectoris have complained of increased pain while taking the drug; patients with angina should be observed carefully and, if an unfavorable response noted, the drug should be withdrawn Because hypotension has occurred, large doses and parenteral administration should be avoided in patients with impaired cardiovascular systems; to minimize occurrence of hypotension after injection, keep patient lying down and observe for at least 1/2 hour; if hypotension occurs from parenteral or oral dosing, place patient in head-low position with legs raised If a vasoconstrictor is required, norepinephrine bitartrate and phenylephrine hydrochloride are suitable; other pressor agents, including epinephrine, should not be used as they may cause a paradoxical further lowering of blood pressure Since certain phenothiazines reported to produce retinopathy, the drug should be discontinued if ophthalmoscopic examination or visual field studies should demonstrate retinal changes; an antiemetic action of this drug may mask signs and symptoms of toxicity or overdosage of other drugs and may obscure diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor, and Reye’s syndrome With prolonged administration at high dosages, the possibility of cumulative effects, with sudden onset of severe central nervous system or vasomotor symptoms, should be kept in mind Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration; tissue culture experiments indicate that approximately 1/3 of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescribing of these drugs is contemplated in a patient with a previously detected breast cancer Although disturbances such as galactorrhea, amenorrhea, gynecomastia and impotence reported, the clinical significance of elevated serum prolactin levels is unknown for most patients; an increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs Neither clinical 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 Chromosomal aberrations in spermatocytes and abnormal sperm demonstrated in rodents treated with certain antipsychotics Because phenothiazines may interfere with thermoregulatory mechanisms, use caution in persons who will be exposed to extreme heat As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, trifluoperazine should be used with caution in patients with glaucoma; phenothiazines may diminish effect of oral anticoagulants Phenothiazines can produce alpha-adrenergic blockade; concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concurrently; thiazide diuretics may accentuate orthostatic hypotension that may occur with phenothiazines Phenothiazines may lower convulsive threshold; dosage adjustments of anticonvulsants may be necessary; potentiation of anticonvulsant effects does not occur; however, it has been reported that phenothiazines may interfere with metabolism of phenytoin and thus precipitate phenytoin toxicity; drugs which lower seizure threshold, including phenothiazine derivatives, should not be used with metrizamide As with other phenothiazine derivatives, trifluoperazine hydrochloride should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours post-procedure, and should not be used for control of nausea and vomiting occurring either prior to myelography or post-procedure with metrizamide To lessen likelihood of adverse reactions related to cumulative drug effects, patients with a history of long-term therapy with trifluoperazine hydrochloride and/or other antipsychotics should be evaluated periodically to decide whether maintenance dosage could be lowered, or drug therapy discontinued The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results Leukopenia, neutropenia, and agranulocytosis In clinical trial and post-marketing experience, events of leukopenia/neutropenia and agranulocytosis reported temporally related to antipsychotic agents Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia; patients with a preexisting low WBC or a history of drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during first few months of therapy and should discontinue therapy at first sign of a decline in WBC in the absence of other causative factors Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms occur Patients with severe neutropenia (absolute neutrophil count < 1000/mm ) should discontinue therapy and have their WBC followed until recovery Tardive dyskinesia Given the likelihood that some patients exposed chronically to antipsychotics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk; the decision to inform patients and/or their guardians must obviously take into account clinical circumstances and competency of patient to understand information provided Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs; although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, 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; both risk of developing the syndrome and likelihood that it will become irreversible are believed to increase as duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase However, the 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 the syndrome and thereby may possibly mask the underlying disease process; the effect that symptomatic suppression has on long-term course of the 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 a 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, consider drug discontinuation; however, some patients may require treatment despite presence of syndrome Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) 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 differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology; the management of NMS should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems for which specific treatments are available There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS; if a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered The patient should be carefully monitored; recurrences of NMS reported; an encephalopathic syndrome