interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.venetoclaxSerious - Use Alternative (1)iloperidone will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a moderate CYP3A inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.venlafaxineMonitor Closely (4)venlafaxine, iloperidone. 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). iloperidone increases levels of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4. venlafaxine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. iloperidone and venlafaxine both increase QTc interval. Use Caution/Monitor.verapamilMonitor Closely (2)verapamil will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. iloperidone increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)iloperidone 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 (2)vilazodone, iloperidone. 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). iloperidone increases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.vinblastineMonitor Closely (1)iloperidone increases levels of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.vincristineMonitor Closely (1)iloperidone increases levels of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.vincristine liposomalMonitor Closely (1)iloperidone increases levels of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.vinorelbineMonitor Closely (1)iloperidone increases levels of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.voclosporinMonitor Closely (2)voclosporin, iloperidone. Either increases effects of the other by QTc interval. Use Caution/Monitor. iloperidone will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.voriconazoleMonitor Closely (2)voriconazole will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. iloperidone and voriconazole both increase QTc interval. Use Caution/Monitor.vorinostatSerious - Use Alternative (1)vorinostat and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.xylometazolineMonitor Closely (1)iloperidone increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)iloperidone increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.zanubrutinibMonitor Closely (1)iloperidone will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. ziconotideMonitor Closely (1)iloperidone and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (3)iloperidone and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely. iloperidone and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. iloperidone and ziprasidone both increase sedation. Use Caution/Monitor.zolmitriptanMonitor Closely (1)zolmitriptan, iloperidone. 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)iloperidone increases levels of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.zonisamideMonitor Closely (1)iloperidone increases levels of zonisamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.zotepineMonitor Closely (3)iloperidone increases effects of zotepine by pharmacodynamic synergism. Use Caution/Monitor. iloperidone and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. iloperidone and zotepine both increase sedation. Use Caution/Monitor. >10% Dizziness (20%) Dry mouth (15%) Nausea (10%) Somnolence (10%) Tachycardia (12%) 1-10% (selected) Diarrhea Ejaculation failure Myalgia Nasal congestion Orthostatic hypotension Palpitations Urinary incontinence Weight gain <1% (selected) Amenorrhea Edema Hypothyroidism Frequency Not Defined (selected) Priapism Postmarketing Reports Retrograde ejaculation Hypersensitivity reactions (including anaphylaxis; angioedema; throat tightness; oropharyngeal swelling; swelling of the face, lips, mouth, and tongue; urticaria; rash; and pruritus) 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 psychosisContraindications Hypersensitivity; anaphylaxis, angioedema, and other hypersensitivity reactions reported Cautions Prolongs QT interval; caution with other drugs/conditions that increase QTc Not recommended in hepatic impairment May cause anticholinergic side effects (eg., confusion, agitation) Three cases of priapism reported in pre-marketing program; drugs with alpha-adrenergic blocking effects reported to induce priapism; this drug shares this pharmacologic activity; severe priapism may require surgical intervention Should be avoided in patients with a known genetic susceptibility to congenital long QT syndrome and with a history of cardiac arrhythmias May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; for patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy Can induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; use with caution in patients with known cardiovascular disease (eg, heart failure, history of myocardial infarction, ischemia, or conduction abnormalities), cerebrovascular disease, or conditions that predispose patient to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications); monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension Use caution in patients with history of seizures or with conditions that lower seizure threshold Possibility of suicide attempt is inherent in psychotic illness, and close supervision of high-risk patients should accompany drug therapy; prescriptions should be written for smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose Disruption of body’s ability to reduce core body temperature has been attributed to antipsychotic agents; appropriate care is advised when prescribing for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, eg, exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration Esophageal dysmotility and aspiration associated with antipsychotic drug use; aspiration pneumonia is a common cause of morbidity and mortality in elderly patients; this medication and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia Leukopenia, neutropenia, and agranulocytosis In clinical trial and postmarketing experience, events of leukopenia/neutropenia reported temporally related to antipsychotic agents; agranulocytosis (including fatal cases) also reported Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia; patients with a pre-existing 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 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 or signs occur; patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue therapy and have their WBC followed until recovery Hyperprolactinemia As with other drugs that antagonize dopamine D2 receptors, this drug elevates prolactin levels; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion; this, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients Galactorrhea, amenorrhea, gynecomastia, and impotence reported with prolactin-elevating compounds; long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients 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 previously detected breast cancer Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans; the available evidence is considered too limited to be conclusive at this time Metabolic changes Atypical antipsychotics have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain; while all atypical antipsychotic drugs have been shown to produce some metabolic changes, each drug in the class has its own specific risk profile Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death Undesirable alterations in lipids reported in patients treated with atypical antipsychotics Monitor blood glucose of high risk patients Hyperglycemia and diabetes mellitus Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, reported; assessment of relationship between atypical antipsychotic use and glucose abnormalities is complicated by possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and increasing incidence of diabetes mellitus in general population Relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood; however, epidemiological studies suggest an increased risk of hyperglycemia-related adverse events in patients treated with atypical antipsychotics Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control; patients with risk factors for diabetes mellitus (eg, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at beginning of treatment and periodically during treatment Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness; patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing; in some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug Tardive dyskinesia Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, which 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 on 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 tardive dyskinesia and likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic administered increases; however,