Caution/Monitor.vandetanibSerious - Use Alternative (1)paliperidone, 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 paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. vecuronium decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor. paliperidone increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.vemurafenibSerious - Use Alternative (1)vemurafenib and paliperidone both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.venetoclaxSerious - Use Alternative (1)paliperidone will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.venlafaxineMonitor Closely (2)venlafaxine, paliperidone. 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). paliperidone and venlafaxine both increase QTc interval. Use Caution/Monitor.verapamilMonitor Closely (1)verapamil will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)paliperidone 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 (1)vilazodone, paliperidone. 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).voclosporinMonitor Closely (1)voclosporin, paliperidone. Either increases effects of the other by QTc interval. Use Caution/Monitor.voriconazoleMonitor Closely (1)paliperidone and voriconazole both increase QTc interval. Use Caution/Monitor.vorinostatSerious - Use Alternative (1)vorinostat and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.xylometazolineMonitor Closely (1)paliperidone increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)paliperidone increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)paliperidone and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (3)paliperidone and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely. paliperidone and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. paliperidone and ziprasidone both increase sedation. Use Caution/Monitor.zolmitriptanMonitor Closely (1)zolmitriptan, paliperidone. 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).zotepineMonitor Closely (2)paliperidone and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. paliperidone and zotepine both increase sedation. Use Caution/Monitor. >10% Invega Hafyera Upper respiratory tract infection (12%) Injection site reactions (11%) Invega Sustenna Injection site reaction (12%) Oral (adults) Extrapyramidal symptoms (7-20%) Akathisia (4-17%) Tachycardia (12-14%) Headache (11-14%) Somnolence (6-11%) Oral (children and adolescents) Somnolence (9-26%) Extrapyramidal symptoms (4-23%) Akathisia (4-17%) Vomiting (6-11%) 1-10% Invega Hafyera Weight increased (9%) Headache (7%) Extrapyramidal symptoms (7%) Parkinsonism (5%) Akathisia (4%) Hyperkinesia (4%) Urinary tract infection (3%) Back pain (3%) Musculoskeletal pain (3%) Psychosis (3%) Anxiety (3%) Insomnia (3%) Diarrhea (2%) Dyskinesia (2%) Dystonia (1%) Invega Sustenna Weight increased (10%) Headache (7%) Parkinsonism (4-6%) Hyperkinesia (5%) Upper respiratory tract infection (5%) Akathisia (3-5%) Tremor (2%) Dystonia (1%) Invega Trinza Upper respiratory tract infection (10%) Headache (9%) Weight increased (9%) Parkinsonism (4-6%) Hyperkinesia (5%) Akathisia (3-5%) Injection site reaction (3%) Urinary tract infection (3%) Dyskinesia (1-3%) Tremor (1%) Dystonia (1%) Oral (adults) Salivary hypersecretion (<4%) Upper abdominal pain (1-3%) Dry mouth (1-3%) Bundle branch block (<3%) Sinus arrhythmia (<3%) Atrioventricular (AV) block (1-2%) Fatigue (1-2%) Asthenia (<2%) Oral (children and adolescents) Tachycardia (6-9%) Anxiety (4-9%) Increased weight (2-7%) Salivary hypersecretion (2-6%) Dizziness (2-6%) Amenorrhea (6%) Galactorrhea (4%) Nasopharyngitis (4%) Gynecomastia (3%) Blurred vision (3%) Dry mouth (3%) Swollen tongue (3%) Lethargy (3%) Tongue paralysis (3%) Asthenia (2-3%) Fatigue (2-3%) Epistaxis (2%) <1% Invega Hafyera Tremor Invega Sustenna Dyskinesia Urinary tract infection Frequency Not Defined Invega Hafyera Blood and lymphatic system disorders: Anemia Cardiac disorders: Bradycardia, tachycardia Ear and labyrinth disorders: Vertigo Gastrointestinal disorders: Constipation, nausea, vomiting General disorders and administration site conditions: Fatigue Hepatobiliary disorders: Transaminases increased Infections and infestations: Cystitis, respiratory tract infection, tonsillitis Metabolism and nutritional disorders: Decreased appetite, increased appetite, weight decreased Psychiatric disorders: Depression Reproductive system and breast disorders: Breast pain, menstrual disorder Skin and SC tissue disorders: Rash Vascular disorders: Hypertension Invega Sustenna and Trinza Cardiac disorders: AV block first degree, bundle branch block, palpitations, postural orthostatic tachycardia syndrome Eye disorders: Eye movement disorder, eye rolling, oculogyric crisis, vision blurred Gastrointestinal disorders: Abdominal discomfort/abdominal pain upper, diarrhea, dry mouth, toothache General disorders and administration site conditions: Asthenia, chest discomfort Immune system disorders: Hypersensitivity Investigations: Electrocardiogram (ECG) abnormal Metabolism and nutrition disorders: Hyperinsulinemia Musculoskeletal and connective tissue disorders: Myalgia, pain in extremity, joint stiffness, muscle spasms, muscle twitching, nuchal rigidity Nervous system disorders: Bradykinesia, cerebrovascular accident, convulsion, dizziness, dizziness postural, dysarthria, hypertonia, lethargy, oromandibular dystonia, psychomotor hyperactivity, syncope Psychiatric disorders: Agitation, nightmare Reproductive system and breast disorders: Breast discharge, erectile dysfunction, gynecomastia, sexual dysfunction Respiratory, thoracic, and mediastinal disorders: Cough Skin and SC tissue disorders: Drug eruption, eczema, pruritus, pruritus generalized, urticaria Vascular disorders: Hypotension, orthostatic hypotension Tablets Cardiac disorders: Bradycardia, palpitations Eye disorders: Eye movement disorder Gastrointestinal disorders: Flatulence General disorders: Edema Immune system disorders: Anaphylactic reaction Infections and infestations: Urinary tract infection Investigations: ALT/AST increased Musculoskeletal and connective tissue disorders: Arthralgia, pain in extremity Nervous system disorders: Opisthotonos Psychiatric disorders: Agitation, insomnia, nightmare Reproductive system and breast disorders: Breast discomfort, menstruation irregular, retrograde ejaculation Respiratory, thoracic, and mediastinal disorders: Nasal congestion Skin and SC tissue disorders: pruritus, rash Vascular disorders: Hypertension Postmarketing Reports Angioedema, catatonia, ileus, somnambulism, swollen tongue, thrombotic thrombocytopenic purpura, urinary incontinence, and urinary retention Invega Sustenna Anaphylactic reactions Black Box Warnings Increased mortality in elderly patients with dementia-related psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death Not approved for use in patients with dementia-related psychosis Contraindications Documented hypersensitivity to paliperidone or risperidone Cautions Increased incidence of cerebrovascular adverse reactions (eg, stroke, transient ischemic attack, including fatalities) reported Neuroleptic malignant syndrome (NMS) reported in association with antipsychotic drugs; if NMS is suspected, discontinue treatment and provide symptomatic treatment and monitoring May induce orthostatic hypotension; use with caution in patients with known cardiovascular or cerebrovascular disease and patients predisposed to hypotension Motor instability, somnolence, and orthostatic hypotension reported, which may lead to falls and, consequently, fractures or other fall-related injuries; assess risk of falls when initiating treatment and recurrently for patients receiving repeated doses, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects Hyperprolactinemia reported; may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion and gonadal steroidogenesis in female and male patients; galactorrhea, amenorrhea, gynecomastia, and impotence reported; long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects May cause CNS depression (somnolence, sedation, dizziness), which may impair abilities to perform tasks requiring mental alertness, including operating heavy machinery Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of aspiration pneumonia Rare cases of priapism reported Use caution when prescribing to patients who will be experiencing conditions which may contribute to elevation in core body temperature (eg, exercising strenuously, extreme heat exposure, concomitant medication with anticholinergic activity, dehydration) Avoid use in severe preexisting GI stenosis Rare cases of intraoperative floppy iris syndrome reported with risperidone in patients undergoing cataract surgery; paliperidone is active metabolite of risperidone; use caution; benefits or risks of interrupting paliperidone or risperidone use prior to cataract surgery not established Patients with Parkinson disease may be more sensitive to CNS and extrapyramidal effects May mask toxicity of other drugs or conditions (eg, intestinal obstruction) due to antiemetic effects May increase risk of death in elderly patients with dementia-related psychosis Use caution in patients with history of suicidal ideation or any form of psychotic illness; may increase risk of suicide attempt Certain circumstances may increase risk of the occurrence of Torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval, including bradycardia; hypokalemia or hypomagnesemia; concomitant use of other drugs that prolong the QTc interval; and presence of congenital prolongation of the QT interval Patient should see healthcare provider or go to the nearest emergency room right away if erection lasts more than 4 hr Tardive dyskinesia Tardive dyskinesia may develop Risk of developing tardive dyskinesia and likelihood that it will become irreversible appears to increase with duration of treatment and cumulative dose; syndrome may develop after relatively brief treatment periods or after discontinuing treatment May remit, partially or completely, if treatment withdrawn; antipsychotic treatment may suppress (or partially suppress) signs and symptoms of syndrome and thereby possibly mask underlying process Reserve chronic antipsychotic treatment for patients who suffer from a chronic illness known to respond to antipsychotic drugs, and for whom alternative are not available or appropriate In patients who require chronic treatment, use lowest dose and the shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued treatment Metabolic changes Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk (eg, hyperglycemia, dyslipidemia, hyperprolactinemia, body weight gain) Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have also been reported Regularly monitor patients diagnosed with DM who started an atypical antipsychotic for worsening of glucose control Patients with risk factors for DM (eg, obesity, family history of diabetes) who are starting treatment should undergo fasting blood glucose testing upon initiation and periodically during treatment Monitor any patient treated with atypical antipsychotics for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness Leukopenia, neutropenia, and agranulocytosis Leukopenia/neutropenia and agranulocytosis reported Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur If history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood cell count (CBC) frequently during first few months of therapy; discontinue if WBC decline <1000/ mm3 and continue monitoring WBC until recovery Drug interaction overview Substrate of P-gp and CYP3A4 Centrally-acting drugs and alcohol Use with caution Centrally-acting drugs and alcohol may modulate the CNS effects of paliperidone Drugs that cause orthostatic hypotension Monitor orthostatic vital signs in patients who are vulnerable to hypertension Drugs that induce orthostatic hypotension may enhance the orthostatic hypotensive effects of paliperidone Strong CYP3A4 and P-gp inducers (Invega Hafyera only) Avoid coadministration of CYP3A4 and/or P-gp inducers If a strong inducer is necessary, consider using paliperidone extended-release tablets Levodopa and other dopamine agonists Monitor and manage appropriately Paliperidone may antagonize the effect of levodopa and other dopamine agonists Drugs that prolong QT interval Avoid coadministration with other drugs that are known to prolong QTc including Class 1A (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (eg, chlorpromazine, thioridazine), fluoroquinolones (eg, moxifloxacin), or any other class of medications known to prolong the QTc interval Paliperidone may enhance the QT-prolonging effects of such drugs Pregnancy Neonates exposed to antipsychotic drugs during third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery Available data of pregnant females exposed to paliperidone have not