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Volume 6

Therapeutic Considerations

Exploring the Use of UZEDY Early in Schizophrenia Treatment

MAY 2026 | 7 MIN READ

UZEDY Therapeutic Considerations hero

Early and Often: Introducing LAIs to the Schizophrenia Treatment Discussion

The clinical course of schizophrenia is often characterized by recurrent relapse.1,2 Many of the consequences of relapse, which range from treatment resistance to arrests and homelessness, may begin after the first relapse.3-5 For this reason, early intervention and taking steps to delay relapse is important for patients with schizophrenia.6 Long-acting injectables (LAIs) provide extended dosing intervals with fewer opportunities to miss a dose, and the expectation of sustained, stable therapeutic levels of antipsychotic after receiving an injection.7,8 The American Psychiatric Association guidelines and experts recommend LAIs for any patient for whom long-term antipsychotic therapy is indicated, and should be introduced early and often, as part of a comprehensive discussion of treatment options.7-12 Despite this, LAIs are often reserved as a last resort for patients or not offered by clinicians due to the perception that the patient will not accept an LAI or past rejection of LAIs.13,14 In reality, studies suggest that patients may consider LAIs, after learning about their advantages and disadvantages, and some patients may prefer this option.15-17 Patients may not accept an LAI the first time, so it is important to introduce LAIs early to the treatment conversation and revisit them on a regular basis as appropriate. Consistent dialogue and communication strategies such as motivational interviewing may encourage patients to reconsider the potential benefits of an LAI even if they have rejected the option before.18,19 There are a number of LAIs currently available for schizophrenia treatment, each with different pharmacokinetic, administration, and usage attributes that may impact clinical decision making.20-24 UZEDY® is a different kind of LAI for adults with schizophrenia that utilizes the innovative drug delivery platform SteadyTeqTM to offer a range of features that clinicians and patients may want to consider when selecting an LAI.25,26

Efficacy and Safety Data of UZEDY From Clinical Trials

UZEDY was evaluated in the double-blind, placebo-controlled, randomized relapse prevention study RISE, which compared UZEDY once monthly (Q1M) and once every 2 months (Q2M) with placebo in patients with schizophrenia.25-27 In RISE, patients receiving UZEDY Q1M demonstrated a significantly reduced risk of relapse by 80% compared with patients receiving placebo (Figure 1).25 In patients receiving UZEDY Q2M, the reduction in risk of relapse was 62.5% compared with placebo.25

80%
Reduction in risk of relapse with UZEDY Q1M vs placebo25
62.5%
Reduction in risk of relapse with UZEDY Q2M vs placebo25

Figure 1. Patients With Impending Relapse

Figure 1. Patients With Impending Relapse

Q1M, once per month.

Exploratory and post hoc analyses of these studies were conducted at 6 months and 1 year. At week 24, the relapse-free rate for patients receiving UZEDY Q1M was 93%, while it was 89% for those receiving UZEDY Q2M, compared with 72% in the placebo group.27 At the one-year mark, the relapse-free rates for the UZEDY Q1M and Q2M groups were 92% and 87%, respectively, compared with 63% for the placebo group (Figure 2).27 It is important to remember that, due to the exploratory and post hoc nature of these analyses, no determination of statistical significance can be made, and conclusions should not be drawn from these findings.

93%
Relapse-free rate for patients receiving UZEDY Q1M at week 2427
92%
Relapse-free rate for patients receiving UZEDY Q1M at 1 year27

Figure 2. Relapse-Free Rate of Patients at 6 Months and 1 Year

Figure 2. Relapse-Free Rate of Patients at 6 Months and 1 Year

The safety profile of UZEDY for patients with schizophrenia is based on adequate and well-controlled studies of oral risperidone, which has been well characterized, and is expected to be similar to that of corresponding oral risperidone doses of 2 to 5 mg daily.26 The most common adverse reactions with oral risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.26

Features to Consider When Identifying Candidates for UZEDY

In addition to efficacy and safety, there are several important factors for clinicians and patients to consider when selecting an LAI. Key considerations may include patient preferences for features such as dosing interval or needle size and clinician discretion regarding administration and pharmacokinetic features. Table 1 includes a list of features of some LAIs available for schizophrenia treatment.20-24,26 Although this information should not be construed to imply any difference in safety, efficacy, or clinical outcomes, these features may be considered as part of a larger discussion about treatment options.


Table 1. Pharmacokinetic, Administration, and Usage Attributes of LAIs

Table 1. Pharmacokinetic, Administration, and Usage Attributes of LAIs

*No reconstitution or premixing required.


Figure 4. Needle Sizes of Available LAIs

Figure 4. Needle Sizes of Available LAIs

Only UZEDY offers a pharmacokinetic profile that attains therapeutic plasma concentrations within 6 to 24 hours of administration. The net result is that UZEDY maintained clinically relevant plasma levels throughout the dosing interval, and steady-state levels of risperidone and its metabolite, 9-hydroxyrisperidone, were approached within 2 months of initiation of UZEDY.26 The dosing interval and dosage strength of UZEDY can be tailored to the individual needs of patients with schizophrenia.26 UZEDY may be a suitable option for patients who don't want to take a daily pill or prefer less frequent dosing, as it is available in 1- or 2-month dosing for schizophrenia.26 UZEDY also does not require oral supplementation or loading doses when initiating treatment.26 This feature streamlines the treatment initiation process and offers a single-injection reinitiation protocol for patients who miss their regularly scheduled dose.26 In a companion survey involving 63 patients, 24 physicians, and 25 nurses assessing perceptions regarding the ease of use and satisfaction with UZEDY, 90% of patients with schizophrenia surveyed indicated a preference for continuing UZEDY over their prior schizophrenia medications.28

In summary, UZEDY can help prevent relapse and has a safety profile akin to the established profile of oral risperidone, which is familiar to many healthcare providers. The initiation process with UZEDY is streamlined, with no loading dose or oral supplementation required. It has demonstrated relapse prevention, and it has a safety profile consistent with the known safety profile of oral risperidone.2,5 Patients and caregivers alike have observed that the streamlined dosing and administration process of UZEDY make it easy to receive and deliver.6 In addition to the perceived ease of administration, insights from real-world data suggest persistence among patients treated with UZEDY through the period analyzed.9

Key Takeaways: Exploring the Use of UZEDY Early in Schizophrenia Treatment
  • Relapse in schizophrenia can have devastating consequences; LAIs should be introduced early and often as part of a comprehensive treatment discussion, consistent with APA guidelines3-12
  • UZEDY significantly reduced the risk of relapse vs placebo in the RISE study: by 80% with Q1M dosing and by 62.5% with Q2M dosing25
  • UZEDY's unique pharmacokinetic profile attains therapeutic plasma concentrations within 6 to 24 hours of administration, with no loading dose or oral supplementation required, streamlining initiation26
*
Treatments consisted of mood stabilizers (primarily lithium and valproate), antidepressants, and/or anxiolytics. All oral antipsychotics were discontinued after the first 3 weeks after the initial injection of IM risperidone LAI.8

References
  1. Kane JM, Correll CU. Optimizing treatment choices to improve adherence and outcomes in schizophrenia. J Clin Psychiatry. 2019;80(5):IN18031AH1C.
  2. Alvarez-Jiminez M, Priede A, Hetrick SE, et al. Risk factors for relapse following treatment for first episode psychosis: a systematic review and meta-analysis of longitudinal studies. Schizophr Res. 2012;139(1-3):116-128.
  3. Nasrallah HA. 10 devastating consequences of psychotic relapses. Curr Psychiatry. 2021;20(5):9-12.
  4. Emsley R, Oosthuizen P, Koen L, et al. Comparison of treatment response in second-episode versus first-episode schizophrenia. J Clin Psychopharmacol. 2013;33(1):80-83.
  5. Takeuchi H, Siu C, Remington G, et al. Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology. 2019;44(6):1036-1042.
  6. Girardi P, Del Casale A, Rapinesi C, et al. Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate. Hum Psychopharmacol. 2018;33(3):e2658.
  7. American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. Washington, DC: American Psychiatric Association; 2021.
  8. Bera RB. Patient outcomes within schizophrenia treatment: a look at the role of long-acting injectable antipsychotics. J Clin Psychiatry. 2014:75(suppl 2):30-33.
  9. Correll CU, Martin A, Patel C, et al. Systematic literature review of schizophrenia clinical practice guidelines on acute and maintenance management with antipsychotics. Schizophrenia (Heidelb). 2022;8(1):5.
  10. American Association of Community Psychiatrists. Clinical Tip Series. Long Acting Antipsychotic Medications. Accessed February 23, 2026. http‌s://iss‌uu.co‌m/gapa‌rticles/docs/aacp_clinical_tip-laa_december_2017_/1
  11. Gardner KN, Nasrallah HA. Managing first-episode psychosis: rationale and evidence for nonstandard first-line treatments for schizophrenia. Curr Psychiatry. 2015;14(7):33-45.
  12. Kane JM, Agid O, Castle DJ, et al. The use of long-acting injectables for people with schizophrenia: consensus panel recommendations for overcoming barriers and implementing treatment. Neurol Ther. 2025;14(6):2551-2581.
  13. Weiden PJ, Roma RS, Velligan DI, et al. The challenge of offering long-acting antipsychotic therapies: a preliminary discourse analysis of psychiatrist recommendations for injectable therapy to patients with schizophrenia. J Clin Psychiatry. 2015;76(6):684-690.
  14. Lindenmayer JP, Glick ID, Talreja H, Underriner M. Persistent barriers to the use of long-acting injectable antipsychotics for the treatment of schizophrenia. J Clin Psychopharmacol. 2020;40(4):346-349.
  15. Medrano S, Abdel-Baki A, Stip E, Potvin S. Three-year naturalistic study on early use of long-acting injectable antipsychotics in first episode psychosis. Psychopharmacol Bull. 2018;48(4):25-61.
  16. Blackwood C, Sanga P, Nuamah I, et al. Patients' preference for long-acting injectable versus oral antipsychotics in schizophrenia: results from the patient-reported medication preference questionnaire. Patient Prefer Adherence. 2020;14:1093-1102.
  17. Caroli F, Raymondet P, Izard I, et al. Opinions of French patients with schizophrenia regarding injectable medication. Patient Prefer Adherence. 2011;5:165-171.
  18. Franzenburg KR, Hansen RT, Suett M, et al. Perspectives of psychiatrists and psychiatric nonphysicians on treating schizophrenia with long-acting injectable antipsychotics: subgroup analysis from the multinational ADVANCE study. Presented at: Annual Psych Congress Elevate; May 28-31, 2025; Las Vegas, NV.
  19. Miller WR, Rollnick S, eds. Motivational Interviewing: Helping People Change. 4th ed. The Guilford Press; 2023.
  20. Invega Sustenna® (paliperidone palmitate). Prescribing Information. Titusville, NJ: Janssen Pharmaceuticals, Inc.
  21. Risperdal Consta® (risperidone). Prescribing Information. Titusville, NJ: Janssen Pharmaceuticals, Inc.
  22. Abilify Maintena® (aripiprazole). Prescribing Information. Otsuka America Pharmaceutical, Inc.
  23. Abilify Asimtufii® (aripiprazole). Prescribing Information. Otsuka Pharmaceutical, Inc.
  24. Aristada® (aripiprazole lauroxil). Prescribing Information. Alkermes, Inc.
  25. Kane JM, Harary E, Eshet R, et al. Efficacy and safety of TV-46000, a long-acting, subcutaneous, injectable formulation of risperidone, for schizophrenia: a randomised clinical trial in the USA and Bulgaria. Lancet Psychiatry. 2023;10(12):934-943.
  26. UZEDY® (risperidone) extended-release injectable suspension Current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.
  27. Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
  28. Robinson DG, Suett M, Wilhelm A, et al. Patient and healthcare professional preferences for characteristics of long-acting injectable antipsychotic agents for the treatment of schizophrenia. Adv Ther. 2023;40(5):2249-2264.
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Expert Commentary

Addressing Barriers in Schizophrenia Management With LAIs and UZEDY

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Clinical Data

Evaluating Efficacy and Safety: A Data-Driven Review of UZEDY for Schizophrenia Treatment




INDICATION AND USAGE

UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION
WARNING: 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. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

INDICATIONS AND USAGE

UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION
WARNING: 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. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone.

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): TD, 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 predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown.

The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.

Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone.
Dyslipidemia has been observed in patients treated with atypical antipsychotics.
Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.

Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication.

Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm3) and follow their WBC until recovery.

Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely.

Seizures During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration.

Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention.

Body temperature regulation. Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions.

ADVERSE REACTIONS

The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.

The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule.

DRUG INTERACTIONS

  • Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone.
  • Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration.
  • Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.
  • UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.
  • UZEDY may antagonize the pharmacologic effects of dopamine agonists.
  • Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS)
USE IN SPECIFIC POPULATIONS

Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at h‌tt‌p:‌/‌/‌womensm‌entalhealth.‌org‌/‌clinical‌and-resear‌ch-progr‌ams‌/‌pregnancyregistry‌/.

Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS.

Fertility: UZEDY may cause a reversible reduction in fertility in females.

Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients.

Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY.

Patients with Parkinson's disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS.

Please see the accompanying full Prescribing Information for UZEDY, including Boxed WARNING.
INDICATIONS AND USAGE

UZEDY (risperidone) extended-release injectable suspension for subcutaneous use is indicated for the treatment of schizophrenia in adults.

IMPORTANT SAFETY INFORMATION
WARNING: 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. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

CONTRAINDICATIONS: UZEDY is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone.

WARNINGS AND PRECAUTIONS

Cerebrovascular Adverse Reactions: In trials of elderly patients with dementia-related psychosis, there was a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, in patients treated with oral risperidone compared to placebo. UZEDY is not approved for use in patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If NMS is suspected, immediately discontinue UZEDY and provide symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): TD, 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 predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown.

The risk of developing TD and the likelihood that it will become irreversible are believed to increase with the duration of treatment and the cumulative dose. The syndrome can develop, after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

If signs and symptoms of TD appear in a patient treated with UZEDY, drug discontinuation should be considered. However, some patients may require treatment with UZEDY despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.

Hyperglycemia and diabetes mellitus (DM), in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics, including risperidone. Patients with an established diagnosis of DM who are started on atypical antipsychotics, including UZEDY, should be monitored regularly for worsening of glucose control. Patients with risk factors for DM (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including UZEDY, should undergo fasting blood glucose (FBG) testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including UZEDY, should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics, including UZEDY, should undergo FBG testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone, was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of risperidone.
Dyslipidemia has been observed in patients treated with atypical antipsychotics.
Weight gain has been observed with atypical antipsychotic use. Monitoring weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, risperidone elevates prolactin levels and the elevation persists during chronic administration. Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents.

Orthostatic Hypotension and Syncope: UZEDY may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope. UZEDY should be used with particular caution in patients with known cardiovascular disease, cerebrovascular disease, and conditions which would predispose patients to hypotension and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of oral risperidone and antihypertensive medication.

Falls: Antipsychotics, including UZEDY, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other fall-related injuries. Somnolence, postural hypotension, motor and sensory instability have been reported with the use of risperidone. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotic agents, including risperidone. In patients with a pre-existing history of a clinically significant low white blood cell count (WBC) or absolute neutrophil count (ANC) or a history of drug-induced leukopenia or neutropenia, perform a complete blood count (CBC) frequently during the first few months of therapy. In such patients, consider discontinuation of UZEDY at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue UZEDY in patients with ANC < 1000/mm3) and follow their WBC until recovery.

Potential for Cognitive and Motor Impairment: UZEDY, like other antipsychotics, may cause somnolence and has the potential to impair judgement, thinking, and motor skills. Somnolence was a commonly reported adverse reaction associated with oral risperidone treatment. Caution patients about operating hazardous machinery, including motor vehicles, until they are reasonably certain that treatment with UZEDY does not affect them adversely.

Seizures During premarketing studies of oral risperidone in adult patients with schizophrenia, seizures occurred in 0.3% of patients (9 out of 2,607 patients), two in association with hyponatremia. Use UZEDY cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Antipsychotic drugs, including UZEDY, should be used cautiously in patients at risk for aspiration.

Priapism has been reported during postmarketing surveillance for other risperidone products. A case of priapism was reported in premarket studies of UZEDY. Severe priapism may require surgical intervention.

Body temperature regulation. Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral risperidone use. Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use UZEDY with caution in patients who experience these conditions.

ADVERSE REACTIONS

The most common adverse reactions with risperidone (≥5% and greater than placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.

The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule.

DRUG INTERACTIONS

  • Carbamazepine and other strong CYP3A4 inducers decrease plasma concentrations of risperidone.
  • Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors increase risperidone plasma concentration.
  • Due to additive pharmacologic effects, the concomitant use of centrally-acting drugs, including alcohol, may increase nervous system disorders.
  • UZEDY may enhance the hypotensive effects of other therapeutic agents with this potential.
  • UZEDY may antagonize the pharmacologic effects of dopamine agonists.
  • Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS)
USE IN SPECIFIC POPULATIONS

Pregnancy: May cause EPS and/or withdrawal symptoms in neonates with third trimester exposure. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including UZEDY, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at h‌tt‌p:‌/‌/‌womensm‌entalhealth.‌org‌/‌clinical‌and-resear‌ch-progr‌ams‌/‌pregnancyregistry‌/.

Lactation: Infants exposed to risperidone through breastmilk should be monitored for excess sedation, failure to thrive, jitteriness, and EPS.

Fertility: UZEDY may cause a reversible reduction in fertility in females.

Pediatric Use: Safety and effectiveness of UZEDY have not been established in pediatric patients.

Renal or Hepatic Impairment: Carefully titrate on oral risperidone up to at least 2 mg daily before initiating treatment with UZEDY.

Patients with Parkinson's disease or dementia with Lewy bodies can experience increased sensitivity to UZEDY. Manifestations and features are consistent with NMS.

Please see the accompanying full Prescribing Information for UZEDY, including Boxed WARNING.