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Volume 4

KOL Commentary

Considerations for UZEDY in Different Clinical Settings

August 2025 | 9 min read


In this interview, Dr M. Bryce Reynolds discusses the role of long-acting injectables (LAIs), including UZEDY, in the treatment of schizophrenia.

What role do LAI antipsychotics play in the treatment of patients with schizophrenia?
Jonathan M. Meyer, MD

I am a passionate advocate for LAIs in the treatment of schizophrenia, as they have been shown to prevent relapse in these patients.

LAIs allow clinicians to track patient injections and intervene if a dose is missed. This enables the care team to focus on aspects of the patient's disorder beyond daily medication adherence during appointments.

In my experience, LAIs help to fundamentally shift the paradigm of treating patients with schizophrenia from reactive daily supervision to proactive management.

However, LAIs are often underutilized in the treatment of patients with schizophrenia.

LAIs allow clinicians to track injections and intervene if a dose is missed, which may help enable them to focus on aspects of the patient's disorder beyond daily medicationadherence during appointments.
How do you approach the conversation with patients about LAIs? What steps do you take to encourage patients to express their preferences when selecting an LAI?
Jonathan M. Meyer, MD

Patients may have concerns or misconceptions about these treatments, so team members—including case managers, nurses, and therapists—who have built trust with these patients can present LAIs in the context of the overall clinical management of their schizophrenia.

I avoid telling patients that treatments will prevent hospitalization or end delusions, as this conflicts with their experiences. Instead, we focus on understanding what works for our patients and what they prefer. We motivate them by addressing their feelings, like anger or fear, that impact daily life and goals. Shared decision-making empowers patients and encourages them to consider new treatments.

Our clinic advocates for the earlier introduction of LAIs, including them in the same conversation as oral medications to integrate them naturally into the patient's treatment options.

Our clinic advocates for the earlier introduction of LAIs, including them in the same conversation as oral medications.
What makes UZEDY different from other LAIs?
Jonathan M. Meyer, MD

UZEDY, which is approved for adults with schizophrenia, contains risperidone—a drug familiar to many healthcare professionals (HCPs) and patients. The active metabolite of risperidone, paliperidone, is also familiar to psychiatry HCPs. What makes UZEDY different is that it uses innovative technology to deliver risperidone to our patients.

What features do you consider when choosing an LAI?
Jonathan M. Meyer, MD

The first features I consider are the efficacy and safety. UZEDY has a demonstrated efficacy and safety profile consistent with the well-established profile of oral risperidone. Additionally, there are several other features that providers and patients may consider when choosing an LAI.

I also consider the pharmacokinetic (PK) profile. Clinicians often consider how rapidly a drug can reach therapeutic concentrations and how long it takes to reach steady state.

In PK studies, UZEDY reached therapeutic levels within 6 to 24 hours of a single injection, and clinically relevant plasma levels were maintained throughout the 1- or 2-month dosing interval. Furthermore, UZEDY approaches steady-state levels within 2 months of initiation.

Due to its PK profile, UZEDY has no need for oral supplementation or a loading dose, resulting in a streamlined initiation and reinitiation process with a single dose.

Another factor I consider is the dosing frequency and available strengths. UZEDY offers the choice of either 1- or 2-month dosing from initiation with 4 available strengths, allowing treatment to be tailored to the individual patient.

Lastly, my patients are often concerned about the injection itself, including needle size and injection location. UZEDY is administered subcutaneously in the arm or abdomen using a short 5/8-inch, 21-gauge needle. When I discuss this with patients, I also explain potential injection site reactions (ISRs) with UZEDY, the majority of which were mild to moderate in the RISE study. Overall, ISRs decreased in frequency after the first injection and led to treatment discontinuations in 2% of patients in either treatment group. The most common ISRs with UZEDY (≥5% and greater than placebo) were pruritus and the development of a nodule.

In PK studies, UZEDY reached therapeutic levels within 6 to 24 hours of a single injection, and clinically relevant plasma levels were maintained throughout the 1- or 2-month dosing interval. Furthermore, UZEDY approaches steady-state levels within 2 months of initiation.
How do you discuss UZEDY with patients who have previously refused an LAI?
Jonathan M. Meyer, MD

Patients refuse LAIs for several reasons, and I try to understand what is motivating their decision. For example, I commonly encounter objections from patients who do not want to be controlled or who have had past experiences receiving injections in the emergency department as an acute treatment for agitation or psychosis. I will explain that UZEDY is not a sedative and that while we encourage trying a different medication, they have the option to stop if it doesn't meet expectations.

In cases where the patient is hesitant about the injection, I will often show my patients the needle. After seeing it and learning about the small injection volume (maximum 0.7 mL), some of these patients say they may be open to trying UZEDY.

In cases where the patient is hesitant about the injection, I will often show my patients the needle.
What role does UZEDY play in the treatment of patients across settings of care?
Jonathan M. Meyer, MD

Hospitalization and crisis unit admissions due to relapse are common occurrences for patients with schizophrenia, who need, upon discharge, to continue care in the outpatient setting. Because of the streamlined initiation of UZEDY, a patient in the hospital can be discharged after receiving 1 injection.

The option for a 1- or 2-month dosing interval with UZEDY is a key consideration when thinking about how the patient will transition between care settings. Often, there can be a delay between the patient’s discharge and their first outpatient appointment with a provider.

In my experience, the delay can be 5 to 6 weeks, and even if a patient has an appointment within the first month post discharge, they often miss that first appointment. Thus, if a patient receives an LAI with a 2-month dosing interval, like UZEDY, before discharge, the patient should maintain consistent levels of medication during the transition and can hopefully be seen before they miss a dose.

The option for a 1- or 2-month dosing interval with UZEDY is a key consideration when thinking about how the patient will transition between care settings. Often, there can be a delay between the patient’s discharge and their first outpatient appointment with a provider.
There may be some situations where a patient may need to switch therapies. How do you approach switching a patient to UZEDY?
Jonathan M. Meyer, MD

It’s up to the clinician’s discretion if and when switching is clinically appropriate. With that said, the decision is partly based on patient preference, scheduling convenience, or concerns about tolerability or symptom breakthrough. For instance, if a patient is already on an LAI but would like a less frequent dosing interval, that may warrant a discussion about switching.

When switching a patient to UZEDY, it’s important to start at a dose that is pharmacokinetically comparable to their current antipsychotic. Although the FDA provides no specific guidelines and clinical trials didn't study switching from other LAIs to UZEDY, population PK modeling has been conducted to simulate dosing conversions. I advise colleagues to review these data and use their clinical experience to determine a suitable starting dose of UZEDY.

What key message would you like to emphasize as the most important takeaway from our discussion today?
Jonathan M. Meyer, MD

I would just like to reiterate that I am a strong proponent of the early introduction of LAIs. We’ve discussed a number of features that may apply to different patient types or clinical settings, and introducing LAIs early in a patient’s treatment journey allows me and other staff to discuss LAIs in the context of their overall treatment. My goal is to ensure that my patients are offered an LAI as part of a comprehensive discussion about their treatment options so that they can contribute to shared decision-making about their treatment.

Key Takeaways:
  • LAIs allow clinicians to track injections and intervene if a dose is missed
  • UZEDY is different from other LAIs because it uses innovative technology to deliver risperidone to patients
  • In addition to the established efficacy and safety of UZEDY, the streamlined initiation, 1- or 2-month dosing options, needle size and options for subcutaneous injection in the back of the arm or abdomen are features to consider when selecting an LAI
  • Clinicians determine when it is appropriate to switch their patients from an LAI to UZEDY, and population PK modeling data can help them determine a starting dose
References

American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia.3rd ed. Washington, DC: American Psychiatric Association; 2021.

Correll CU, Citrome L, Haddad PM, et al. The use of long‑acting injectable antipsychotics in schizophrenia: evaluating the evidence. J Clin Psychiatry. 2016;77(suppl 3):1‑24.

Correll CU, Kane JM, Suett M, et al. Efficacy and safety of TV‑46000, subcutaneous long‑acting risperidone, by injection site (upper arm/abdomen): post hoc analysis of the RISE study. Presented at: Psych Congress; October 29‑November 1, 2021; San Antonio, TX.

Citrome L. Long‑acting injectable antipsychotics update: lengthening the dosing interval and expanding the Højlund M, Correll CU. Switching to long‑acting injectable antipsychotics: pharmacological considerations and practical approaches. Expert Opin Pharmacother. 2023;24(13):1463‑1489.

Kane JM, Correll CU. Optimizing treatment choices to improve adherence and outcomes in schizophrenia. J Clin Psychiatry. 2019;80(5):IN18031AH1C.

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.

Kurdyak P, Vigod SN, Newman A, et al. Impact of physician follow‑up care on psychiatric readmission rates in a population‑based sample of patients with schizophrenia. Psychiatr Serv. 2018;69(1):61‑68

Lindenmayer JP, Glick ID, Talreja H, et al. Persistent barriers to the use of long‑acting injectable antipsychotics for the treatment of schizophrenia. J Clin Psychopharmacol. 2020;40(4):346‑349.

Marcus SC, Chuang CC, Ng‑Mak DS, et al. Outpatient follow‑up care and risk of hospital readmission in schizophrenia and bipolar disorder. Psychiatr Serv. 2017;68(12):1239‑1246.

Masand PS, Roca M, Turner MS, et al. Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia: a review. Prim Care Companion J Clin Psychiatry. 2009;11(4):147‑154.

Perlstein I, Merenlender Wagner A, Elgart A, et al. Population pharmacokinetic modeling of TV‑46000, a risperidone long‑acting subcutaneous antipsychotic for the treatment of patients with schizophrenia. Neurol Ther. 2025;14(3):829‑848.

Perlstein I, Meyer J, Yue Z, et al. Switching patients with schizophrenia from intramuscular paliperidone palmitate once monthly to TV‑46000, a long‑acting subcutaneous antipsychotic: population pharmacokinetic‑based strategies. Presented at: Psych Congress Elevate; May 30‑June 2, 2024; Las Vegas, NV.

Rose B, Harvey PD. Anosognosia in schizophrenia. CNS Spectr. 2024;30(1):e24.

UZEDY® (risperidone) extended‑release injectable suspension current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.

Next

Therapeutic Considerations

Clinical Considerations When Switching Patients With Schizophrenia to UZEDY

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.

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.

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.
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.

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.