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Volume 7

Clinical Data

Maintaining Plasma Levels in Schizophrenia Treatment: SteadyTeq™ and UZEDY

NOVEMBER 2026 | 9 MIN READ

UZEDY Clinical Data hero

Maintaining Clinical Plasma Levels of Antipsychotic Medication

Schizophrenia is a complex disorder that can profoundly alter a person’s thoughts, feelings, behavior, and ability to function.1 Schizophrenia relapse can have wide-reaching consequences on patients’ lives, including incarceration or homelessness, social or vocational effects, cognitive decline, or development of treatment resistance.1 For this reason, preventing relapse is a key goal in schizophrenia treatment, and maintaining consistent treatment with antipsychotics is an important part of reaching that goal.2,3 Long-acting injectables (LAIs) release medication gradually so that antipsychotic plasma concentrations stay consistently within therapeutic levels throughout the dosing interval.2,3

UZEDY: Risperidone Plus an Innovative Drug Delivery System

UZEDY is an LAI that utilizes the copolymer drug delivery technology SteadyTeq™ to deliver risperidone over the course of the dosing interval.4 After subcutaneous injection, an initial release of risperidone results in therapeutic plasma concentrations within 6 to 24 hours after injection.4 A depot forms at the site of injection that slowly releases the remaining risperidone over the course of the 1- or 2-month dosing interval (Figure 1).4,5


Figure 1. Plasma Levels of Active Drug With UZEDY

Figure 1. Plasma Levels of Active Drug With UZEDY
Switching From Paliperidone Palmitate Once-Monthly (PP1M) to UZEDY

Switching between antipsychotics may be potentially destabilizing if psychotic symptoms or clinically relevant adverse events occur.6 Clinician discretion determines if and when switching is clinically appropriate, based on factors that may include patient preference, scheduling convenience, and concerns about tolerability or symptom breakthrough.6 Switching from other long-acting injectables or molecules besides oral risperidone to UZEDY was not directly studied in clinical trials.

However, once a clinician has determined that it is clinically necessary to switch a patient from another LAI to UZEDY, it is important to consider the pharmacokinetics of other LAIs and UZEDY. To help inform potential dosing conversions and switch strategies, Teva Pharmaceuticals, Inc. conducted population pharmacokinetic (PopPK) modeling to simulate switches from PP1M to UZEDY.7

Pharmacokinetically comparable doses of oral risperidone, PP1M, and UZEDY were determined based on PopPK modeling.7 Figure 4 shows the comparable doses of these 3 treatment options. The highest available dose strength of UZEDY is comparable to 5 mg of oral risperidone.8 Note that when a clinician with a patient who has never taken risperidone is considering switching to UZEDY, tolerability should be established with oral risperidone before initiating treatment.8


Figure 4. Comparable Doses of Oral Risperidone, PP1M, and UZEDY

Figure 4. Comparable Doses of Oral Risperidone, PP1M, and UZEDY

Total active moiety (TAM) concentration-time profiles were simulated using published PopPK models for PP1M and UZEDY, with virtual populations of 5,000 patients. Simulations were performed to predict TAM pharmacokinetic exposures when switching to UZEDY Q1M or Q2M, 4 to 6 weeks at steady state after the last injection of PP1M.7

One switching strategy evaluated was a 1:1 steady-state, comparable-dose switch from PP1M to UZEDY Q1M or Q2M. This example switching simulation assessed patients receiving a 234-mg dose of PP1M who were switching to UZEDY 125 mg Q1M or UZEDY 250 mg Q2M. Based on the TAM concentration simulation, it was determined that patients switching to UZEDY in this scenario should be initiated 4 weeks after the last PP1M dose.7 These switching simulation data are a tool for clinicians to use when planning to switch a patient from PP1M to UZEDY, and can be used to help determine what is appropriate for an individual patient.

Efficacy and the Safety of UZEDY

In the RISE clinical trial, patients treated with UZEDY demonstrated a significant reduction in risk of relapse when compared with patients treated with placebo.9 UZEDY once monthly (Q1M) significantly reduced the risk of relapse by 80% compared with placebo, and UZEDY once every 2 months (Q2M) significantly reduced the risk of relapse by 62.5% compared with placebo (Figure 2).9


Figure 2. Significant Reduction in Risk of Relapse

Figure 2. Significant Reduction in Risk of Relapse

The safety of UZEDY was also evaluated in the RISE clinical trial.9 Figure 3 shows all adverse reactions that occurred in ≥2% of patients with schizophrenia in any treatment arm of UZEDY during the double-blind relapse prevention stage of the RISE trial.10


Figure 3. Adverse Reactions Occurring in ≥2% of Patients in RISE

Figure 3. Adverse Reactions Occurring in ≥2% of Patients in RISE

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.8

The most common injection site reactions with UZEDY (≥5% and greater than placebo) were pruritus and nodule. The systemic safety profile for UZEDY was consistent with the known safety profile of risperidone.8

Key Takeaways

UZEDY utilizes SteadyTeq™ technology to deliver risperidone, enabling rapid attainment of clinically relevant plasma levels that are maintained throughout a once-monthly or once-every-two-months dosing regimen.5 In the RISE study, UZEDY demonstrated a significant reduction in relapse risk compared to placebo, and the safety of UZEDY was evaluated.9 Additionally, PopPK modeling was employed to simulate the transition of patients from PP1M to UZEDY, providing clinicians with insights to determine how to initiate this switch in treatment.7


References
  1. Nasrallah HA. 10 devastating consequences of psychotic relapses. Curr Psychiatry. 2021;20(5):9-12.
  2. American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association; 2021.
  3. 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.
  4. Perlstein I, Merenlender Wagner A, Gomeni R, et al. Population pharmacokinetic modeling and simulation of TV-46000: a long-acting injectable formulation of risperidone. Clin Pharmacol Drug Dev. 2022;11(7):865-877.
  5. Merenlender Wagner A, Elgart A, Perlstein I, et al. Phase 1 open-label study assessing the pharmacokinetics and safety of TV-46000, a novel long-acting subcutaneous injectable formulation of risperidone. Presented at: European Congress of Neuropathology; October 2-5, 2021; Lisbon, Portugal. Poster P.0463.
  6. Højlund M, Correll CU. Switching to long-acting injectable antipsychotics: pharmacological considerations and practical approaches. Expert Opin Pharmacother. 2023;24(13):1463-1489.
  7. 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. Adv Ther. 2025;42(11):5564-5577.
  8. UZEDY® (risperidone) extended-release injectable suspension Current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.
  9. 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.
  10. Data on file [CSR]. Parsippany, NJ: Teva Neuroscience, Inc.
Previous

Therapeutic Considerations

One-Step Initiation and Relapse Reduction With UZEDY in Schizophrenia


INDICATIONS AND USAGE

UZEDY® (risperidone) extended-release injectable suspension for subcutaneous use is indicated in adults for the treatment of schizophrenia and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder.

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 in adults for the treatment of schizophrenia and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder.

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 on 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 in patients with schizophrenia (≥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 adverse reactions with risperidone in patients with bipolar disorder were weight increased (5% in monotherapy trial) and tremor and parkinsonism (≥10% in adjunctive therapy trial).

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 full Prescribing Information for UZEDY, including Boxed WARNING.
INDICATIONS AND USAGE

UZEDY® (risperidone) extended-release injectable suspension for subcutaneous use is indicated in adults for the treatment of schizophrenia and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder.

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 on 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 in patients with schizophrenia (≥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 adverse reactions with risperidone in patients with bipolar disorder were weight increased (5% in monotherapy trial) and tremor and parkinsonism (≥10% in adjunctive therapy trial).

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 full Prescribing Information for UZEDY, including Boxed WARNING.