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Volume 5

Therapeutic Considerations

Exploring Long-Acting Injectables as a Treatment Option for Bipolar I Disorder

DECEMBER 2025 | 8 MIN READ

women and doctor discussing treatment

Bipolar I Disorder (BD1) Is a Complex and Chronic Illness With the Potential for Relapse

BD1 is a complex and chronic mental health disorder characterized by fluctuations between manic and depressive episodes that can cause significant functional impairment and can result in hospitalization.1 BD1 is typically diagnosed in late adolescence or early adulthood after at least 5 years of symptoms, which can vary greatly among individuals, and is often accompanied by other psychiatric comorbidities, including anxiety and substance use disorders.1-3 The lifetime relapse rate of BD1 is up to 90%, with depressive or manic episodes often reoccurring within 2 years of the initial episode.4,5

Long-Acting Injectables (LAIs) Can Play a Role in the Treatment of BD1

Following treatment of acute mania, the goal is to prevent its relapse. Antipsychotics can be used as monotherapy or in combination with lithium or an anticonvulsant for the treatment of mania.1,6 Nonadherence to prescribed treatment is a predictor of relapse, but adherence can be difficult to assess in patients.7 LAI formulations of antipsychotics were designed to provide consistent blood concentrations over an extended period of time.2 Missed scheduled injections are also known to providers.7

UZEDY Is Approved for the Treatment of BD1

UZEDY® (risperidone) is FDA-approved as monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of BD1 in adults.8 The approval of UZEDY in BD1 was supported by model-informed drug development, which is an approach that leverages existing data in computational modeling and simulation methods to streamline the FDA-approval process.8-10 Population pharmacokinetic models were used to compare exposure levels of UZEDY with another risperidone LAI that was administered intramuscularly.10 Further, the established efficacy of IM risperidone LAI in trials of patients with BD1 was assessed using exposure-response modeling to extrapolate therapeutic equivalence of UZEDY.10 Finally, the safety of UZEDY in BD1 was determined using existing data for IM risperidone LAI in BD1.8

UZEDY makes use of an innovative drug delivery platform called SteadyTeqTM, to formulate an LAI antipsychotic that can be administered subcutaneously.11 Pharmacokinetic studies have demonstrated that following a single dose of UZEDY, therapeutic plasma concentrations are achieved within 6 to 24 hours and maintained throughout the dosing interval, without the need for oral supplementation or loading doses.11,12

UZEDY Offers Established Efficacy and Safety Profiles in BD1

The efficacy of UZEDY as monotherapy for the treatment of BD1 is based on a multicenter, randomized, double-blind, placebo-controlled study of IM risperidone LAI. 501 adults with BD1 initially entered an open-label phase where they received the IM risperidone LAI. After 26 weeks, 303 of the patients (60%) were judged to be stable and were randomized to receive either the same dose of this IM risperidone LAI or placebo. Time to relapse (depression, mania, hypomania, or mixed) was delayed in patients receiving monotherapy with monotherapy IM risperidone LAI (Figure 1).8


Figure 1. UZEDY Monotherapy Provides Delayed Time to Relapse

Figure 1

The efficacy of UZEDY as adjunctive treatment of BD1 is based on a multicenter, randomized, double-blind, placebo-controlled study of another risperidone LAI. 240 adults with BD1 were initially treated during an open-label period with the IM risperidone LAI as adjunctive therapy in addition to continuing their usual treatment for BD1.* After 16 weeks, 124 patients (52%) were judged to be stable and were randomized to double-blind treatment with either the same dose of the IM risperidone LAI or placebo, in addition to continuing their usual treatment. Time to relapse (depression, mania, hypomania, or mixed) was delayed in patients receiving adjunctive therapy with the IM risperidone LAI compared with placebo (Figure 2).8


Figure 2. Adjunctive Therapy With UZEDY Provides Delayed Time to Relapse

Figure 2

The safety profile of UZEDY as monotherapy for the maintenance treatment of BD1 in adults is based on adequate and well-controlled studies of the IM risperidone LAI. The safety of UZEDY is expected to be similar to that of the IM risperidone LAI.8

Figure 3 shows the most common adverse reactions reported with the IM risperidone LAI administered as monotherapy in a 24-month double-blind, placebo-controlled trial. Of the patients receiving the IM risperidone LAI, 0.6% discontinued due to an adverse reaction (hyperglycemia; n=1).8


Figure 3. Adverse Reactions Occurring in ≥2% of Patients With BD1 Receiving IM Risperidone LAI as Monotherapy

Figure 3

Figure 4 shows adverse reactions reported with the IM risperidone LAI administered as adjunctive therapy in a 52-week double-blind, placebo-controlled trial. Four percent of patients discontinued due to adverse reactions, compared with 1.5% of placebo-treated patients. Adverse reactions associated with discontinuation were hypokinesia (n=1) and tardive dyskinesia (n=1).8


Figure 4. Adverse Reactions Occurring in ≥4% Patients With BD1 Receiving Adjunctive Therapy With IM Risperidone LAI

Figure 4
Dosing and Administration Features of UZEDY

UZEDY can be started or restarted with a single injection. No loading dose or oral supplementation is required, resulting in streamlined initiation or reinitiation for patients who have missed their regularly scheduled dose.8,11 UZEDY is ready-to-use and comes in a single-dose prefilled syringe with a 5/8-inch, 21-gauge needle for subcutaneous injection in the abdomen or upper arm by a healthcare professional.11

UZEDY is available in 1-month dosing from initiation, with 3 dosage strengths, corresponding to 2 mg to 4 mg oral risperidone, allowing for treatment to be tailored to the individual needs of patients (Figure 5).11 Patients are not required to be stabilized on oral risperidone prior to initiating UZEDY, but tolerability should be established for patients who have never taken risperidone.8


Figure 5. UZEDY Dosing Interval and Dosing Strength Can Be Tailored to the Patient with BD1

Figure 5
Key Takeaways: UZEDY Delivers a Streamlined Administration of BD1 Treatment
  • Nonadherence to treatment is a predictor for relapse, which negatively impacts clinical outcomes for patients with BD17,13-15
  • LAIs provide consistent dosing within a given timeframe, and providers are aware of a missed scheduled injection2,7
  • With UZEDY, therapeutic plasma levels of risperidone are sustained throughout the dosing interval11,12
  • UZEDY may delay time to relapse in patients with BD1. Time to relapse was delayed in patients receiving the IM risperidone LAI used as monotherapy or adjunctive therapy8
  • The safety of risperidone LAIs has been well established in BD1, and the safety profile of UZEDY is expected to be similar8
  • The most common adverse events reported in trials of the IM risperidone LAI were increased weight (5% in a monotherapy trial) and tremor and Parkinsonism (≥10% in an adjunctive therapy trial)8
*
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. Carvalho AF, Firth J, Vieta E. Bipolar disorder. N Engl J Med. 2020;383(1):58-66.
  2. Vieta E, Tohen M, McIntosh D, Kessing LV, Sajatovic M, McIntyre RS. Early use of long-acting injectable antipsychotics in bipolar disorder type I: an expert consensus. Bipolar Disord. 2025;27(1):7-16.
  3. Cha B, Kim JH, Ha TH, Chang JS, Ha K. Polarity of the first episode and time to diagnosis of bipolar I disorder. Psychiatry Investig. 2009;6(2):96-101.
  4. Perlis RH, Ostacher MJ, Patel JK, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Am J Psychiatry. 2006;163(2):217-224.
  5. Tohen M, Zarate CA, Hennen J, et al. The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence. Am J Psychiatry. 2003;160(12):2099-2107.
  6. Butler M, Urosevic S, Desai P, et al. Treatment for bipolar disorder in adults: a systematic review. Comparative Effectiveness Review No. 208. (Prepared by the Minnesota Evidence-based Practice Center under Contract No. 290-2012-00016-I.) AHRQ Publication No. 18-EHC012-EF. Rockville, MD: Agency for Healthcare Research and Quality; August 2018.
  7. Jawad I, Watson S, Haddad PM, Talbot PS, McAllister-Williams RH. Medication nonadherence in bipolar disorder: a narrative review. Ther Adv Psychopharmacol. 2018;8(12):349-363.
  8. UZEDY® (risperidone) extended-release injectable suspension Current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.
  9. US Food and Drug Administration (FDA). Guidance Document. M15 General Principles for Model-Informed Drug Development. Updated November 6, 2024. Accessed August 28, 2025. http‌s://ww‌w.fda.g‌ov/‌med‌ia/‌1‌84‌747/‌down‌load.
  10. Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
  11. 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.
  12. Wagner AM, 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.
  13. Nasrallah HA. Brain damage from recurrent relapses of bipolar mania: a call for early LAI use. Current Psych. 2023;22(8):9-10,54.
  14. Jones S, Riste L, Barrowclough C, et al. Reducing relapse and suicide in bipolar disorder: practical clinical approaches to identifying risk, reducing harm and engaging service users in planning and delivery of care – the PARADES (Psychoeducation, Anxiety, Relapse, Advance Directive Evaluation and Suicidality) programme. Programme Grants Appl Res. 2018;6(6).
  15. Hamilton JE, Passos IC, de Azevedo Cardoso T, et al. Predictors of psychiatric readmission among patients with bipolar disorder at an academic safety-net hospital. Aust N Z J Psychiatry. 2016;50(6):584-593.
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Expert Commentary

Considerations for UZEDY in Patients With Bipolar I Disorder

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.