In this interview, Ilan Melnick, MD, and Chelsie Monroe, MSN, APN, PMHNP-BC, discuss key considerations for selecting, initiating, and switching patients to long-acting injectables (LAIs), including UZEDY, for the treatment of schizophrenia.
Navigating LAI Selection, Initiation, and Switching to UZEDY
NOVEMBER 2026 | 12 MIN READ
To start us off, can you tell us a bit about the role of LAIs in schizophrenia treatment, and what you consider the most important factors when selecting one?
One of the challenges we run into in schizophrenia is that patients’ brains start to deteriorate early. Every relapse contributes to brain tissue loss and loss of functioning, which is why using LAIs to maintain consistent, predictable blood levels of medication and prevent relapse is so important.
When it comes to LAIs, one of the most important factors is the pharmacokinetics of the drug. Fewer than half of patients with schizophrenia take oral medications as prescribed, so our expected outcome and our observed outcome often diverge. With an LAI, we are aware if a patient has missed an injection because we administer it in our clinics, and we know that if we give an LAI with a one- or two-month dosing interval, the patient has received treatment for that period.
When I’m selecting an LAI, I first consider the molecule and whether it can provide the efficacy I’m looking for. Equally important are the practical features that may affect the patient’s experience.
I consider factors such as needle size, injection frequency and volume, and potential side effects. Together, these considerations help me determine which treatment may be appropriate for each patient.
In your experience, what are some of the challenges that come with discussing LAIs with your patients?
Many patients with schizophrenia lack insight into their illness and may object to taking a medication at all, so when it comes to discussing treatments, I often bring family members and caregivers into the conversation to help. I also try to talk to patients about their goals. Building that alliance, not just with the patient, but also with caregivers, matters. Using an open-ended, motivational-interviewing approach and focusing on the patient’s challenges rather than ours, goes a long way toward getting a patient to consider an LAI early.
Many patients are also concerned about the physical experience of getting the injection itself. In my office, we give about 20 injections a week, and one of the most common complaints is discomfort from injecting into muscle tissue, and larger injection volumes can make that worse. Talking openly with patients about injection volume, needle size, and injection-site placement plays a big role in getting patients to try an LAI.
From a practical standpoint, how do initiation requirements—like needing multiple injections to reach therapeutic levels or oral supplementation—affect your decision to use an LAI?
Historically in psychiatry, even switching directly from an oral treatment to an LAI formulation of the same molecule has come with a list of steps to bridge patients up to a therapeutic level—things like loading doses or oral supplementation. These days, there are LAIs available that don’t require these steps, and that can be helpful, especially for patients with schizophrenia who may miss an appointment and need to reinitiate treatment. And even if a patient misses an appointment, they can come in anytime and get their injection without needing a second shot or oral supplementation to reinitiate treatment.
What I like about UZEDY is that patients reach therapeutic blood levels within 6 to 24 hours, and these levels are maintained throughout the dosing interval, which means that patients can be stabilized and discharged more quickly. Patients also don’t need to return a week later for a second injection, so we can focus on coordinating with the patient and their caregivers for their one-month appointment.
Beyond the easy initiation or reinitiation, what other features of UZEDY are important?
We both work in settings where you’re not always sure a patient will come back, so the dosing flexibility of UZEDY can be an important feature. I can give my patient a 1- or 2-month dose of UZEDY and know that clinical plasma levels are maintained for the full dosing interval. I often use the 2-month dosing option for patients who need that flexibility, like my unhoused patients, or who may just want a longer interval between doses.
I would also add that patients, especially my patients that don’t like needles, appreciate that UZEDY comes as a subcutaneous injection that can be administered in the back of the arm or the abdomen. And from the clinician perspective, initiation is streamlined. It also comes in a pre-filled syringe, and can be stored at room temperature for 90 days.
For clinicians who are considering switching a patient from another LAI to UZEDY, what clinical or logistical factors are most important in that decision?
If I’m going to make a switch, I always consider the risk of decompensation first. I also think about whether there are any side effects of the new medication that I’d need to manage. And I always ask: Is there strong, clinical support for making this change? I challenge myself and my patients to think about the advantages and disadvantages based on factors such as the patient’s preference and goals, scheduling convenience, and concerns about tolerability or symptom breakthrough.
I'd also like to add that we should really challenge ourselves to question what "stable" really means. If a patient is doing well, we may be hesitant to make any changes. However, we should still thoughtfully consider what can be improved, focusing not just on symptom improvement, but also the patient’s goals.
I agree, and I’ll add that once you’ve established that a change is warranted, it’s important to understand how to switch a patient to another treatment. Teva has produced population PK data that can be used as one tool for determining how to switch a patient to UZEDY from another LAI. They have popPK data for example, that reflect one possible simulation for switching patients from PP1M to UZEDY while maintaining plasma levels. From there, you can use your clinical discretion to adjust your treatment to the individual needs of your patient.
What advice would you give to colleagues who are hesitant to start patients on an LAI like UZEDY?
It’s our responsibility to know all the LAI options that are currently available and their key features. Maybe a patient simply doesn’t want an intramuscular injection, or maybe they would prefer a longer dosing interval. Our goal is to prevent relapses, and we need to know what tools are at our disposal to do that.
That’s exactly right. LAIs are underutilized in schizophrenia, and clinicians’ preconceptions play a role in that. Many of us were trained to think of LAIs as a last resort, but an expert consensus panel supports using LAIs as early as possible in the disease course.1 We need to do a better job training the next generation of clinicians on the full range of what’s available and what has changed in schizophrenia treatment.
I would challenge our colleagues to consider an LAI for all of our patients. In my opinion, LAIs shouldn't just be a preference, they should be the standard of care, and we should be working harder at training new clinicians about the treatment options available to them.
What are you looking forward to in the LAI space, and what do you hope will change in the next few years to improve outcomes for your patients?
Having long-acting formulations available across more of the molecules that are used to treat schizophrenia, particularly the ones clinicians use the most, would be a huge step forward for the field.
It’s about meeting patients’ needs. Some molecules may be appropriate for one patient and may not be appropriate for another. The goal isn't to replace one option with the other; it's to have multiple options available so that we can match the treatment to the appropriate patient.
Exactly. Schizophrenia treatment has evolved since LAIs were first introduced, and it continues to evolve. My hope is that clinicians will continue to learn about the options that are available to them and continue to involve caregivers and patients throughout the treatment process. We should use all the tools available to us to continue to improve outcomes for our patients with schizophrenia.
Key Takeaways
- The consistent plasma levels of antipsychotic that are delivered by LAIs may help prevent relapse and its potential consequences
- Efficacy and features such as needle size, injection volume, dosing frequency, and side effects are important to clinicians and patients when selecting an LAI
- Effective LAI conversations involve caregivers, motivational interviewing, and addressing patients' concerns about the injection itself
- Switching decisions should combine tools like popPK data with clinical judgment
- Despite guidelines favoring earlier LAI use,1 they remain underutilized; education about available LAIs and their features is important for increasing LAI use in schizophrenia treatment
Suggested Reading
- Kane JM, Agid O, Castle DJ, et al. The use of long-acting injectables for people with schizophrenia: consensus panel recommendations for overcoming barriers and implementing treatment. Neurol Ther. 2025;14:2551-2581.
- Nasrallah HA. 10 devastating consequences of psychotic relapses. Curr Psychiatry. 2021;20(5):9-12.
- 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.
- Martin A, Bessonova L, Hughes R, et al. Systematic review of real-world treatment patterns of oral antipsychotics and associated economic burden in patients with schizophrenia in the United States. Adv Ther. 2022;39(9):3933-3956.
- Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre-post studies. Lancet Psychiatry. 2021;8(5):387-404.
- 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.
- American Psychiatric Association. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association; 2021.
- Miller WR, Rollnick S, eds. Motivational Interviewing: Helping People Change. 4th ed. The Guilford Press; 2023.
- Gardner KN, Nasrallah HA. Managing first-episode psychosis: rationale and evidence for nonstandard first-line treatments for schizophrenia. Curr Psychiatry. 2015;14(7):33-45.
- Citrome L. Long-acting injectable antipsychotics update: lengthening the dosing interval and expanding the diagnostic indications. Expert Rev Neurother. 2017;17(10):1029-1043.
- 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.
- UZEDY® (risperidone) extended-release injectable suspension Current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc.
- 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.
- Højlund M, Correll CU. Switching to long-acting injectable antipsychotics: pharmacological considerations and practical approaches. Expert Opin Pharmacother. 2023;24(13):1463-1489.
- 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.
- Kane JM, Mychaskiw MA, Lim S, Suett M, Tian M, Rubio JM. Treatment journey from diagnosis to the successful implementation of a long-acting injectable antipsychotic agent in young adults with schizophrenia. J Clin Psychiatry. 2023;84(3):22m14544.
- Citrome L. Choosing among the long-acting injectable antipsychotics: an evidence-based pragmatic guide. CNS Spectr. 2025;30(1):e73. Erratum in: CNS Spectr. 2025;30(1):e84.
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.