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VOLUME 1
KOL Commentary
Thought-Leader Commentary With Leslie Citrome, MD, MPH, and Amber Hoberg, MSN, APRN, PMHNP-BC
July 2024 | 5 min read

We interviewed 2 distinguished opinion leaders, Dr Leslie Citrome and Amber Hoberg, on the impact of relapse in schizophrenia and considerations regarding the use of long-acting injectables (LAI). They also discussed their experience with UZEDY® (risperidone), a subcutaneous LAI used to treat adult patients with schizophrenia.

The clinical course of schizophrenia is often characterized by recurrent relapses. What impact does schizophrenia have on patients' daily lives when left untreated?
Leslie Citrome

There are 2 types of patients with schizophrenia I have managed over the years. One type experiences relatively few relapses and hospitalizations. The second type has frequent relapses and spends a lot of time in intermediate and long-term care settings.1,2 The goal here is to be reintegrated back into the community, but they had suffered with frequent relapses over the years so that their functional deficits were profound and they needed a lot of assistance and ongoing support in terms of housing and potential employment.3,5

What are the biggest challenges you have encountered in treating patients with schizophrenia?
Leslie Citrome

Many of my patients are on an LAI because they weren't taking their medication on a daily basis.8 Sometimes this comes from just not understanding the illness. Patients don't understand why they need to stay on medication.5,7 Another struggle for my patients is that many of them want to live independently and lead successful lives.5 However, cognitive symptoms have worsened for those patients with frequent relapses, and they've lost their ability to function.3-5 Where we intervene in the course of illness to prevent those relapses is important.5,6

How have currently available LAIs impacted the way you treat schizophrenia?
Leslie Citrome

Many of my patients are on an LAI due to adherence issues. In the inpatient setting, there are reminders available to take the medicine. However, we did research in the 1990s on the rate of use of LAIs within the state hospital system of New York. In one particular hospital, the rate of LAI use was about 40% of all patients hospitalized.8 In my opinion, they probably thought it was helpful to use LAIs in the institutional setting and avoid daily medication struggles that invariably would occur in that setting. When patients are told about this option, they may be quite accepting and wonder why they weren’t told about it before. Once stabilized on an LAI, patients do not have to remember to take their medication on a daily basis.9 LAIs have been helpful for both situations where patients will not or cannot take their medicine.7 Overall, LAIs are an important option among the various antipsychotic formulations, and I think they should be discussed with patients more frequently.7,10

Leslie Citrome

I have implemented the use of LAIs in my practice and have found them to be successful. In a number of instances, I was able to put patients on an LAI which allowed them to maintain their functionality without having someone give them their medications or having to remember to take their medications.5,6,9 LAIs have also helped with decreasing the burden of care in my group home, as patients don’t need to be given the medication on a daily basis. So while no clinical studies have been done to look at these outcomes, they have been some of the reasons I consider LAIs for my patients. Additionally, in my experience, LAIs have curtailed aggressive episodes in some patients which require significant staff time to intervene and calm the patient down.11-13 LAIs have been shown to improve both positive and negative symptoms as well as the general pathology of schizophrenia,12,13 while reducing the risk of relapse.14

What are some benefits and considerations among the currently available LAIs?
Leslie Citrome

As would be expected with effective antipsychotic treatment, patients may be more able to work, live independently, cook for themselves, and even have meaningful relationships with their family.5 While no clinical studies have been done to look at these outcomes, they are important considerations when providing antipsychotic treatment, including LAIs, to my patients. One challenge is that many of my patients have a fear of needles.9 They’ve told me that the needles are too big or too long or they don’t want the needle going into their muscle. Modesty is also another consideration for my patients. Gluteal injections, for example, require you to expose quite a bit of skin and some of my patients don’t like that aspect of the treatment.9

Leslie Citrome

One important benefit is that if a patient is on an LAI and isn't doing well, you don't have to guess whether or not a patient is taking their medicine. You can look for other clues, such as treatment resistance or psychosocial stressors that might have contributed to their worsening.10 Currently available LAIs differ in a variety of ways that are important to me, the patient, and the injector. As a prescriber, I want the flexibility in terms of dosing interval and dosing strength to customize what is being prescribed to the individual.15 For many of my patients, the size of the needle can be important, as well as where the medication can be injected.15,16 The injection staff may appreciate something that is ready to use and that doesn't require reconstitution.15

What do you know about the subcutaneous LAI UZEDY? What has been your experience and what have you heard from your colleagues?
Leslie Citrome

UZEDY uses an innovative drug delivery system called SteadyTeq to release risperidone.13,14,17 Risperidone has probably been the most commonly used antipsychotic in schizophrenia, at least in the US today,18 and having the ability to match up the dose patients received with something you give every 1 or 2 months is beneficial.19 UZEDY also doesn't require reconstitution or oral supplementation, so it is prefilled and ready to use, and there is a dose that is appropriate for that individual person.19 It also has a small injection volume, so little polymer gets injected under the skin.19 The SteadyTeq technology releases the molecule over a sustained period of time, allowing for a 1- or 2-month injection interval.20 No loading dose or oral supplementation is required, and if you are unsure about how long this person will be in the setting that you're treating them in, then this is a helpful option.19

Leslie Citrome

I do all my own injections, and UZEDY can be administered in a timely fashion. It takes me seconds to whip it, inspect it, and inject it for my patients. I even had 1 patient who missed a dose of UZEDY, and I was able to administer it as soon as possible at an interim visit.19 I appreciate that the therapeutic plasma concentration is reached within 6 to 24 hours, with no requirement for an oral loading dose.19 The safety of UZEDY is consistent with oral risperidone in patients with schizophrenia.19

How do you envision incorporating UZEDY into your treatment of patients with schizophrenia?
Leslie Citrome

If my patients are on risperidone, I offer UZEDY as an option at any time in the treatment process. Because it is available subcutaneously, it gives me an opportunity to go back to the patients who have refused LAIs in the past and inform them that there is another option.9,15 Many of my patients have said they would consider UZEDY.21

How might UZEDY match the needs you and your patients look for in an LAI? What makes you excited about using UZEDY for your patients?
Leslie Citrome

All patients with schizophrenia should be made aware of the different formulations of antipsychotics available to them, including LAIs.15 UZEDY is an exciting option for my staff, patients, and me. For the staff, it is ready to use and no oral supplementation or reconstitution is necessary.19 It does not take long to prepare or administer this medication. For me, there are flexible dosing options available.19 For my patients, it is a short needle.19 It is also important that patients know about the clinical data behind LAIs, which informs us that the risk of relapse is reduced.10 LAIs can be offered successfully when information about them is presented in a positive way, using motivational interviewing techniques.15

Please see Indication and Important Safety Information below.

This newsletter is produced by Teva Pharmaceuticals, and Dr Leslie Citrome and Amber Hoberg were compensated by Teva for their insights.

References: 1. Jobe TH, Harrow M. Can J Psychiatry. 2005;50(14):892-900. 2. Lavaud P et al. Psychiatry Res. 2022;308:114339. 3. Gardner KN, Nasrallah HA. Curr Psychiatry. 2015;14(7):33-45. 4. Lin D et al. Front Psychiatry. 2021;12:695672. 5. Pietrini F et al. Neuropsychiatr Dis Treat. 2019;15:1045-1060. 6. Kaplan G et al. Patient Prefer Adherence. 2013;7:1171-1180. 7. Kane JM, Correll CU. J Clin Psychiatry. 2019;80(5):IN18031AH1C. 8. Citrome L et al. Psychopharmacol Bull. 1996;32(3):321-326. 9. Blackwood C et al. Patient Prefer Adherence. 2020;14:1093-1102. 10. Citrome L. Expert Rev Neurother. 2017;17(10):1029-1043. 11. Mohr P et al. Int J Clin Pract. 2017;71(9):10.1111. 12. Kane JM, Correll CU et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX. 13. Data on file. Parsippany, NJ: Teva Neuroscience, Inc. 14. Kane JM, Harary E et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX. 15. Citrome L. CNS Spectr. 2021;26(2):118-129. 16. Robinson DG et al. Adv Ther. 2023;40:2249-2264. 17. Merenlender Wagner A, Elgart A et al. Presented at: European Congress of Neuropathology; October 2-5, 2021; Lisbon, Portugal. 18. Kane JM, Mychaskiw MA et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX. 19. UZEDY Prescribing Information. Teva Neuroscience, Inc; 2023. 20. Perlstein I et al. Clin Pharmacol Drug Dev. 2022;11(7):865-877. 21. Robinson DG et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX.


Suggested Reading:

Blackwood C et al. Patient Prefer Adherence. 2020;14:1093-1102.

Citrome L et al. Psychopharmacol Bull. 1996;32(3):321-326.

Citrome L. Expert Rev Neurother. 2017;17(10):1029-1043.

Citrome L. CNS Spectr. 2021;26(2):118-129.

Gardner KN, Nasrallah HA. Curr Psychiatry. 2015;14(7):33-45.

Jobe TH, Harrow M. Can J Psychiatry. 2005;50(14):892-900.

Kaplan G et al. Patient Prefer Adherence. 2013;7:1171-1180.

Kane JM, Correll CU. J Clin Psychiatry. 2019;80(5):IN18031AH1C.

Kane JM, Harary E et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX.

Kane JM, Mychaskiw MA et al. Presented at: Psych Congress 2021; October 29-November 1, 2021; San Antonio, TX.

Perlstein I et al. Clin Pharmacol Drug Dev. 2022;11(7):865-877.

Pietrini F et al. Neuropsychiatr Dis Treat. 2019;15:1045-1060.

Robinson DG et al. Adv Ther. 2023;40:2249-2264.

UZEDY Prescribing Information. Teva Neuroscience, Inc; 2023.

INDICATION AND USAGE

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

IMPORTANT SAFETY INFORMATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

INDICATION AND USAGE

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

IMPORTANT SAFETY INFORMATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

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

WARNINGS AND PRECAUTIONS

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

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

Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown.

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

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

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

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

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

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

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

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

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

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

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

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

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

ADVERSE REACTIONS

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

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

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

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

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

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

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

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

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

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

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

IMPORTANT SAFETY INFORMATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. UZEDY is not approved for use in patients with dementia-related psychosis and has not been studied in this patient population.

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

WARNINGS AND PRECAUTIONS

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

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

Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause TD is unknown.

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

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

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

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

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

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

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

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

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

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

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

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

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

ADVERSE REACTIONS

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

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

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

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

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

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

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

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

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

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