Oral risperidone: Safety has been well characterized in adults with schizophrenia
The safety profile of UZEDY is expected to be similar to that of corresponding oral risperidone doses (2-5 mg daily)1
- Discontinuation rates across prior trials due to adverse events were approximately 4% of patients receiving placebo and 7% of patients treated with oral risperidone1
- Data from 2 fixed-dose clinical trials in adults with schizophrenia showed evidence of dose-relatedness for extrapyramidal symptoms associated with oral risperidone treatment1
- The most common adverse reactions (>5% and twice placebo) in three 4- to 8-week, double-blind, placebo-controlled trials of oral risperidone 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 pain1
Please see additional Important Safety Information, including Boxed WARNING, below.
Adverse Reactions in ≥2% of Oral
Risperidone–Treated Adult Patients
(and Greater Than Placebo) in Clinical Trials1
| SYSTEM/ORGAN CLASS ADVERSE REACTION |
2 MG TO 8 MG PER DAY % (N=366) |
>8 MG TO 16 MG PER DAY % (N=198) |
PLACEBO % (N=225) |
|---|---|---|---|
| Cardiac disorders | |||
| Tachycardia | 1 | 3 | 0 |
| Eye disorders | |||
| Vision blurred | 3 | 1 | 1 |
| Gastrointestinal disorders | |||
| Nausea | 9 | 4 | 4 |
| Constipation | 8 | 9 | 6 |
| Dyspepsia | 8 | 6 | 5 |
| Dry mouth | 4 | 0 | 1 |
| Abdominal discomfort | 3 | 1 | 1 |
| Salivary hypersecretion | 2 | 1 | <1 |
| Diarrhea | 2 | 1 | 1 |
| General disorders | |||
| Fatigue | 3 | 1 | 0 |
| Chest pain | 2 | 2 | 1 |
| Asthenia | 2 | 1 | <1 |
| Infections and infestations | |||
| Nasopharyngitis | 3 | 4 | 3 |
| Upper respiratory tract infection | 2 | 3 | 1 |
| Sinusitis | 1 | 2 | 1 |
| Urinary tract infection | 1 | 3 | 0 |
| Investigations | |||
| Blood creatine phosphokinase increased | 1 | 2 | <1 |
| Heart rate increased | <1 | 2 | 0 |
| Musculoskeletal and connective tissue disorders | |||
| Back pain | 4 | 1 | 1 |
| Arthralgia | 2 | 3 | <1 |
| Pain in extremity | 2 | 1 | 1 |
| Nervous system disorders | |||
| Parkinsonism* | 14 | 17 | 8 |
| Akathisia* | 10 | 10 | 3 |
| Sedation | 10 | 5 | 2 |
| Dizziness | 7 | 4 | 2 |
| Dystonia* | 3 | 4 | 2 |
| Tremor* | 2 | 3 | 1 |
| Dizziness postural | 2 | 0 | 0 |
| Psychiatric disorders | |||
| Insomnia | 32 | 25 | 27 |
| Anxiety | 16 | 11 | 11 |
| Respiratory, thoracic, and mediastinal disorders | |||
| Nasal congestion | 4 | 6 | 2 |
| Dyspnea | 1 | 2 | 0 |
| Epistaxis | <1 | 2 | 0 |
| Skin and subcutaneous tissue disorders | |||
| Rash | 1 | 4 | 1 |
| Dry skin | 1 | 3 | 0 |
| Vascular disorders | |||
| Orthostatic hypotension | 2 | 1 | 0 |
The efficacy and safety of UZEDY were evaluated in 542 patients with schizophrenia in the RISE trial2
- In the clinical trial, injection site pain was reported by 6% of patients treated with UZEDY2
- All injection site reactions (nodule, pruritus, erythema, mass, and swelling) were mild to moderate in severity with the exception of 1 case of severe pruritus, which resolved after 6 days1
- Injection site reactions were reported in 22 patients (13%) in the placebo group, 36 patients (20%) in the UZEDY Q1M group, and 37 patients (21%) in the UZEDY Q2M group1
- The most common injection site reactions listed in the Prescribing Information are nodule (7% in both the UZEDY Q1M and Q2M groups and 3% in the placebo group) and pruritus (5% and 3% in the UZEDY Q1M and Q2M groups, respectively, and 2% in the placebo group)1
Injection Site Reactions Occurring in ≥2% of Patients in RISE2†
| ADVERSE REACTION | UZEDY Q1M % (N=183) |
UZEDY Q2M % (N=180) |
PLACEBO % (N=179) |
|---|---|---|---|
| Injection site nodule | 7 | 7 | 3 |
| Injection site pruritus | 5 | 4 | 2 |
| Injection site erythema | 3 | 4 | 1 |
| Injection site mass | 2 | 3 | <1 |
| Injection site swelling | 1 | 2 | 0 |
The randomized withdrawal study design of RISE may have reduced the observed rate of adverse reactions with UZEDY
- Frequently occurring adverse events‡ were generally rated as mild or moderate in severity2
- Discontinuation rates due to adverse events across treatment arms were 11% of patients receiving placebo and 13% of patients receiving UZEDY2
Adverse Reactions Occurring in ≥2% of Patients in RISE2†
| ADVERSE REACTION | UZEDY Q1M % (N=183) |
UZEDY Q2M % (N=180) |
PLACEBO % (N=179) |
|---|---|---|---|
| Dyspepsia | 2 | <1 | 0 |
| Nasopharyngitis | 5 | 2 | 3 |
| Upper respiratory tract infection | 4 | 1 | 3 |
| Urinary tract infection | 4 | 4 | 2 |
| Weight increased | 5 | 7 | 3 |
| Increased appetite | 2 | 1 | 1 |
| Diabetes mellitus | 0 | 2 | 0 |
| Type 2 diabetes mellitus | 2 | <1 | 0 |
| Dizziness | 4 | 4 | <1 |
| Somnolence | 3 | 4 | <1 |
| Drooling | 0 | 2 | 0 |
| Extrapyramidal disorder | 5 | 4 | 0 |
| Tremor | 2 | 2 | 0 |
| Restlessness | 0 | 2 | 0 |
| Erectile dysfunction | <1 | 2 | 0 |
References: 1. UZEDY® (risperidone) extended-release injectable suspension Current Prescribing Information. Parsippany, NJ: Teva Neuroscience, Inc. 2. Data on file. Parsippany, NJ: Teva Neuroscience, Inc.
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administration & DOSING
UZEDY has flexible dosing options and is administered by a healthcare professional via subcutaneous injection.1
Administration & DosingINDICATION 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/clinical-and-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.
