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Indications
Risperidone for Extended-Release Injectable Suspension is an atypical antipsychotic indicated: for the treatment of schizophrenia. ( 1.1 ) as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder. ( 1.2 )
1.1Schizophrenia Risperidone for Extended-Release Injectable
Suspension is indicated for the treatment of schizophrenia [see Clinical Studies ( 14.1 )] .
1.2Bipolar Disorder Risperidone for Extended-Release Injectable
Suspension is indicated as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder [see Clinical Studies ( 14.2 , 14.3 )] .
Contraindications
Risperidone for Extended-Release Injectable Suspension is contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the Risperidone for Extended-Release Injectable Suspension formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone.
Paliperidone is a metabolite of risperidone. Known hypersensitivity to risperidone, paliperidone, or to any excipients in Risperidone for Extended-Release Injectable Suspension. ( 4 )
Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis. Risperidone for Extended-Release Injectable Suspension is not approved for use in patients with dementia-related psychosis ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring ( 5.3 ) Tardive Dyskinesia: Discontinue treatment if clinically appropriate ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk.
These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. ( 5.5 ) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. ( 5.5 ) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.5 ) Weight Gain: Significant weight gain has been reported.
Monitor weight gain. ( 5.5 ) Hyperprolactinemia: Risperidone treatment may elevate prolactin levels. Long-standing hyperprolactinemia, when associated with hypogonadism, can lead to decreased bone density in men and women. ( 5.6 ) Orthostatic hypotension: associated with dizziness, tachycardia, bradycardia, and syncope can occur, especially during initial dose titration with oral risperidone. Use caution in patients with cardiovascular disease, cerebrovascular disease, and conditions that could affect hemodynamic responses.
( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics, including Risperidone for Extended-Release Injectable Suspension. Patients with history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood cell count (CBC) monitored frequently during the first few months of therapy and discontinuation of Risperidone for Extended-Release Injectable Suspension should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
( 5.9 ) Potential for cognitive and motor impairment: has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery, including automobiles. ( 5.10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. ( 5.11 ) Dysphagia: Esophageal dysmotility and aspiration can occur. Use cautiously in patients at risk for aspiration pneumonia.
( 5.12 ) Priapism: has been reported. Severe priapism may require surgical intervention. ( 5.13 ) Avoid inadvertent administration into a blood vessel. ( 5.15 )
5.1Increased 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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Risperidone for Extended-Release Injectable Suspension is not approved for the treatment of dementia-related psychosis [see Boxed Warning ] .
5.2Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73 to 97) in trials of oral risperidone in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with oral risperidone compared to patients treated with placebo.
Risperidone for Extended-Release Injectable Suspension is not approved for the treatment of patients with dementia-related psychosis [See also Boxed Warning and Warnings and Precautions ( 5.1 )].
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 Risperidone for Extended-Release Injectable Suspension and provide symptomatic treatment and monitoring.
5.4Tardive Dyskinesia
Tardive dyskinesia, 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 tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible 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 of treatment. Tardive dyskinesia 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. Given these considerations, Risperidone for Extended-Release Injectable Suspension should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients: (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.
In patients who do require chronic treatment, the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment. If signs and symptoms of tardive dyskinesia appear in a patient treated with Risperidone for Extended-Release Injectable Suspension, drug discontinuation should be considered. However, some patients may require treatment with Risperidone for Extended-Release Injectable Suspension despite the presence of the syndrome.
5.5Metabolic 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 Hyperglycemia and diabet
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Interactions
The interactions of Risperidone for Extended-Release Injectable Suspension with coadministration of other drugs have not been systematically evaluated. The drug interaction data provided in this section is based on studies with oral risperidone. Due to CNS effects, use caution when administering with other centrally-acting drugs. Avoid alcohol. ( 7.1 ) Due to hypotensive effects, hypotensive effects of other drugs with this potential may be enhanced.
( 7.2 ) Effects of levodopa and dopamine agonists may be antagonized. ( 7.3 ) Cimetidine and ranitidine increase the bioavailability of risperidone. ( 7.5 ) Clozapine may decrease clearance of risperidone. ( 7.7 ) Fluoxetine and paroxetine increase plasma concentrations of risperidone. ( 7.12 ) Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. ( 7.13 )
7.1Centrally-Acting Drugs and Alcohol Given
the primary CNS effects of risperidone, caution should be used when Risperidone for Extended-Release Injectable Suspension is administered in combination with other centrally-acting drugs or alcohol.
7.2Drugs with Hypotensive Effects Because
of its potential for inducing hypotension, Risperidone for Extended-Release Injectable Suspension may enhance the hypotensive effects of other therapeutic agents with this potential.
7.3Levodopa and Dopamine Agonists Risperidone for Extended-Release Injectable
Suspension may antagonize the effects of levodopa and dopamine agonists.
7.4Amitriptyline
Amitriptyline did not affect the pharmacokinetics of risperidone or of risperidone and 9-hydroxyrisperidone combined following concomitant administration with oral risperidone.
7.5Cimetidine and Ranitidine Cimetidine
and ranitidine increased the bioavailability of oral risperidone by 64% and 26%, respectively. However, cimetidine did not affect the AUC of risperidone and 9-hydroxyrisperidone combined, whereas ranitidine increased the AUC of risperidone and 9-hydroxyrisperidone combined by 20%.
7.6Methylphenidate
Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS). Monitor for symptoms of EPS with concomitant use of Risperidone for Extended-Release Injectable Suspension and methylphenidate [see Adverse Reactions (6.2)] .
7.7Clozapine
Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.
7.8Lithium
Repeated doses of oral risperidone (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (C max ) of lithium (N=13).
7.9Valproate
Repeated doses of oral risperidone (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (N=21). However, there was a 20% increase in valproate peak plasma concentration (C max ) after concomitant administration of oral risperidone.
7.10Digoxin
Oral risperidone (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin.
7.11Topiramate
Oral risperidone administered at doses from 1 to 6 mg/day concomitantly with topiramate 400 mg/day resulted in a 23% decrease in risperidone C max and a 33% decrease in risperidone AUC 0-12 hour at steady state. Minimal reductions in the exposure to risperidone and 9-hydroxyrisperidone combined, and no change for 9-hydroxyrisperidone were observed. This interaction is unlikely to be of clinical significance. There was no clinically relevant effect of oral risperidone on the pharmacokinetics of topiramate.
7.12Drugs That Inhibit CYP 2D6 and Other CYP Isozymes
Risperidone is metabolized to 9-hydroxyrisperidone by CYP 2D6, an enzyme that is polymorphic in the population and that can be inhibited by a variety of psychotropic and other drugs [see Clinical Pharmacology ( 12.3 )] . Drug interactions that reduce the metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower the concentrations of 9-hydroxyrisperidone. Analysis of clinical studies involving a modest number of poor metabolizers (n≅70 patients) does not suggest that poor and extensive metabolizers have different rates of adverse effects.
No comparison of effectiveness in the two groups has been made. In vitro studies showed that drugs metabolized by other CYP isozymes, including 1A1, 1A2, 2C9, 2C19, and 3A4, are only weak inhibitors of risperidone metabolism. Fluoxetine and Paroxetine Fluoxetine (20 mg once daily) and paroxetine (20 mg once daily), CYP 2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5 to 2.8 fold and 3 to 9 fold respectively.
Fluoxetine did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone by about 10%. When either concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dose of Risperidone for Extended-Release Injectable Suspension. When initiation of fluoxetine or paroxetine is considered, patients may be placed on a lower dose of Risperidone for Extended-Release Injectable Suspension between 2 to 4 weeks before the planned start of fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of risperidone.
When fluoxetine or paroxetine is initiated in patients receiving the recommended dose of 25 mg Risperidone for Extended-Release Injectable Suspension, it is recommended to continue treatment with the 25 mg dose unless clinical judgment necessitates lowering the Risperidone for Extended-Release Injectable Suspension dose to 12.5 mg or necessitates interruption of Risperidone for Extended-Release Injectable Suspension treatment.
When Risperidone for Extended-Release Injectable Suspension is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered. The efficacy of the 12.5 mg dose has not been investigated in clinical trials [see also Dosage and Administration ( 2.5 )] . The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied.
Erythromycin There were no significant interactions between oral risperidone and erythromycin.
7.13Carbamazepine and Other CYP 3A4 Enzyme Inducers
Carbamazepine coadministration with oral risperidone decreased the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone by about 50%. Plasma concentrations of carbamazepine did not appear to be affected. Coadministration of other known CYP 3A4 enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital) with risperidone may cause similar decreases in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone, which could lead to decreased efficacy of Risperidone for Extended-Release Injectable Suspension treatment.
At the initiation of therapy with carbamazepine or other known hepatic enzyme inducers, patients should be closely monitored during the first 4 to 8 weeks, since the dose of Risperidone for Extended-Release Injectable Suspension may need to be adjusted. A dose increase, or additional oral risperidone, may need to be considered. On discontinuation of carbamazepine or other CYP 3A4 hepatic enzyme inducers, the dosage of Risperidone for Extended-Release Injectable Suspension should be re-evaluated and, if necessary, decreased.
Patients may be placed on a lower dose of Risperidone for Extended-Release Injectable Suspension between 2 to 4 weeks before the planned discontinuation of carbamazepine or other CYP 3A4 enzyme inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone. For patients treated with the recommended dose of 25 mg Risperidone for Extended-Release Injectable Suspension and discontinuing from carbamazepine or other CYP 3A4 enzyme inducers, it
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Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including Risperidone for Extended-Release Injectable Suspension, 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/ .
Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations) . Overall, available data from published epidemiologic studies of pregnant women exposed to risperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) .
There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including Risperidone for Extended-Release Injectable Suspension, during pregnancy (see Clinical Considerations) . Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of Risperidone for Extended-Release Injectable Suspension [see Clinical Pharmacology ( 12.3 )] .
The clinical significance of Risperidone for Extended-Release Injectable Suspension administered before pregnancy or anytime during pregnancy is not known. Oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (MRHD) with maternal toxicity observed at 4-times the MRHD based on mg/m 2 body surface area. Risperidone was not teratogenic in rats or rabbits at doses up to 6-times the MRHD based on mg/m 2 body surface area.
Increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the MRHD based on mg/m 2 body surface area. Learning was impaired in offspring of rats when the dams were dosed at 0.6-times the MRHD and offspring mortality increased at doses 0.1 to 3 times the MRHD based on mg/m 2 body surface area. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.
Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including Risperidone for Extended-Release Injectable Suspension, during the third trimester of pregnancy.
These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. There was a small increase in the risk major of birth defects (RR=1.26, 95% CI 1.02 to 1.56) and of cardiac malformations (RR=1.26, 95% CI 0.88 to 1.81) in a subgroup of 1566 women exposed to risperidone during the first trimester of pregnancy; however, there is no mechanism of action to explain the difference in malformation rates.
Animal Data Oral administration of risperidone to pregnant mice during organogenesis caused cleft palate at 10 mg/kg/day which is 3 times the MRHD of 16 mg/day based on mg/m 2 body surface area; maternal toxicity occurred at 4 times the MRHD. Risperidone was not teratogenic when administered orally to rats at 0.6 to 10 mg/kg/day and rabbits at 0.3 to 5 mg/kg/day, which are up to 6 times the MRHD of 16 mg/day risperidone based on mg/m 2 body surface area.
Learning was impaired in offspring of rats dosed orally throughout pregnancy at 1 mg/kg/day which is 0.6 times the MRHD and neuronal cell death increased in fetal brains of offspring of rats dosed during pregnancy at 1 and 2 mg/kg/day which are 0.6 and 1.2 times the MRHD based on mg/m 2 body surface area; postnatal development and growth of the offspring were also delayed. Rat offspring mortality increased during the first 4 days of lactation when pregnant rats were dosed throughout gestation at 0.16 to 5 mg/kg/day which are 0.1 to 3 times the MRHD of 16 mg/day based on mg/m 2 body surface area.
It is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams; a no-effect dose could not be determined. The rate of stillbirths was increased at 2.5 mg/kg or 1.5 times the MRHD based on mg/m 2 body surface area. In a rat cross-fostering study the number of live offspring was decreased, the number of stillbirths increased, and the birth weight was decreased in offspring of drug-treated pregnant rats.
In addition, the number of deaths increased by Day 1 among offspring of drug-treated pregnant rats, regardless of whether or not the offspring were cross-fostered. Risperidone also appeared to impair maternal behavior in that offspring body weight gain and survival (from Day 1 to 4 of lactation) were reduced in offspring born to control but reared by drug-treated dams. All of these effects occurred at 5 mg/kg which is 3 times the MRHD based on mg/m 2 and the only dose tested in the study.
Adverse reactions
The following are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions ( 5.2 )] Neuroleptic malignant syndrome [see Warnings and Precautions ( 5.3 )] Tardive dyskinesia [see Warnings and Precautions ( 5.4 )] Metabolic changes [see Warnings and Precautions ( 5.5 )] Hyperprolactinemia [see Warnings and Precautions ( 5.6 )] Orthostatic hypotension [see Warnings and Precautions (5.7 ) ] Falls [see Warnings and Precautions ( 5.8 )] Leukopenia/Neutropenia and Agranulocytosis [see Warnings and Precautions ( 5.9 )] Potential for cognitive and motor impairment [see Warnings and Precautions ( 5.10) ] Seizures [see Warnings and Precautions (5.11 )] Dysphagia [see Warnings and Precautions ( 5.12 )] Priapism [see Warnings and Precautions ( 5.13 )] Disruption of body temperature regulation [see Warnings and Precautions ( 5.14 )] Avoidance of inadvertent injection into a blood vessel [see Warnings and Precautions ( 5.15 )] Osteodystrophy and tumors in animals [see Warnings and Precautions ( 5.16 ) ] The most common adverse reactions in clinical trials in patients with schizophrenia (≥ 5%) were: headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increased, pain in extremity, and dry mouth.
The most common adverse reactions in the double-blind, placebo-controlled periods of the bipolar disorder trials were weight increased (5% in the monotherapy trial) and tremor and parkinsonism (≥ 10% in the adjunctive treatment trial). The most common adverse reactions that were associated with discontinuation from the 12-week double-blind, placebo-controlled trial in patients with schizophrenia (causing discontinuation in ≥1% of patients) were agitation, depression, anxiety, and akathisia.
Adverse reactions that were associated with discontinuation from the double-blind, placebo-controlled periods of the bipolar disorder trials were hyperglycemia (one patient in the monotherapy trial) and hypokinesia and tardive dyskinesia (one patient each in the adjunctive treatment trial). The data described in this section are derived from a clinical trial database consisting of 2392 patients exposed to one or more doses of Risperidone for Extended-Release Injectable Suspension for the treatment of schizophrenia.
Of these 2392 patients, 332 were patients who received Risperidone for Extended-Release Injectable Suspension while participating in a 12-week double-blind, placebo-controlled trial. Two hundred two (202) of the 332 were schizophrenia patients who received 25 mg or 50 mg Risperidone for Extended-Release Injectable Suspension. The conditions and duration of treatment with Risperidone for Extended-Release Injectable Suspension in the other clinical trials varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 4 years) exposures.
Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs. In addition to the studies in patients with schizophrenia, safety data are presented from a trial assessing the efficacy and safety of Risperidone for Extended-Release Injectable Suspension when administered as monotherapy for maintenance treatment in patients with bipolar I disorder.
The subjects in this multi-center, double-blind, placebo-controlled study were adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who were stable on risperidone (oral or long-acting injection), were stable on other antipsychotics or mood stabilizers, or were experiencing an acute episode. After a 3-week period of treatment with open-label oral risperidone (N=440), subjects who demonstrated an initial response to oral risperidone in this period and those who were stable on risperidone (oral or long-acting injection) at study entry entered into a 26-week stabilization period of open-label Risperidone for Extended-Release Injectable Suspension (N=501).
Subjects who demonstrated a maintained response during this period were then randomized into a 24-month double-blind, placebo-controlled period in which they received Risperidone for Extended-Release Injectable Suspension (N=154) or placebo (N=149) as monotherapy. Subjects who relapsed or who completed the double-blind period could choose to enter an 8-week open-label Risperidone for Extended-Release Injectable Suspension extension period (N=160).
Safety data are also presented from a trial assessing the efficacy and safety of Risperidone for Extended-Release Injectable Suspension when administered as adjunctive maintenance treatment in patients with bipolar disorder. The subjects in this multi-center, double-blind, placebo-controlled study were adult patients who met DSM-IV criteria for Bipolar Disorder Type I or Type II and who experienced at least 4 episodes of mood disorder requiring psychiatric/clinical intervention in the previous 12 months, including at least 2 episodes in the 6 months prior to the start of the study.
At the start of this study, all patients (N=275) entered into a 16-week open-label treatment phase in which they received Risperidone for Extended-Release Injectable Suspension in addition to continuing their treatment as usual, which consisted of various mood stabilizers (primarily lithium and valproate), antidepressants, and/or anxiolytics. Patients who reached remission at the end of this 16-week open-label treatment phase (N=139) were then randomized into a 52-week double-blind, placebo-controlled phase in which they received Risperidone for Extended-Release Injectable Suspension (N=72) or placebo (n=67) as adjunctive treatment in addition to continuing their treatment as usual.
Patients who did not reach remission at the end of the 16-week open-label treatment phase could choose to continue to receive Risperidone for Extended-Release Injectable Suspension as adjunctive therapy in an open-label manner, in addition to continuing their treatment as usual, for up to an additional 36 weeks as clinically indicated for a total period of up to 52 weeks; these patients (N=70) were also included in the evaluation of safety.
Adverse events during exposure to study treatment were obtained by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology. Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of Risperidone for Extended-Release Injectable Suspension (adverse drug reactions) based on the comprehensive assessment of the available adverse event information.
A causal association for Risperidone for Extended-Release Injectable Suspension often cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The majority of all adverse reactions were mild to moderate in severity.
The most common adverse reactions in clinical trials in patients with schizophrenia (≥ 5%) were headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increased, pain in extremity, and dry mouth. The most common adverse reactions in clinical trials in
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Composition
Active ingredients
RISPERIDONE 50MG/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
