Risperdal Information
Risperdal (Risperidone)
Risperdal (Risperidone) Dosage And Administration
For patients who have never taken oral Risperdal (Risperidone) , it is recommended to establish tolerability with oral Risperdal (Risperidone) prior to initiating treatment with Risperdal (Risperidone) CONSTA.
Risperdal (Risperidone) CONSTA should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. Each injection should be administered by a health care professional using the appropriate enclosed safety needle . For deltoid administration, use the 1-inch needle alternating injections between the two arms. For gluteal administration, use the 2-inch needle alternating injections between the two buttocks. Do not administer intravenously.
Risperdal (Risperidone) Dosage Forms And Strengths
Risperdal (Risperidone) CONSTA is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, and 50 mg risperidone. It is provided as a dose pack, consisting of a vial containing the risperidone microspheres, a pre-filled syringe containing 2 mL of diluent for Risperdal (Risperidone) CONSTA, a SmartSite Needle-Free Vial Access Device, and two Needle-Pro safety needles for intramuscular injection (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration).
Risperdal (Risperidone) Contraindications
Risperdal (Risperidone) CONSTA (risperidone) is contraindicated in patients with a known hypersensitivity to the product.
Risperdal (Risperidone) Warnings And Precautions
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperdal (Risperidone) CONSTA(risperidone) is not approved for the treatment of dementia-related psychosis (see ).
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of 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.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases in which the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: (1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
A syndrome 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 rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to 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 are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, Risperdal (Risperidone) CONSTA 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 who suffer from a chronic illness that: (1) 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 smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient treated with Risperdal (Risperidone) CONSTA, drug discontinuation should be considered. However, some patients may require treatment with Risperdal (Risperidone) CONSTA despite the presence of the syndrome.
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.
As with other drugs that antagonize dopamine D 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.
Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.
Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent , a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer. An increase in pituitary gland, mammary gland, and pancreatic islet cell neoplasia (mammary adenocarcinomas, pituitary and pancreatic adenomas) was observed in the risperidone carcinogenicity studies conducted in mice and rats . Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans; the available evidence is considered too limited to be conclusive at this time.
Risperdal (Risperidone) CONSTA may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period with oral risperidone, probably reflecting its alpha-adrenergic antagonistic properties. Syncope was reported in 0.8% (12/1499 patients) of patients treated with Risperdal (Risperidone) CONSTA in multiple-dose studies. Patients should be instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position).
Risperdal (Risperidone) CONSTA should be used with particular caution in (1) patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension, e.g., dehydration and hypovolemia, and (2) 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 Risperdal (Risperidone) and antihypertensive medication.
Clinical experience with Risperdal (Risperidone) CONSTA in patients with certain concomitant systemic illnesses is limited. Patients with Parkinson's Disease or Dementia with Lewy Bodies who receive antipsychotics, including Risperdal (Risperidone) CONSTA, are reported to have an increased sensitivity to antipsychotic medications. Manifestations of this increased sensitivity have been reported to include confusion, obtundation, postural instability with frequent falls, extrapyramidal symptoms, and clinical features consistent with the neuroleptic malignant syndrome.
Caution is advisable when using Risperdal (Risperidone) CONSTA in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Risperdal (Risperidone) CONSTA has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from clinical studies during the product's premarket testing.
Increased plasma concentrations of risperidone and 9-hydroxyrisperidone occur in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m) treated with oral Risperdal (Risperidone) ; an increase in the free fraction of risperidone is also seen in patients with severe hepatic impairment. Patients with renal or hepatic impairment should be carefully titrated on oral Risperdal (Risperidone) before treatment with Risperdal (Risperidone) CONSTA is initiated at a dose of 25 mg. A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with renal or hepatic impairment .
Risperdal (Risperidone) CONSTA produced osteodystrophy in male and female rats in a 1-year toxicity study and a 2-year carcinogenicity study at a dose of 40 mg/kg administered IM every 2 weeks.
Risperdal (Risperidone) CONSTA produced renal tubular tumors (adenoma, adenocarcinoma) and adrenomedullary pheochromocytomas in male rats in the 2-year carcinogenicity study at 40 mg/kg administered IM every 2 weeks. In addition, Risperdal (Risperidone) CONSTA produced an increase in a marker of cellular proliferation in renal tissue in males in the 1-year toxicity study and in renal tumor-bearing males in the 2-year carcinogenicity study at 40 mg/kg administered IM every 2 weeks. (Cellular proliferation was not measured at the low dose or in females in either study.)
The effect dose for osteodystrophy and the tumor findings is 8 times the IM maximum recommended human dose (MRHD) (50 mg) on a mg/m basis and is associated with a plasma exposure (AUC) 2 times the expected plasma exposure (AUC) at the IM MRHD. The no-effect dose for these findings was 5 mg/kg (equal to the IM MRHD on a mg/m basis). Plasma exposure (AUC) at the no-effect dose was one third the expected plasma exposure (AUC) at the IM MRHD.
Neither the renal or adrenal tumors, nor osteodystrophy, were seen in studies of orally administered risperidone.
The renal tubular and adrenomedullary tumors in male rats and other tumor findings are described in more detail in Section 13.1 (Carcinogenicity, Mutagenesis, Impairment of Fertility).
The relevance of these findings to human risk is unknown.
Risperdal (Risperidone) Adverse Reactions
The following are discussed in more detail in other sections of the labeling:
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 Risperdal (Risperidone) CONSTA for the treatment of schizophrenia. Of these 2392 patients, 332 were patients who received Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA. The conditions and duration of treatment with Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA (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 Risperdal (Risperidone) CONSTA (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 Risperdal (Risperidone) CONSTA extension period (n=160).
Safety data are also presented from a trial assessing the efficacy and safety of Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA (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 Risperdal (Risperidone) CONSTA 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 Risperdal (Risperidone) CONSTA (adverse drug reactions) based on the comprehensive assessment of the available adverse event information. A causal association for Risperdal (Risperidone) CONSTA 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.
Risperdal (Risperidone) Drug Interactions
The interactions of Risperdal (Risperidone) CONSTA with coadministration of other drugs have not been systematically evaluated. The drug interaction data provided in this section is based on studies with oral Risperdal (Risperidone) .
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 . 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.
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Risperdal (Risperidone) Use In Specific Populations
Risperdal (Risperidone) CONSTA has not been studied in children younger than 18 years old. However, juvenile animal toxicology studies have been conducted with oral risperidone.
Juvenile dogs were treated for 40 weeks with oral risperidone doses of 0.31, 1.25, or 5 mg/kg/day. Decreased bone length and density were seen, with a no-effect dose of 0.31 mg/kg/day. This dose produced plasma levels (AUC) of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) which were similar to those in children and adolescents receiving the maximum recommended human dose (MRHD) of 6 mg/day. In addition, a delay in sexual maturation was seen at all doses in both males and females. The above effects showed little or no reversibility in females after a 12 week drug-free recovery period.
In a study in which juvenile rats were treated with oral risperidone from days 12 to 50 of age, a reversible impairment of performance in a test of learning and memory was seen, in females only, with a no-effect dose of 0.63 mg/kg/day. This dose produced plasma levels (AUC) of risperidone plus paliperidone about half those observed in humans at the MRHD. No other consistent effects on neurobehavioral or reproductive development were seen up to the highest testable dose (1.25 mg/kg/day). This dose produced plasma levels (AUC) of risperidone plus paliperidone which were about two thirds of those observed in humans at the MRHD.
The long-term effects of risperidone on growth and sexual maturation have not been fully evaluated in children and adolescents.
Risperdal (Risperidone) Overdosage
No cases of overdose were reported in premarketing studies with Risperdal (Risperidone) CONSTA. Because Risperdal (Risperidone) CONSTA is to be administered by health care professionals, the potential for overdosage by patients is low.
In premarketing experience with oral Risperdal (Risperidone) , there were eight reports of acute Risperdal (Risperidone) overdosage, with estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. One case, involving an estimated overdose of 240 mg, was associated with hyponatremia, hypokalemia, prolonged QT, and widened QRS. Another case, involving an estimated overdose of 36 mg, was associated with a seizure.
Postmarketing experience with oral Risperdal (Risperidone) includes reports of acute overdose, with estimated doses of up to 360 mg. In general, the most frequently reported signs and symptoms are those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Other adverse reactions reported since market introduction related to oral Risperdal (Risperidone) overdose include prolonged QT interval and convulsions. Torsade de pointes has been reported in association with combined overdose of oral Risperdal (Risperidone) and paroxetine.
In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of QT prolonging effects that might be additive to those of risperidone. Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of risperidone, resulting in problematic hypotension.
There is no specific antidote to risperidone. Therefore, appropriate supportive measures should be instituted. The possibility of multiple drug involvement should be considered. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of risperidone-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.
Risperdal (Risperidone) Description
Risperidone is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives. The chemical designation is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. Its molecular formula is CHFNO and its molecular weight is 410.49. The structural formula is:
Risperidone is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and 0.1 HCl.
Risperdal (Risperidone) CONSTA (risperidone) Long-Acting Injection is a combination of extended-release microspheres for injection and diluent for parenteral use.
The extended-release microspheres formulation is a white to off-white, free-flowing powder that is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, or 50 mg risperidone per vial. Risperidone is micro-encapsulated in 7525 polylactide-co-glycolide (PLG) at a concentration of 381 mg risperidone per gram of microspheres.
The diluent for parenteral use is a clear, colorless solution. Composition of the diluent includes polysorbate 20, sodium carboxymethyl cellulose, disodium hydrogen phosphate dihydrate, citric acid anhydrous, sodium chloride, sodium hydroxide, and water for injection. The microspheres are suspended in the diluent prior to injection.
Risperdal (Risperidone) CONSTA is provided as a dose pack, consisting of a vial containing the microspheres, a pre-filled syringe containing the diluent, a SmartSite Needle-Free Vial Access Device, and two Needle-Pro safety needles (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration).
Risperdal (Risperidone) Clinical Pharmacology
The mechanism of action of Risperdal (Risperidone) CONSTA, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D) and serotonin Type 2 (5HT) receptor antagonism.
Risperdal (Risperidone) is a selective monoaminergic antagonist with high affinity (Ki of 0.12 to 7.3 nM) for the serotonin Type 2 (5HT), dopamine Type 2 (D), α1 and α2 adrenergic, and H histaminergic receptors. Risperdal (Risperidone) acts as an antagonist at other receptors, but with lower potency. Risperdal (Risperidone) has low to moderate affinity (Ki of 47 to 253 nM) for the serotonin 5HT, 5HT, and 5HT receptors, weak affinity (Ki of 620 to 800 nM) for the dopamine D and haloperidol-sensitive sigma site, and no affinity (when tested at concentrations >10 M) for cholinergic muscarinic or β1 and β2 adrenergic receptors.
Risperdal (Risperidone) Clinical Studies
The effectiveness of Risperdal (Risperidone) CONSTA in the treatment of schizophrenia was established, in part, on the basis of extrapolation from the established effectiveness of the oral formulation of risperidone. In addition, the effectiveness of Risperdal (Risperidone) CONSTA in the treatment of schizophrenia was established in a 12-week, placebo-controlled trial in adult psychotic inpatients and outpatients who met the DSM-IV criteria for schizophrenia.
Efficacy data were obtained from 400 patients with schizophrenia who were randomized to receive injections of 25 mg, 50 mg, or 75 mg Risperdal (Risperidone) CONSTA or placebo every 2 weeks. During a 1-week run-in period, patients were discontinued from other antipsychotics and were titrated to a dose of 4 mg oral Risperdal (Risperidone) . Patients who received Risperdal (Risperidone) CONSTA were given doses of oral Risperdal (Risperidone) (2 mg for patients in the 25-mg group, 4 mg for patients in the 50-mg group, and 6 mg for patients in the 75-mg group) for the 3 weeks after the first injection to provide therapeutic plasma concentrations until the main release phase of risperidone from the injection site had begun. Patients who received placebo injections were given placebo tablets.
Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS), a validated, multi-item inventory, composed of five subscales to evaluate positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression.
The primary efficacy variable in this trial was change from baseline to endpoint in the total PANSS score. The mean total PANSS score at baseline for schizophrenic patients in this study was 81.5.
Total PANSS scores showed significant improvement in the change from baseline to endpoint in schizophrenic patients treated with each dose of Risperdal (Risperidone) CONSTA (25 mg, 50 mg, or 75 mg) compared with patients treated with placebo. While there were no statistically significant differences between the treatment effects for the three dose groups, the effect size for the 75 mg dose group was actually numerically less than that observed for the 50 mg dose group.
Subgroup analyses did not indicate any differences in treatment outcome as a function of age, race, or gender.
The effectiveness of Risperdal (Risperidone) CONSTA for the maintenance treatment of Bipolar I Disorder was established in a multicenter, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I, who were stable on medications or experiencing an acute manic or mixed episode.
A total of 501 patients were treated during a 26-week open-label period with Risperdal (Risperidone) CONSTA (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg; in patients not tolerating the 25 mg dose, the dose could be reduced to 12.5 mg). In the open-label phase, 303 (60%) patients were judged to be stable and were randomized to double-blind treatment with either the same dose of Risperdal (Risperidone) CONSTA or placebo and monitored for relapse. The primary endpoint was time to relapse to any mood episode (depression, mania, hypomania, or mixed).
Time to relapse was delayed in patients receiving Risperdal (Risperidone) CONSTAmonotherapy as compared to placebo. The majority of relapses were due to manic rather than depressive symptoms. Based on their bipolar disorder history, subjects entering this study had had, on average, more manic episodes than depressive episodes.
The effectiveness of Risperdal (Risperidone) CONSTA as an adjunct to treatment with lithium or valproate for the maintenance treatment of Bipolar Disorder was established in a multi-center, randomized, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I 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.
A total of 240 patients were treated during a 16-week open-label period with Risperdal (Risperidone) CONSTA (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg), as adjunctive therapy in addition to continuing their treatment as usual for their bipolar disorder, which consisted of mood stabilizers (primarily lithium and valproate), antidepressants, and/or anxiolytics. All oral antipsychotics were discontinued after the first three weeks of the initial Risperdal (Risperidone) CONSTA injection. In the open-label phase, 124 (51.7%) were judged to be stable for at least the last 4 weeks and were randomized to double-blind treatment with either the same dose of Risperdal (Risperidone) CONSTA or placebo in addition to continuing their treatment as usual and monitored for relapse during a 52-week period. The primary endpoint was time to relapse to any new mood episode (depression, mania, hypomania, or mixed).
Time to relapse was delayed in patients receiving adjunctive therapy with Risperdal (Risperidone) CONSTAas compared to placebo. The relapse types were about half depressive and half manic or mixed episodes.
Risperdal (Risperidone) How Supplied/storage And Handling
Risperdal (Risperidone) CONSTA (risperidone) is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, or 50 mg risperidone. It is provided as a dose pack, consisting of a vial containing the risperidone microspheres, a pre-filled syringe containing 2 mL of diluent for Risperdal (Risperidone) CONSTA, a SmartSite Needle-Free Vial Access Device, and two Needle-Pro safety needles for intramuscular injection (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration).
12.5-mg vial/kit (NDC 50458-309-11): 41 mg (equivalent to 12.5 mg of risperidone) of a white to off-white powder provided in a vial with a violet flip-off cap (NDC 50458-309-01).
25-mg vial/kit (NDC 50458-306-11): 78 mg (equivalent to 25 mg of risperidone) of a white to off-white powder provided in a vial with a pink flip-off cap (NDC 50458-306-01).
37.5-mg vial/kit (NDC 50458-307-11): 116 mg (equivalent to 37.5 mg of risperidone) of a white to off-white powder provided in a vial with a green flip-off cap (NDC 50458-307-01).
50-mg vial/kit (NDC 50458-308-11): 152 mg (equivalent to 50 mg of risperidone) of a white to off-white powder provided in a vial with a blue flip-off cap (NDC 50458-308-01).
Risperdal (Risperidone) Patient Counseling Information
Physicians are advised to discuss the following issues with patients for whom they prescribe Risperdal (Risperidone) CONSTA.
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