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Medically reviewed by Kovalenko Svetlana Olegovna, PharmD. Last updated on 03.04.2022
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Dosage Forms And Strengths
RISPERDAL® Tablets are available in the following strengths and colors: 0.25 mg (dark yellow), 0.5 mg (red-brown), 1 mg (white), 2 mg (orange), 3 mg (yellow), and 4 mg (green). All are capsule shaped, and imprinted with “JANSSEN” on one side and either “Ris 0.25”, “Ris 0.5”, “R1”, “R2”, “R3”, or “R4” on the other side according to their respective strengths.
RISPERDAL® Oral Solution is available in a 1 mg/mL strength.
RISPERDAL® M-TAB® Orally Disintegrating Tablets are available in the following strengths, colors, and shapes: 0.5 mg (light coral, round), 1 mg (light coral, square), 2 mg (coral, square), 3 mg (coral, round), and 4 mg (coral, round). All are biconvex and etched on one side with “R0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths.
RISPERDAL® (risperidone) Tablets
RISPERDAL® (risperidone) Tablets are imprinted “JANSSEN” on one side and either “Ris 0.25”, “Ris 0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths.
0.25 mg dark yellow, capsule-shaped tablets: bottles of 60 NDC 50458-301-04, bottles of 500 NDC 50458-301-50, and hospital unit dose blister packs of 100 NDC 50458-301-01.
0.5 mg red-brown, capsule-shaped tablets: bottles of 60 NDC 50458-302-06, bottles of 500 NDC 50458-302-50, and hospital unit dose blister packs of 100 NDC 50458-302-01.
1 mg white, capsule-shaped tablets: bottles of 60 NDC 50458-300-06, bottles of 500 NDC 50458-300-50, and hospital unit dose blister packs of 100 NDC 50458-300-01.
2 mg orange, capsule-shaped tablets: bottles of 60 NDC 50458-320-06, bottles of 500 NDC 50458-320-50, and hospital unit dose blister packs of 100 NDC 50458-320-01.
3 mg yellow, capsule-shaped tablets: bottles of 60 NDC 50458-330-06, bottles of 500 NDC 50458-330-50, and hospital unit dose blister packs of 100 NDC 50458-330-01.
4 mg green, capsule-shaped tablets: bottles of 60 NDC 50458-350-06 and hospital unit dose blister packs of 100 NDC 50458-350-01.
RISPERDAL® (risperidone) Oral Solution
RISPERDAL® (risperidone) 1 mg/mL Oral Solution (NDC 50458-305-03) is supplied in 30 mL bottles with a calibrated (in milligrams and milliliters) pipette. The minimum calibrated volume is 0.25 mL, while the maximum calibrated volume is 3 mL.
RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets
RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets are etched on one side with “R0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths. RISPERDAL® MTAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are packaged in blister packs of 4 (2 X 2) tablets. Orally Disintegrating Tablets 3 mg and 4 mg are packaged in a child-resistant pouch containing a blister with 1 tablet.
0.5 mg light coral, round, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-395-28, and long-term care blister packaging of 30 tablets NDC 50458-395-30.
1 mg light coral, square, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-315-28, and long-term care blister packaging of 30 tablets NDC 50458-315-30.
2 mg coral, square, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-325-28.
3 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-335-28.
4 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-355-28.
Storage And Handling
RISPERDAL® Tablets should be stored at controlled room temperature 15°-25°C (59°-77°F). Protect from light and moisture.
RISPERDAL® 1 mg/mL Oral Solution should be stored at controlled room temperature 15°25°C (59°-77°F). Protect from light and freezing.
RISPERDAL® M-TAB® Orally Disintegrating Tablets should be stored at controlled room temperature 15°-25°C (59°-77°F).
Keep out of reach of children.
RISPERDAL® Tablets Active ingredient is made in Ireland Finished product is manufactured by: Janssen Ortho, LLC Gurabo, Puerto Rico 00778. RISPERDAL® Oral Solution Finished product is manufactured by: Janssen Pharmaceutica NV Beerse, Belgium. RISPERDAL® M-TAB® Orally Disintegrating Tablets Active ingredient is made in Ireland Finished product is manufactured by: Janssen Ortho, LLC Gurabo, Puerto Rico 00778. RISPERDAL® Tablets, RISPERDAL® M-TAB® Orally Disintegrating Tablets, and RISPERDAL® Oral Solution are manufactured for: Janssen Pharmaceuticals, Inc. Titusville, NJ 08560. Revised: Mar 2016
Schizophrenia
RISPERDAL® (risperidone) is indicated for the treatment of schizophrenia. Efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults.
Bipolar Mania
Monotherapy
RISPERDAL® is indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder. Efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years).
Adjunctive Therapy
RISPERDAL® adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder. Efficacy was established in one short-term trial in adults.
Irritability Associated With Autistic Disorder
RISPERDAL® is indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. Efficacy was established in 3 short-term trials in children and adolescents (ages 5 to 17 years).
Table 1: Recommended Daily Dosage by Indication
Initial Dose | Titration (Increments) | Target Dose | Effective Dose Range | |
Schizophrenia: adults | 2 mg | 1 to 2 mg | 4 to 8 mg | 4 to 16 mg |
Schizophrenia: adolescents | 0.5 mg | 0.5 to 1 mg | 3 mg | 1 to 6 mg |
Bipolar mania: adults | 2 to 3 mg | 1 mg | 1 to 6 mg | 1 to 6 mg |
Bipolar mania: children and adolescents | 0.5 mg | 0.5 to 1 mg | 1 to 2.5 mg | 1 to 6 mg |
Irritability in autistic disorder | 0.25 mg Can increase to 0.5 mg by Day 4: (body weight less than 20 kg) 0.5 mg Can increase to 1 mg by Day 4: (body weight greater than or equal to 20 kg) |
After Day 4, at intervals of > 2 weeks: 0.25 mg (body weight less than 20 kg) 0.5 mg (body weight greater than or equal to 20 kg) |
0.5 mg: (body weight less than 20 kg) 1 mg: (body weight greater than or equal to 20 kg) |
0.5 to 3 mg |
Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily. May increase to dosages above 1.5 mg twice daily at intervals of one week or longer.
Schizophrenia
Adults
Usual Initial Dose
RISPERDAL® can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in clinical trials.
Adolescents
The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional benefit was observed above 3 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
Maintenance Therapy
While it is unknown how long a patient with schizophrenia should remain on RISPERDAL®, the effectiveness of RISPERDAL® 2 mg per day to 8 mg per day at delaying relapse was demonstrated in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years. Both adult and adolescent patients who respond acutely should generally be maintained on their effective dose beyond the acute episode. Patients should be periodically reassessed to determine the need for maintenance treatment.
Reinitiation Of Treatment In Patients Previously Discontinued
Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off RISPERDAL®, the initial titration schedule should be followed.
Switching From Other Antipsychotics
There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to RISPERDAL®, or treating patients with concomitant antipsychotics.
Bipolar Mania
Usual Dose
Adults
The initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 mg to 6 mg per day. RISPERDAL® doses higher than 6 mg per day were not studied.
Pediatrics
The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to the recommended target dose of 1 mg to 2.5 mg per day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
Maintenance Therapy
There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with RISPERDAL®. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of RISPERDAL® in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
Irritability Associated With Autistic Disorder – Pediatrics (Children and Adolescents)
The dosage of RISPERDAL® should be individualized according to the response and tolerability of the patient. The total daily dose of RISPERDAL® can be administered once daily, or half the total daily dose can be administered twice daily.
For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days, the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and 1.0 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days. In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No dosing data are available for children who weigh less than 15 kg.
Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of efficacy and safety. The physician who elects to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.
Dosing In Patients With Severe Renal Or Hepatic Impairment
For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10-15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater.
Dose Adjustments For Specific Drug Interactions
When RISPERDAL® is co-administered with enzyme inducers (e.g., carbamazepine), the dose of RISPERDAL® should be increased up to double the patient's usual dose. It may be necessary to decrease the RISPERDAL® dose when enzyme inducers such as carbamazepine are discontinued. Similar effect may be expected with coadministration of RISPERDAL® with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).
When fluoxetine or paroxetine is co-administered with RISPERDAL® , the dose of RISPERDAL® should be reduced. The RISPERDAL® dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, RISPERDAL® should be titrated slowly. It may be necessary to increase the RISPERDAL® dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued.
Administration Of RISPERDAL® Oral Solution
RISPERDAL® Oral Solution can be administered directly from the calibrated pipette, or can be mixed with a beverage prior to administration. RISPERDAL® Oral Solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea.
Directions For Use Of RISPERDAL® M-TAB® Orally Disintegrating Tablets
Tablet Accessing
RISPERDAL®M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg
RISPERDAL® M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are supplied in blister packs of 4 tablets each.
Do not open the blister until ready to administer. For single tablet removal, separate one of the four blister units by tearing apart at the perforations. Bend the corner where indicated. Peel back foil to expose the tablet. DO NOT push the tablet through the foil because this could damage the tablet.
RISPERDAL®M-TAB®Orally Disintegrating Tablets 3 mg and 4 mg
RISPERDAL® M-TAB® Orally Disintegrating Tablets 3 mg and 4 mg are supplied in a child-resistant pouch containing a blister with 1 tablet each.
The child-resistant pouch should be torn open at the notch to access the blister. Do not open the blister until ready to administer. Peel back foil from the side to expose the tablet. DO NOT push the tablet through the foil, because this could damage the tablet.
Tablet Administration
Using dry hands, remove the tablet from the blister unit and immediately place the entire RISPERDAL® M-TAB® Orally Disintegrating Tablet on the tongue. The RISPERDAL® MTAB® Orally Disintegrating Tablet should be consumed immediately, as the tablet cannot be stored once removed from the blister unit. RISPERDAL® M-TAB® Orally Disintegrating Tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.
RISPERDAL® is contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the RISPERDAL® 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.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
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. 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.
In two of four placebo-controlled trials in elderly patients with dementia-related psychosis, a higher incidence of mortality was observed in patients treated with furosemide plus RISPERDAL® when compared to patients treated with RISPERDAL® alone or with placebo plus furosemide. No pathological mechanism has been identified to explain this finding, and no consistent pattern for cause of death was observed.
RISPERDAL® (risperidone) is not approved for the treatment of dementia-related psychosis.
Cerebrovascular Adverse Reactions, Including Stroke, In Elderly Patients With Dementia-Related Psychosis
Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73-97) in trials of 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 risperidone compared to patients treated with placebo. RISPERDAL® is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome
Antipsychotic drugs including RISPERDAL® can cause a potentially fatal symptom complex referred to as Neuroleptic Malignant Syndrome (NMS). Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase (CPK), 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.
Tardive Dyskinesia
A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. 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, prescribe RISPERDAL® 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®, consider drug discontinuation. However, some patients may require treatment with RISPERDAL® despite the presence of the syndrome.
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
Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, have been reported in patients treated with atypical antipsychotics including RISPERDAL®. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics, including RISPERDAL®, should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including RISPERDAL®, should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics, including RISPERDAL®, 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 RISPERDAL®, should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including RISPERDAL®, was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of RISPERDAL®.
Pooled data from three double-blind, placebo-controlled schizophrenia studies and four double-blind, placebo-controlled bipolar monotherapy studies are presented in Table 2.
Table 2: Change in Random Glucose from Seven
Placebo-Controlled, 3-to 8-Week, Fixed- or Flexible-Dose Studies in Adult
Subjects with Schizophrenia or Bipolar Mania
Placebo n=555 |
RISPERDAL® | ||
1-8 mg/day Mean change from baseline (mg/dL) n=748 |
> 8-16 mg/day n=164 |
||
Serum Glucose | -1.4 | 0.8 Proportion of patients with shifts | 0.6 |
Serum Glucose ( < 140 mg/dL to ≥ 200 mg/dL) | 0.6% (3/525) | 0.4% (3/702) | 0% (0/158) |
In longer-term, controlled and uncontrolled studies, RISPERDAL® was associated with a mean change in glucose of +2.8 mg/dL at Week 24 (n=151) and +4.1 mg/dL at Week 48 (n=50).
Data from the placebo-controlled 3- to 6-week study in children and adolescents with schizophrenia (13-17 years of age), bipolar mania (10-17 years of age), or autistic disorder (5 to 17 years of age) are presented in Table 3.
Table 3: Change in Fasting
Glucose from Three Placebo-Controlled, 3- to 6-Week, Fixed-Dose Studies in
Children and Adolescents with Schizophrenia (13-17 years of age), Bipolar Mania
(10-17 years of age), or Autistic Disorder (5 to 17 years of age)
Placebo | RISPERDAL® 0.5-6 mg/day | |
Mean change from baseline (mg/dL) | ||
n=76 | n=135 | |
Serum Glucose | -1.3 | 2.6 |
Proportion of patients with shifts | ||
Serum Glucose ( < 100 mg/dL to ≥ 126 mg/dL) | 0% (0/64) | 0.8% (1/120) |
In longer-term, uncontrolled, open-label extension pediatric studies, RISPERDAL® was associated with a mean change in fasting glucose of +5.2 mg/dL at Week 24 (n=119).
Dyslipidemia
Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
Pooled data from 7 placebo-controlled, 3- to 8- week, fixed- or flexible-dose studies in adult subjects with schizophrenia or bipolar mania are presented in Table 4.
Table 4: Change in Random Lipids from Seven
Placebo-Controlled, 3-to 8-Week, Fixed- or Flexible-Dose Studies in Adult
Subjects with Schizophrenia or Bipolar Mania
Placebo | RISPERDAL® | ||
1-8 mg/day | > 8-16 mg/day | ||
Mean change from baseline (mg/dL) | |||
Cholesterol | n=559 | n=742 | n=156 |
Change from baseline | 0.6 | 6.9 | 1.8 |
Triglycerides | n=183 | n=307 | n=123 |
Change from baseline | -17.4 | -4.9 | -8.3 |
Cholesterol ( < 200 mg/dL to ≥ 240 mg/dL) | Proportion of patients With Shifts | ||
2.7% | 4.3% | 6.3% | |
(10/368) | (22/516) | (6/96) | |
Triglycerides ( < 500 mg/dL to ≥ 500 mg/dL) | 1.1% | 2.7% | 2.5% |
(2/180) | (8/301) | (3/121) |
In longer-term, controlled and uncontrolled studies, RISPERDAL® was associated with a mean change in (a) non-fasting cholesterol of +4.4 mg/dL at Week 24 (n=231) and +5.5 mg/dL at Week 48 (n=86); and (b) non-fasting triglycerides of +19.9 mg/dL at Week 24 (n=52).
Pooled data from 3 placebo-controlled, 3- to 6-week, fixed-dose studies in children and adolescents with schizophrenia (13-17 years of age), bipolar mania (10-17 years of age), or autistic disorder (5-17 years of age) are presented in Table 5.
Table 5: Change in Fasting Lipids from Three
Placebo-Controlled, 3-to 6-Week, Fixed-Dose Studies in Children and Adolescents
with Schizophrenia (13-17 Years of Age), Bipolar Mania (10-17 Years of Age), or
Autistic Disorder (5 to 17 Years of Age)
Placebo | RISPERDAL® 0.5-6 mg/day | |
Mean change from baseline (mg/dL) | ||
Cholesterol | n=74 | n=133 |
Change from baseline | 0.3 | -0.3 |
LDL | n=22 | n=22 |
Change from baseline | 3.7 | 0.5 |
HDL | n=22 | n=22 |
Change from baseline | 1.6 | -1.9 |
Triglycerides | n=77 | n=138 |
Change from baseline | -9.0 | -2.6 |
Proportion of patients with shifts | ||
Cholesterol ( < 170 mg/dL to ≥ 200 mg/dL) | 2.4% (1/42) | 3.8% (3/80) |
LDL ( < 110 mg/dL to ≥ 130 mg/dL) | 0% (0/16) | 0% (0/16) |
HDL ( ≥ 40 mg/dL to < 40 mg/dL) | 0% (0/19) | 10% (2/20) |
Triglycerides ( < 150 mg/dL to ≥ 200 mg/dL) | 1.5% (1/65) | 7.1% (8/113) |
In longer-term, uncontrolled, open-label extension pediatric studies, RISPERDAL® was associated with a mean change in (a) fasting cholesterol of +2.1 mg/dL at Week 24 (n=114); (b) fasting LDL of -0.2 mg/dL at Week 24 (n=103); (c) fasting HDL of +0.4 mg/dL at Week 24 (n=103); and (d) fasting triglycerides of +6.8 mg/dL at Week 24 (n=120).
Weight Gain
Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Data on mean changes in body weight and the proportion of subjects meeting a weight gain criterion of 7% or greater of body weight from 7 placebo-controlled, 3- to 8- week, fixed- or flexible-dose studies in adult subjects with schizophrenia or bipolar mania are presented in Table 6.
Table 6: Mean Change in Body Weight (kg) and the
Proportion of Subjects with ≥ 7% Gain in Body Weight From Seven
Placebo-Controlled, 3- to 8-Week, Fixed- or Flexible-Dose Studies in Adult
Subjects With Schizophrenia or Bipolar Mania
Placebo (n=597) |
RISPERDAL® | ||
1-8 mg/day (n=769) |
> 8-16 mg/day (n=158) |
||
Weight (kg) | |||
Change from baseline | -0.3 | 0.7 | 2.2 |
Weight Gain | |||
≥ 7% increase from baseline | 2.9% | 8.7% | 20.9% |
In longer-term, controlled and uncontrolled studies, RISPERDAL® was associated with a mean change in weight of +4.3 kg at Week 24 (n=395) and +5.3 kg at Week 48 (n=203).
Data on mean changes in body weight and the proportion of subjects meeting the criterion of ≥ 7% gain in body weight from nine placebo-controlled, 3- to 8-week, fixed-dose studies in children and adolescents with schizophrenia (13-17 years of age), bipolar mania (10-17 years of age), autistic disorder (5-17 years of age), or other psychiatric disorders (5-17 years of age) are presented in Table 7.
Table 7: Mean Change in Body
Weight (kg) and the Proportion of Subjects With ≥ 7% Gain in Body Weight
From Nine Placebo-Controlled, 3- to 8-Week, Fixed-Dose Studies in Children and
Adolescents With Schizophrenia (13-17 Years of Age), Bipolar Mania (10-17 Years
of Age), Autistic Disorder (5 to 17 Years of Age) or Other Psychiatric
Disorders (5-17 Years of Age)
Placebo (n=375) | RISPERDAL® 0.5-6 mg/day (n=448) | |
Weight (kg) | ||
Change from baseline | 0.6 | 2.0 |
Weight Gain | ||
≥ 7% increase from baseline | 6.9% | 32.6% |
In longer-term, uncontrolled, open-label extension pediatric studies, RISPERDAL® was associated with a mean change in weight of +5.5 kg at Week 24 (n=748) and +8.0 kg at Week 48 (n=242).
In a long-term, open-label extension study in adolescent patients with schizophrenia, weight increase was reported as a treatment-emergent adverse event in 14% of patients. In 103 adolescent patients with schizophrenia, a mean increase of 9.0 kg was observed after 8 months of RISPERDAL® treatment. The majority of that increase was observed within the first 6 months. The average percentiles at baseline and 8 months, respectively, were 56 and 72 for weight, 55 and 58 for height, and 51 and 71 for body mass index.
In long-term, open-label trials (studies in patients with autistic disorder or other psychiatric disorders), a mean increase of 7.5 kg after 12 months of RISPERDAL® treatment was observed, which was higher than the expected normal weight gain (approximately 3 to 3.5 kg per year adjusted for age, based on Centers for Disease Control and Prevention normative data). The majority of that increase occurred within the first 6 months of exposure to RISPERDAL®. The average percentiles at baseline and 12 months, respectively, were 49 and 60 for weight, 48 and 53 for height, and 50 and 62 for body mass index.
In one 3-week, placebo-controlled trial in children and adolescent patients with acute manic or mixed episodes of bipolar I disorder, increases in body weight were higher in the RISPERDAL® groups than the placebo group, but not dose related (1.90 kg in the RISPERDAL® 0.5-2.5 mg group, 1.44 kg in the RISPERDAL® 3-6 mg group, and 0.65 kg in the placebo group). A similar trend was observed in the mean change from baseline in body mass index.
When treating pediatric patients with RISPERDAL® for any indication, weight gain should be assessed against that expected with normal growth.
Hyperprolactinemia
As with other drugs that antagonize dopamine D2 receptors, RISPERDAL® elevates prolactin levels and the elevation persists during chronic administration. RISPERDAL® 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 in vitro, 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.
Orthostatic Hypotension
RISPERDAL® may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflecting its alpha-adrenergic antagonistic properties. Syncope was reported in 0.2% (6/2607) of RISPERDAL®-treated patients in Phase 2 and 3 studies in adults with schizophrenia. The risk of orthostatic hypotension and syncope may be minimized by limiting the initial dose to 2 mg total (either once daily or 1 mg twice daily) in normal adults and 0.5 mg twice daily in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered in patients for whom this is of concern. A dose reduction should be considered if hypotension occurs. RISPERDAL® should be used with particular caution in 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. Clinically significant hypotension has been observed with concomitant use of RISPERDAL® and antihypertensive medication.
Leukopenia, Neutropenia, And Agranulocytosis
Class Effect
In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including RISPERDAL®. Agranulocytosis has also been reported.
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of RISPERDAL® should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm³) should discontinue RISPERDAL® and have their WBC followed until recovery.
Potential For Cognitive And Motor Impairment
Somnolence was a commonly reported adverse reaction associated with RISPERDAL® treatment, especially when ascertained by direct questioning of patients. This adverse reaction is dose-related, and in a study utilizing a checklist to detect adverse events, 41% of the high-dose patients (RISPERDAL® 16 mg/day) reported somnolence compared to 16% of placebo patients.
Direct questioning is more sensitive for detecting adverse events than spontaneous reporting, by which 8% of RISPERDAL® 16 mg/day patients and 1% of placebo patients reported somnolence as an adverse reaction. Since RISPERDAL® has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that RISPERDAL® therapy does not affect them adversely.
Seizures
During premarketing testing in adult patients with schizophrenia, seizures occurred in 0.3% (9/2607) of RISPERDAL®-treated patients, two in association with hyponatremia. RISPERDAL® should be used cautiously in patients with a history of seizures.
Dysphagia
Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's dementia. RISPERDAL® and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
Priapism
Priapism has been reported during postmarketing surveillance. Severe priapism may require surgical intervention.
Body Temperature Regulation
Disruption of body temperature regulation has been attributed to antipsychotic agents. Both hyperthermia and hypothermia have been reported in association with oral RISPERDAL® use. Caution is advised when prescribing for patients who will be exposed to temperature extremes.
Patients With Phenylketonuria
Inform patients that RISPERDAL® M-TAB® Orally Disintegrating Tablets contain phenylalanine. Phenylalanine is a component of aspartame. Each 4 mg RISPERDAL® M-TAB® Orally Disintegrating Tablet contains 0.84 mg phenylalanine; each 3 mg RISPERDAL® MTAB® Orally Disintegrating Tablet contains 0.63 mg phenylalanine; each 2 mg RISPERDAL® M-TAB® Orally Disintegrating Tablet contains 0.42 mg phenylalanine; each 1 mg RISPERDAL® M-TAB® Orally Disintegrating Tablet contains 0.28 mg phenylalanine; and each 0.5 mg RISPERDAL® M-TAB® Orally Disintegrating Tablet contains 0.14 mg phenylalanine.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenesis
Carcinogenicity studies were conducted in Swiss albino mice and Wistar rats. Risperidone was administered in the diet at doses of 0.63 mg/kg, 2.5 mg/kg, and 10 mg/kg for 18 months to mice and for 25 months to rats. These doses are equivalent to approximately 2, 9, and 38 times the maximum recommended human dose (MRHD) for schizophrenia of 16 mg/day on a mg/kg basis or 0.2, 0.75, and 3 times the MRHD (mice) or 0.4, 1.5, and 6 times the MRHD (rats) on a mg/m² body surface basis. A maximum tolerated dose was not achieved in male mice. There were statistically significant increases in pituitary gland adenomas, endocrine pancreas adenomas, and mammary gland adenocarcinomas. The table below summarizes the multiples of the human dose on a mg/m² (mg/kg) basis at which these tumors occurred.
Tumor Type | Species | Sex | Multiples of Maximum Human Dose in mg/m2 (mg/kg) | |
Lowest Effect Level | Highest No-Effect Level | |||
Pituitary adenomas | mouse | female | 0.75 (9.4) | 0.2 (2.4) |
Endocrine pancreas adenomas | rat | male | 1.5 (9.4) | 0.4 (2.4) |
Mammary gland adenocarcinomas | mouse | female | 0.2 (2.4) | none |
rat | female | 0.4 (2.4) | none | |
rat | male | 6.0 (37.5) | 1.5 (9.4) | |
Mammary gland neoplasm, Total | rat | male | 1.5 (9.4) | 0.4 (2.4) |
Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents. Serum prolactin levels were not measured during the risperidone carcinogenicity studies; however, measurements during subchronic toxicity studies showed that risperidone elevated serum prolactin levels 5-6 fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown.
Mutagenesis
No evidence of mutagenic or clastogenic potential for risperidone was found in the Ames gene mutation test, the mouse lymphoma assay, the in vitro rat hepatocyte DNA-repair assay, the in vivo micronucleus test in mice, the sex-linked recessive lethal test in Drosophila, or the chromosomal aberration test in human lymphocytes or Chinese hamster ovary cells.
Impairment Of Fertility
Risperidone (0.16 to 5 mg/kg) was shown to impair mating, but not fertility, in Wistar rats in three reproductive studies (two Segment I and a multigenerational study) at doses 0.1 to 3 times the maximum recommended human dose (MRHD) on a mg/m² body surface area basis. The effect appeared to be in females, since impaired mating behavior was not noted in the Segment I study in which males only were treated. In a subchronic study in Beagle dogs in which risperidone was administered orally at doses of 0.31 to 5 mg/kg, sperm motility and concentration were decreased at doses 0.6 to 10 times the MRHD on a mg/m² body surface area basis. Dose-related decreases were also noted in serum testosterone at the same doses. Serum testosterone and sperm parameters partially recovered, but remained decreased after treatment was discontinued. A no-effect dose could not be determined in either rat or dog.
Use In Specific Populations
Pregnancy
Pregnancy Category C
Risk Summary
Adequate and well controlled studies with RISPERDAL have not been conducted in pregnant women. Neonates exposed to antipsychotic drugs (including RISPERDAL®) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There was no increase in the incidence of malformations in embryo-fetal studies in rats and rabbits at 0.4–6 times MHRD. Increased pup mortality was noted at all doses in peripostnatal studies in rats. RISPERDAL® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Monitor neonates exhibiting extrapyramidal or withdrawal symptoms. Some neonates recover within hours or days without specific treatment; others may require prolonged hospitalization.
Data
Human Data
There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in neonates following in utero exposure to antipsychotics in the third trimester. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
There was one report of a case of agenesis of the cor
When RISPERDAL® is co-administered with enzyme inducers (e.g., carbamazepine), the dose of RISPERDAL® should be increased up to double the patient's usual dose. It may be necessary to decrease the RISPERDAL® dose when enzyme inducers such as carbamazepine are discontinued. Similar effect may be expected with coadministration of RISPERDAL® with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).
When fluoxetine or paroxetine is co-administered with RISPERDAL® , the dose of RISPERDAL® should be reduced. The RISPERDAL® dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, RISPERDAL® should be titrated slowly. It may be necessary to increase the RISPERDAL® dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued.
Administration Of RISPERDAL® Oral Solution
RISPERDAL® Oral Solution can be administered directly from the calibrated pipette, or can be mixed with a beverage prior to administration. RISPERDAL® Oral Solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea.
Directions For Use Of RISPERDAL® M-TAB® Orally Disintegrating Tablets
Tablet Accessing
RISPERDAL®M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg
RISPERDAL® M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are supplied in blister packs of 4 tablets each.
Do not open the blister until ready to administer. For single tablet removal, separate one of the four blister units by tearing apart at the perforations. Bend the corner where indicated. Peel back foil to expose the tablet. DO NOT push the tablet through the foil because this could damage the tablet.
RISPERDAL®M-TAB®Orally Disintegrating Tablets 3 mg and 4 mg
RISPERDAL® M-TAB® Orally Disintegrating Tablets 3 mg and 4 mg are supplied in a child-resistant pouch containing a blister with 1 tablet each.
The child-resistant pouch should be torn open at the notch to access the blister. Do not open the blister until ready to administer. Peel back foil from the side to expose the tablet. DO NOT push the tablet through the foil, because this could damage the tablet.
Tablet Administration
Using dry hands, remove the tablet from the blister unit and immediately place the entire RISPERDAL® M-TAB® Orally Disintegrating Tablet on the tongue. The RISPERDAL® MTAB® Orally Disintegrating Tablet should be consumed immediately, as the tablet cannot be stored once removed from the blister unit. RISPERDAL® M-TAB® Orally Disintegrating Tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.
HOW SUPPLIED
Dosage Forms And Strengths
RISPERDAL® Tablets are available in the following strengths and colors: 0.25 mg (dark yellow), 0.5 mg (red-brown), 1 mg (white), 2 mg (orange), 3 mg (yellow), and 4 mg (green). All are capsule shaped, and imprinted with “JANSSEN” on one side and either “Ris 0.25”, “Ris 0.5”, “R1”, “R2”, “R3”, or “R4” on the other side according to their respective strengths.
RISPERDAL® Oral Solution is available in a 1 mg/mL strength.
RISPERDAL® M-TAB® Orally Disintegrating Tablets are available in the following strengths, colors, and shapes: 0.5 mg (light coral, round), 1 mg (light coral, square), 2 mg (coral, square), 3 mg (coral, round), and 4 mg (coral, round). All are biconvex and etched on one side with “R0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths.
RISPERDAL® (risperidone) Tablets
RISPERDAL® (risperidone) Tablets are imprinted “JANSSEN” on one side and either “Ris 0.25”, “Ris 0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths.
0.25 mg dark yellow, capsule-shaped tablets: bottles of 60 NDC 50458-301-04, bottles of 500 NDC 50458-301-50, and hospital unit dose blister packs of 100 NDC 50458-301-01.
0.5 mg red-brown, capsule-shaped tablets: bottles of 60 NDC 50458-302-06, bottles of 500 NDC 50458-302-50, and hospital unit dose blister packs of 100 NDC 50458-302-01.
1 mg white, capsule-shaped tablets: bottles of 60 NDC 50458-300-06, bottles of 500 NDC 50458-300-50, and hospital unit dose blister packs of 100 NDC 50458-300-01.
2 mg orange, capsule-shaped tablets: bottles of 60 NDC 50458-320-06, bottles of 500 NDC 50458-320-50, and hospital unit dose blister packs of 100 NDC 50458-320-01.
3 mg yellow, capsule-shaped tablets: bottles of 60 NDC 50458-330-06, bottles of 500 NDC 50458-330-50, and hospital unit dose blister packs of 100 NDC 50458-330-01.
4 mg green, capsule-shaped tablets: bottles of 60 NDC 50458-350-06 and hospital unit dose blister packs of 100 NDC 50458-350-01.
RISPERDAL® (risperidone) Oral Solution
RISPERDAL® (risperidone) 1 mg/mL Oral Solution (NDC 50458-305-03) is supplied in 30 mL bottles with a calibrated (in milligrams and milliliters) pipette. The minimum calibrated volume is 0.25 mL, while the maximum calibrated volume is 3 mL.
RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets
RISPERDAL® M-TAB® (risperidone) Orally Disintegrating Tablets are etched on one side with “R0.5”, “R1”, “R2”, “R3”, or “R4” according to their respective strengths. RISPERDAL® MTAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are packaged in blister packs of 4 (2 X 2) tablets. Orally Disintegrating Tablets 3 mg and 4 mg are packaged in a child-resistant pouch containing a blister with 1 tablet.
0.5 mg light coral, round, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-395-28, and long-term care blister packaging of 30 tablets NDC 50458-395-30.
1 mg light coral, square, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-315-28, and long-term care blister packaging of 30 tablets NDC 50458-315-30.
2 mg coral, square, biconvex tablets: 7 blister packages (4 tablets each) per box, NDC 50458-325-28.
3 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-335-28.
4 mg coral, round, biconvex tablets: 28 blisters per box, NDC 50458-355-28.
Storage And Handling
RISPERDAL® Tablets should be stored at controlled room temperature 15°-25°C (59°-77°F). Protect from light and moisture.
RISPERDAL® 1 mg/mL Oral Solution should be stored at controlled room temperature 15°25°C (59°-77°F). Protect from light and freezing.
RISPERDAL® M-TAB® Orally Disintegrating Tablets should be stored at controlled room temperature 15°-25°C (59°-77°F).
Keep out of reach of children.
RISPERDAL® Tablets Active ingredient is made in Ireland Finished product is manufactured by: Janssen Ortho, LLC Gurabo, Puerto Rico 00778. RISPERDAL® Oral Solution Finished product is manufactured by: Janssen Pharmaceutica NV Beerse, Belgium. RISPERDAL® M-TAB® Orally Disintegrating Tablets Active ingredient is made in Ireland Finished product is manufactured by: Janssen Ortho, LLC Gurabo, Puerto Rico 00778. RISPERDAL® Tablets, RISPERDAL® M-TAB® Orally Disintegrating Tablets, and RISPERDAL® Oral Solution are manufactured for: Janssen Pharmaceuticals, Inc. Titusville, NJ 08560. Revised: Mar 2016
Side Effects & Drug InteractionsSIDE EFFECTS
The following are discussed in more detail in other sections of the labeling:
- Increased mortality in elderly patients with dementia-related psychosis
- Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Metabolic Changes (Hyperglycemia and diabetes mellitus, Dyslipidemia, and Weight Gain)
- Hyperprolactinemia
- Orthostatic hypotension
- Leukopenia, neutropenia, and agranulocytosis
- Potential for cognitive and motor impairment
- Seizures
- Dysphagia
- Priapism
- Disruption of body temperature regulation
- Patients with Phenylketonuria.
The most common adverse reactions in clinical trials ( > 5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.
The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in > 1% of adults and/or > 2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness, and akathisia.
The data described in this section are derived from a clinical trial database consisting of 9803 adult and pediatric patients exposed to one or more doses of RISPERDAL® for the treatment of schizophrenia, bipolar mania, autistic disorder, and other psychiatric disorders in pediatrics and elderly patients with dementia. Of these 9803 patients, 2687 were patients who received RISPERDAL® while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with RISPERDAL® 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 3 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs.
Clinical Trials Experience
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.
Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials – Schizophrenia
Adult Patients with Schizophrenia
Table 8 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with schizophrenia in three 4- to 8-week, double-blind, placebo-controlled trials.
Table 8: Adverse Reactions in ≥ 2% of RISPERDAL®-Treated
Adult Patients (and greater than placebo) with Schizophrenia in Double-Blind,
Placebo-Controlled Trials
System/Organ Class Adverse Reaction | Percentage of Patients Reporting Reaction RISPERDAL® | Placebo (N=225) | |
2-8 mg per day (N=366) |
> 8-16 mg per day (N=198) |
||
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 |
* Parkinsonism includes extrapyramidal disorder, musculoskeletal stiffness, parkinsonism, cogwheel rigidity, akinesia, bradykinesia, hypokinesia, masked facies, muscle rigidity, and Parkinson's disease. Akathisia includes akathisia and restlessness. Dystonia includes dystonia, muscle spasms, muscle contractions involuntary, muscle contracture, oculogyration, tongue paralysis. Tremor includes tremor and parkinsonian rest tremor. |
Pediatric Patients with Schizophrenia
Table 9 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with schizophrenia in a 6-week double-blind, placebo-controlled trial.
Table 9: Adverse Reactions in ≥ 5% of
RISPERDAL®-Treated Pediatric Patients (and greater than placebo)
with Schizophrenia in a Double-Blind Trial
System/Organ Class Adverse Reaction | Percentage of Patients Reporting Reaction RISPERDAL® | Placebo (N=54) |
|
1-3 mg per day (N=55) |
4-6 mg per day (N=51) |
||
Gastrointestinal Disorders | |||
Salivary hypersecretion | 0 | 10 | 2 |
Nervous System Disorders | |||
Sedation | 24 | 12 | 4 |
Parkinsonism* | 16 | 28 | 11 |
Tremor | 11 | 10 | 6 |
Akathisia* | 9 | 10 | 4 |
Dizziness | 7 | 14 | 2 |
Dystonia* | 2 | 6 | 0 |
Psychiatric Disorders | |||
Anxiety | 7 | 6 | 0 |
* Parkinsonism includes extrapyramidal disorder, muscle rigidity, musculoskeletal stiffness, and hypokinesia. Akathisia includes akathisia and restlessness. Dystonia includes dystonia and oculogyration. |
Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials – Bipolar Mania
Adult Patients with Bipolar Mania
Table 10 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with bipolar mania in four 3-week, double-blind, placebo-controlled monotherapy trials.
Table 10: Adverse Reactions
in ≥ 2% of RISPERDAL®-Treated Adult Patients (and greater than
placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Monotherapy
Trials
System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Reaction | Placebo (N=424) |
RISPERDAL® 1-6 mg per day (N=448) |
||
Eye Disorders | ||
Vision blurred | 2 | 1 |
Gastrointestinal Disorders | ||
Nausea | 5 | 2 |
Diarrhea | 3 | 2 |
Salivary hypersecretion | 3 | 1 |
Stomach discomfort | 2 | < 1 |
General Disorders | ||
Fatigue | 2 | 1 |
Nervous System Disorders | ||
Parkinsonism* | 25 | 9 |
Sedation | 11 | 4 |
Akathisia* | 9 | 3 |
Tremor* | 6 | 3 |
Dizziness | 6 | 5 |
Dystonia* | 5 | 1 |
Lethargy | 2 | 1 |
* Parkinsonism includes extrapyramidal disorder, parkinsonism, musculoskeletal stiffness, hypokinesia, muscle rigidity, muscle tightness, bradykinesia, cogwheel rigidity. Akathisia includes akathisia and restlessness. Tremor includes tremor and parkinsonian rest tremor. Dystonia includes dystonia, muscle spasms, oculogyration, torticollis. |
Table 11 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with bipolar mania in two 3-week, double-blind, placebo-controlled adjuvant therapy trials.
Table 11: Adverse Reactions in ≥ 2% of RISPERDAL®-Treated
Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind,
Placebo-Controlled Adjunctive Therapy Trials
System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Reaction | |
RISPERDAL® + Mood Stabilizer (N=127) |
Placebo +Mood Stabilizer (N=126) |
|
Cardiac Disorders | ||
Palpitations | 2 | 0 |
Gastrointestinal Disorders | ||
Dyspepsia | 9 | 8 |
Nausea | 6 | 4 |
Diarrhea | 6 | 4 |
Salivary hypersecretion | 2 | 0 |
General Disorders | ||
Chest pain | 2 | 1 |
Infections and Infestations | ||
Urinary tract infection | 2 | 1 |
Nervous System Disorders | ||
Parkinsonism* | 14 | 4 |
Sedation | 9 | 4 |
Akathisia* | 8 | 0 |
Dizziness | 7 | 2 |
Tremor | 6 | 2 |
Lethargy | 2 | 1 |
Psychiatric Disorders | ||
Anxiety | 3 | 2 |
Respiratory, Thoracic and Mediastinal Disorders | ||
Pharyngolaryngeal pain | 5 | 2 |
Cough | 2 | 0 |
* Parkinsonism includes extrapyramidal disorder, hypokinesia and bradykinesia. Akathisia includes hyperkinesia and akathisia. |
Pediatric Patients with Bipolar Mania
Table 12 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with bipolar mania in a 3-week double-blind, placebo-controlled trial.
Table 12: Adverse Reactions
in ≥ 5% of RISPERDAL®-Treated Pediatric Patients (and
greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled
Trials
System/Organ Class Adverse Reaction | Percentage of Patients Reporting Reaction | ||
RISPERDAL ® | Placebo (N=58) |
||
0.5-2.5 mg per day (N=50) |
3-6 mg per day (N=61) |
||
Eye Disorders | |||
Vision blurred | 4 | 7 | 0 |
Gastrointestinal Disorders | |||
Abdominal pain upper | 16 | 13 | 5 |
Nausea | 16 | 13 | 7 |
Vomiting | 10 | 10 | 5 |
Diarrhea | 8 | 7 | 2 |
Dyspepsia | 10 | 3 | 2 |
Stomach discomfort | 6 | 0 | 2 |
General Disorders | |||
Fatigue | 18 | 30 | 3 |
Metabolism and Nutrition Disorders | |||
Increased appetite | 4 | 7 | 2 |
Nervous System Disorders | |||
Sedation | 42 | 56 | 19 |
Dizziness | 16 | 13 | 5 |
Parkinsonism* | 6 | 12 | 3 |
Dystonia* | 6 | 5 | 0 |
Akathisia* | 0 | 8 | 2 |
Psychiatric Disorders | |||
Anxiety | 0 | 8 | 3 |
Respiratory, Thoracic and Mediastinal Disorders | |||
Pharyngolaryngeal pain | 10 | 3 | 5 |
Skin and Subcutaneous Tissue Disorders | |||
Rash | 0 | 7 | 2 |
* Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, bradykinesia, and nuchal rigidity. Dystonia includes dystonia, laryngospasm, and muscle spasms. Akathisia includes restlessness and akathisia. |
Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials - Autistic Disorder
Table 13 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients treated for irritability associated with autistic disorder in two 8-week, double-blind, placebo-controlled trials and one 6-week double-blind, placebo-controlled study.
Table 13: Adverse Reactions in ≥ 5% of
RISPERDAL®-Treated Pediatric Patients (and greater than placebo)
Treated for Irritability Associated with Autistic Disorder in Double-Blind,
Placebo-Controlled Trials
System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Reaction | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RISPERDAL® 0.5-4.0 mg/day (N=107) |
Placebo (N=115) |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gastrointestinal Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vomiting | 20 | 17 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Constipation | 17 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dry mouth | 10 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nausea | 8 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Salivary hypersecretion | 7 | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
General Disorders and Administration Site Conditions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Fatigue | 31 | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pyrexia | 16 | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Thirst | 7 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Infections and Infestations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nasopharyngitis | 19 | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Rhinitis | 9 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Upper respiratory tract infection | 8 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Weight increased | 8 | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Metabolism and Nutrition Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased appetite | 44 | 15 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nervous System Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sedation | 63 | 15 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Drooling | 12 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Headache | 12 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tremor | 8 | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dizziness | 8 | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Parkinsonism* | 8 | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Renal and Urinary Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Enuresis | 16 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Respiratory, Thoracic and Mediastinal Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cough | 17 | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Rhinorrhea | 12 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nasal congestion | 1
Fertility, pregnancy and lactation
Pregnancy Category C Risk SummaryAdequate and well controlled studies with RISPERDAL have not been conducted in pregnant women. Neonates exposed to antipsychotic drugs (including RISPERDAL®) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There was no increase in the incidence of malformations in embryo-fetal studies in rats and rabbits at 0.4–6 times MHRD. Increased pup mortality was noted at all doses in peripostnatal studies in rats. RISPERDAL® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Clinical ConsiderationsFetal/Neonatal Adverse Reactions Monitor neonates exhibiting extrapyramidal or withdrawal symptoms. Some neonates recover within hours or days without specific treatment; others may require prolonged hospitalization. DataHuman Data There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in neonates following in utero exposure to antipsychotics in the third trimester. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. There was one report of a case of agenesis of the corpus callosum in an infant exposed to risperidone in utero. The causal relationship to RISPERDAL® therapy is unknown. Animal Data The teratogenic potential of risperidone was studied in three Segment II studies in Sprague-Dawley and Wistar rats (0.63-10 mg/kg or 0.4 to 6 times the maximum recommended human dose [MRHD] on a mg/m² body surface area basis) and in one Segment II study in New Zealand rabbits (0.31-5 mg/kg or 0.4 to 6 times the MRHD on a mg/m² body surface area basis). There were no teratogenic effects in offspring of rats or rabbits given 0.4 to 6 times the MRHD on a mg/m² body surface area basis. In three reproductive studies in rats (two Segment III and a multigenerational study), there was an increase in pup deaths during the first 4 days of lactation at doses of 0.16-5 mg/kg or 0.1 to 3 times the MRHD on a mg/m² body surface area basis. It is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams. There was no no-effect dose for increased rat pup mortality. In one Segment III study, there was an increase in stillborn rat pups at a dose of 2.5 mg/kg or 1.5 times the MRHD on a mg/m² body surface area basis. In a cross-fostering study in Wistar rats, toxic effects on the fetus or pups were observed, as evidenced by a decrease in the number of live pups and an increase in the number of dead pups at birth (Day 0), and a decrease in birth weight in pups of drug-treated dams. In addition, there was an increase in deaths by Day 1 among pups of drug-treated dams, regardless of whether or not the pups were cross-fostered. Risperidone also appeared to impair maternal behavior in that pup body weight gain and survival (from Day 1 to 4 of lactation) were reduced in pups born to control but reared by drug-treated dams. These effects were all noted at the one dose of risperidone tested, i.e., 5 mg/kg or 3 times the MRHD on a mg/m² body surface area basis. Placental transfer of risperidone occurs in rat pups. Undesirable effects
The following are discussed in more detail in other sections of the labeling:
The most common adverse reactions in clinical trials ( > 5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in > 1% of adults and/or > 2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness, and akathisia. The data described in this section are derived from a clinical trial database consisting of 9803 adult and pediatric patients exposed to one or more doses of RISPERDAL® for the treatment of schizophrenia, bipolar mania, autistic disorder, and other psychiatric disorders in pediatrics and elderly patients with dementia. Of these 9803 patients, 2687 were patients who received RISPERDAL® while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with RISPERDAL® 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 3 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs. Clinical Trials ExperienceBecause 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. Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials – SchizophreniaAdult Patients with SchizophreniaTable 8 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with schizophrenia in three 4- to 8-week, double-blind, placebo-controlled trials. Table 8: Adverse Reactions in ≥ 2% of RISPERDAL®-Treated
Adult Patients (and greater than placebo) with Schizophrenia in Double-Blind,
Placebo-Controlled Trials
Pediatric Patients with SchizophreniaTable 9 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with schizophrenia in a 6-week double-blind, placebo-controlled trial. Table 9: Adverse Reactions in ≥ 5% of
RISPERDAL®-Treated Pediatric Patients (and greater than placebo)
with Schizophrenia in a Double-Blind Trial
Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials – Bipolar ManiaAdult Patients with Bipolar ManiaTable 10 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with bipolar mania in four 3-week, double-blind, placebo-controlled monotherapy trials. Table 10: Adverse Reactions
in ≥ 2% of RISPERDAL®-Treated Adult Patients (and greater than
placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Monotherapy
Trials
Table 11 lists the adverse reactions reported in 2% or more of RISPERDAL®-treated adult patients with bipolar mania in two 3-week, double-blind, placebo-controlled adjuvant therapy trials. Table 11: Adverse Reactions in ≥ 2% of RISPERDAL®-Treated
Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind,
Placebo-Controlled Adjunctive Therapy Trials
Pediatric Patients with Bipolar ManiaTable 12 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients with bipolar mania in a 3-week double-blind, placebo-controlled trial. Table 12: Adverse Reactions
in ≥ 5% of RISPERDAL®-Treated Pediatric Patients (and
greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled
Trials
Commonly-Observed Adverse Reactions In Double-Blind, Placebo-Controlled Clinical Trials - Autistic DisorderTable 13 lists the adverse reactions reported in 5% or more of RISPERDAL®-treated pediatric patients treated for irritability associated with autistic disorder in two 8-week, double-blind, placebo-controlled trials and one 6-week double-blind, placebo-controlled study. Table 13: Adverse Reactions in ≥ 5% of
RISPERDAL®-Treated Pediatric Patients (and greater than placebo)
Treated for Irritability Associated with Autistic Disorder in Double-Blind,
Placebo-Controlled Trials
Other Adverse Reactions Observed During The Clinical Trial Evaluation Of RisperidoneThe following additional adverse reactions occurred across all placebo-controlled, active-controlled, and open-label studies of RISPERDAL® in adults and pediatric patients. Blood and Lymphatic System Disorders: anemia, granulocytopenia, neutropenia Cardiac Disorders: sinus bradycardia, sinus tachycardia, atrioventricular block first degree, bundle branch block left, bundle branch block right, atrioventricular block Ear and Labyrinth Disorders: ear pain, tinnitus Endocrine Disorders: hyperprolactinemia Eye Disorders: ocular hyperemia, eye discharge, conjunctivitis, eye rolling, eyelid edema, eye swelling, eyelid margin crusting, dry eye, lacrimation increased, photophobia, glaucoma, visual acuity reduced Gastrointestinal Disorders: dysphagia, fecaloma, fecal incontinence, gastritis, lip swelling, cheilitis, aptyalism General Disorders: edema peripheral, thirst, gait disturbance, influenza-like illness, pitting edema, edema, chills, sluggishness, malaise, chest discomfort, face edema, discomfort, generalized edema, drug withdrawal syndrome, peripheral coldness, feeling abnormal Immune System Disorders: drug hypersensitivity Infections and Infestations: pneumonia, influenza, ear infection, viral infection, pharyngitis, tonsillitis, bronchitis, eye infection, localized infection, cystitis, cellulitis, otitis media, onychomycosis, acarodermatitis, bronchopneumonia, respiratory tract infection, tracheobronchitis, otitis media chronic Investigations: body temperature increased, blood prolactin increased, alanine aminotransferase increased, electrocardiogram abnormal, eosinophil count increased, white blood cell count decreased, blood glucose increased, hemoglobin decreased, hematocrit decreased, body temperature decreased, blood pressure decreased, transaminases increased Metabolism and Nutrition Disorders: decreased appetite, polydipsia, anorexia Musculoskeletal and Connective Tissue Disorders: joint stiffness, joint swelling, musculoskeletal chest pain, posture abnormal, myalgia, neck pain, muscular weakness, rhabdomyolysis Nervous System Disorders: balance disorder, disturbance in attention, dysarthria, unresponsive to stimuli, depressed level of consciousness, movement disorder, transient ischemic attack, coordination abnormal, cerebrovascular accident, speech disorder, syncope, loss of consciousness, hypoesthesia, tardive dyskinesia, dyskinesia, cerebral ischemia, cerebrovascular disorder, neuroleptic malignant syndrome, diabetic coma, head titubation Psychiatric Disorders: agitation, blunted affect, confusional state, middle insomnia, nervousness, sleep disorder, listlessness, libido decreased, and anorgasmia Renal and Urinary Disorders: enuresis, dysuria, pollakiuria, urinary incontinence Reproductive System and Breast Disorders: menstruation irregular, amenorrhea, gynecomastia, galactorrhea, vaginal discharge, menstrual disorder, erectile dysfunction, retrograde ejaculation, ejaculation disorder, sexual dysfunction, breast enlargement Respiratory, Thoracic, and Mediastinal Disorders: wheezing, pneumonia aspiration, sinus congestion, dysphonia, productive cough, pulmonary congestion, respiratory tract congestion, rales, respiratory disorder, hyperventilation, nasal edema Skin and Subcutaneous Tissue Disorders: erythema, skin discoloration, skin lesion, pruritus, skin disorder, rash erythematous, rash papular, rash generalized, rash maculopapular, acne, hyperkeratosis, seborrheic dermatitis Vascular Disorders: hypotension, flushing Additional Adverse Reactions Reported With RISPERDAL® CONSTA®The following is a list of additional adverse reactions that have been reported during the premarketing evaluation of RISPERDAL® CONSTA®, regardless of frequency of occurrence: Cardiac Disorders: bradycardia Ear and Labyrinth Disorders: vertigo Eye Disorders: blepharospasm Gastrointestinal Disorders: toothache, tongue spasm General Disorders and Administration Site Conditions: pain Infections and Infestations: lower respiratory tract infection, infection, gastroenteritis, subcutaneous abscess Injury and Poisoning: fall Investigations: weight decreased, gamma-glutamyltransferase increased, hepatic enzyme increased Musculoskeletal, Connective Tissue, and Bone Disorders: buttock pain Nervous System Disorders: convulsion, paresthesia Psychiatric Disorders: depression Skin and Subcutaneous Tissue Disorders: eczema Vascular Disorders: hypertension Discontinuations Due To Adverse ReactionsSchizophrenia - AdultsApproximately 7% (39/564) of RISPERDAL®-treated patients in double-blind, placebo-controlled trials discontinued treatment due to an adverse reaction, compared with 4% (10/225) who were receiving placebo. The adverse reactions associated with discontinuation in 2 or more RISPERDAL®-treated patients were: Table 14: Adverse Reactions Associated With
Discontinuation in 2 or More RISPERDAL®Treated Adult Patients in
Schizophrenia Trials
Discontinuation for extrapyramidal symptoms (including Parkinsonism, akathisia, dystonia, and tardive dyskinesia) was 1% in placebo-treated patients, and 3.4% in active control-treated patients in a double-blind, placebo- and active-controlled trial. Schizophrenia - PediatricsApproximately 7% (7/106), of RISPERDAL®-treated patients discontinued treatment due to an adverse reaction in a double-blind, placebo-controlled trial, compared with 4% (2/54) placebo-treated patients. The adverse reactions associated with discontinuation for at least one RISPERDAL®-treated patient were dizziness (2%), somnolence (1%), sedation (1%), lethargy (1%), anxiety (1%), balance disorder (1%), hypotension (1%), and palpitation (1%). Bipolar Mania - AdultsIn double-blind, placebo-controlled trials with RISPERDAL® as monotherapy, approximately 6% (25/448) of RISPERDAL®-treated patients discontinued treatment due to an adverse event, compared with approximately 5% (19/424) of placebo-treated patients. The adverse reactions associated with discontinuation in RISPERDAL®-treated patients were: Table 15: Adverse Reactions Associated With Discontinuation in 2 or More RISPERDAL®Treated Adult Patients in Bi Overdose
Human ExperiencePremarketing experience included eight reports of acute RISPERDAL® 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 includes reports of acute RISPERDAL® overdosage, 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 RISPERDAL® overdose include prolonged QT interval and convulsions. Torsade de pointes has been reported in association with combined overdose of RISPERDAL® and paroxetine. Management Of OverdosageFor the most up to date information on the management of RISPERDAL® overdosage, contact a certified poison control center (1-800-222-1222 or www.poison.org). Provide supportive care including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures. There is no specific antidote to RISPERDAL®. Pharmacodynamic properties
RISPERDAL® is a selective monoaminergic antagonist with high affinity (Ki of 0.12 to 7.3 nM) for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), α1 and α2 adrenergic, and H1 histaminergic receptors. RISPERDAL® acts as an antagonist at other receptors, but with lower potency. RISPERDAL® has low to moderate affinity (Ki of 47 to 253 nM) for the serotonin 5HT1C, 5HT1D, and 5HT1A receptors, weak affinity (Ki of 620 to 800 nM) for the dopamine D1 and haloperidol-sensitive sigma site, and no affinity (when tested at concentrations > 10-5 M) for cholinergic muscarinic or β1 and β2 adrenergic receptors. Pharmacokinetic properties
AbsorptionRisperidone is well absorbed. The absolute oral bioavailability of risperidone is 70% (CV=25%). The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) when compared to a solution. Pharmacokinetic studies showed that RISPERDAL® M-TAB® Orally Disintegrating Tablets and RISPERDAL® Oral Solution are bioequivalent to RISPERDAL® Tablets. Plasma concentrations of risperidone, its major metabolite, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone are dose proportional over the dosing range of 1 to 16 mg daily (0.5 to 8 mg twice daily). Following oral administration of solution or tablet, mean peak plasma concentrations of risperidone occurred at about 1 hour. Peak concentrations of 9-hydroxyrisperidone occurred at about 3 hours in extensive metabolizers, and 17 hours in poor metabolizers. Steady-state concentrations of risperidone are reached in 1 day in extensive metabolizers and would be expected to reach steady-state in about 5 days in poor metabolizers. Steady-state concentrations of 9-hydroxyrisperidone are reached in 5-6 days (measured in extensive metabolizers). Food Effect Food does not affect either the rate or extent of absorption of risperidone. Thus, RISPERDAL® can be given with or without meals. DistributionRisperidone is rapidly distributed. The volume of distribution is 1-2 L/kg. In plasma, risperidone is bound to albumin and α1-acid glycoprotein. The plasma protein binding of risperidone is 90%, and that of its major metabolite, 9-hydroxyrisperidone, is 77%. Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine (100 mcg/mL), warfarin (10 mcg/mL), and carbamazepine (10mcg/mL) caused only a slight increase in the free fraction of risperidone at 10 ng/mL and 9-hydroxyrisperidone at 50 ng/mL, changes of unknown clinical significance. MetabolismRisperidone is extensively metabolized in the liver. The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N-dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone. Consequently, the clinical effect of the drug results from the combined concentrations of risperidone plus 9-hydroxyrisperidone. CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP 2D6 is subject to genetic polymorphism (about 6%-8% of Caucasians, and a very low percentage of Asians, have little or no activity and are “poor metabolizers”) and to inhibition by a variety of substrates and some non-substrates, notably quinidine. Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, are similar in extensive and poor metabolizers. Risperidone could be subject to two kinds of drug-drug interactions. First, inhibitors of CYP 2D6 interfere with conversion of risperidone to 9-hydroxyrisperidone. This occurs with quinidine, giving essentially all recipients a risperidone pharmacokinetic profile typical of poor metabolizers. The therapeutic benefits and adverse effects of risperidone in patients receiving quinidine have not been evaluated, but observations in a modest number (n≅70) of poor metabolizers given RISPERDAL® do not suggest important differences between poor and extensive metabolizers. Second, co-administration of known enzyme inducers (e.g., carbamazepine, phenytoin, rifampin, and phenobarbital) with RISPERDAL® may cause a decrease in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone. It would also be possible for risperidone to interfere with metabolism of other drugs metabolized by CYP 2D6. Relatively weak binding of risperidone to the enzyme suggests this is unlikely. In vitro studies indicate that risperidone is a relatively weak inhibitor of CYP 2D6. Therefore, RISPERDAL® is not expected to substantially inhibit the clearance of drugs that are metabolized by this enzymatic pathway. In drug interaction studies, RISPERDAL® did not significantly affect the pharmacokinetics of donepezil and galantamine, fwhich are metabolized by CYP 2D6. In vitro studies demonstrated that drugs metabolized by other CYP isozymes, including 1A1, 1A2, 2C9, 2C19, and 3A4, are only weak inhibitors of risperidone metabolism. ExcretionRisperidone and its metabolites are eliminated via the urine and, to a much lesser extent, via the feces. As illustrated by a mass balance study of a single 1 mg oral dose of 14C-risperidone administered as solution to three healthy male volunteers, total recovery of radioactivity at 1 week was 84%, including 70% in the urine and 14% in the feces. The apparent half-life of risperidone was 3 hours (CV=30%) in extensive metabolizers and 20 hours (CV=40%) in poor metabolizers. The apparent half-life of 9-hydroxyrisperidone was about 21 hours (CV=20%) in extensive metabolizers and 30 hours (CV=25%) in poor metabolizers. The pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, were similar in extensive and poor metabolizers, with an overall mean elimination half-life of about 20 hours. Date of revision of the text
Mar 2016
Risperdal 1% price We have no data on the cost of the drug. However, we will provide data for each active ingredient The approximate cost of Risperidone 2 mg per unit in online pharmacies is from 0.2$ to 1.79$, per package is from 26$ to 179$. The approximate cost of Risperidone 0.25 mg per unit in online pharmacies is from 0.25$ to 0.92$, per package is from 25$ to 92$. The approximate cost of Risperidone 0.5 mg per unit in online pharmacies is from 0.19$ to 1.15$, per package is from 21$ to 111$. The approximate cost of Risperidone 1 mg per unit in online pharmacies is from 0.27$ to 1.35$, per package is from 27$ to 135$. The approximate cost of Risperidone 1 mg/ml per unit in online pharmacies is from 0.8$ to 2.67$, per package is from 51$ to 174$. The approximate cost of Risperidone 3 mg per unit in online pharmacies is from 0.36$ to 2.34$, per package is from 28$ to 234$. The approximate cost of Risperidone 4 mg per unit in online pharmacies is from 0.38$ to 3.05$, per package is from 30$ to 305$.
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