Risperidone
Gen-Source Rx
Aurolife Pharma LLC
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use risperidone safely and effectively. See full prescribing information for risperidone tablets.Risperidone Tablets, USPInitial U.S. Approval: 1993 BOXED WARNING WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperidone is not approved for use in patients with dementia-related psychosis. (5.1) INDICATIONS AND USAGERisperidone is an atypical antipsychotic agent indicated for: Treatment of schizophrenia in adults (1.1) Alone, or in combination with lithium or valproate, for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in adults (1.2) Treatment of irritability associated with autistic disorder in children and adolescents aged 5 to 16 years (1.3) Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia or bipolar mania. (1.1, 1.2) DOSAGE AND ADMINISTRATION InitialDose Titration TargetDose EffectiveDose Range Schizophrenia- adults (2.1) 2 mg/day 1 to 2 mg daily 4 to 8 mgdaily 4 to 16 mg/day Bipolar mania– adults (2.2) 2 to 3 mg/day 1 mg daily 1 to 6 mg/day 1 to 6 mg/day Irritability Associated with autistic disorder (2.3) 0.25 mg/day (
FULL PRESCRIBING INFORMATION: CONTENTS*
- WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
- 1 RISPERIDONE INDICATIONS AND USAGE
- 2 RISPERIDONE DOSAGE AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 RISPERIDONE CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis
- 5.2 Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
- 5.3 Neuroleptic Malignant Syndrome (NMS)
- 5.4 Tardive Dyskinesia
- 5.5 Hyperglycemia and Diabetes Mellitus
- 5.6 Hyperprolactinemia
- 5.7 Orthostatic Hypotension
- 5.8 Leukopenia, Neutropenia, and Agranulocytosis
- 5.9 Potential for Cognitive and Motor Impairment
- 5.10 Seizures
- 5.11 Dysphagia
- 5.12 Priapism
- 5.13 Thrombotic Thrombocytopenic Purpura (TTP)
- 5.14 Body Temperature Regulation
- 5.15 Antiemetic Effect
- 5.16 Suicide
- 5.17 Use in Patients with Concomitant Illness
- 5.18 Monitoring: Laboratory Tests
- 6 RISPERIDONE ADVERSE REACTIONS
- 6.1 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Schizophrenia
- 6.2 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Bipolar Mania
- 6.3 Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials - Autistic Disorder
- 6.4 Other Adverse Reactions Observed During the Premarketing Evaluation of Risperidone
- 6.5 Discontinuations Due to Adverse Reactions
- 6.6 Dose Dependency of Adverse Reactions in Clinical Trials
- 6.7 Changes in Body Weight
- 6.8 Changes in ECG
- 6.9 Postmarketing Experience
- 7 DRUG INTERACTIONS
- 7.1 Centrally-Acting Drugs and Alcohol
- 7.2 Drugs with Hypotensive Effects
- 7.3 Levodopa and Dopamine Agonists
- 7.4 Amitriptyline
- 7.5 Cimetidine and Ranitidine
- 7.6 Clozapine
- 7.7 Lithium
- 7.8 Valproate
- 7.9 Digoxin
- 7.10 Drugs That Inhibit CYP 2D6 and Other CYP Isozymes
- 7.11 Carbamazepine and Other Enzyme Inducers
- 7.12 Drugs Metabolized by CYP 2D6
- 8 USE IN SPECIFIC POPULATIONS
- 9 DRUG ABUSE AND DEPENDENCE
- 10 OVERDOSAGE
- 11 RISPERIDONE DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 0.25 mg (500 Tablet Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 0.5 mg (500 Tablet Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 1 mg (500 Tablet Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 2 mg (500 Tablet Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 3 mg (500 Tablet Bottle)
- PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg (60 Tablet Bottle)
FULL PRESCRIBING INFORMATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Risperidone is not approved for the treatment of patients with dementia-related psychosis. [See Warnings and Precautions ( 5.1 )]
1 INDICATIONS AND USAGE
1.1 Schizophrenia
[see Clinical Studies (14.1)]
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia. Pediatric use information for the treatment of pediatric patients with schizophrenia, 13 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
1.2 Bipolar Mania
[see Clinical Studies (14.2)]
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with bipolar mania. Pediatric use information for the treatment of pediatric patients with bipolar mania, 10 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
[see Clinical Studies (14.3)]
1.3 Irritability Associated with Autistic Disorder
[see Clinical Studies (14.4)]
2 DOSAGE AND ADMINISTRATION
2.1 Schizophrenia
[see Clinical Studies (14.1)]
[see Clinical Studies (14.1)]
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia. Dosage and administration information for pediatric patients with schizophrenia, 13 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug product.
2.2 Bipolar Mania
[see Clinical Studies (14.2 14.3)]
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with bipolar mania. Dosage and administration information for the treatment of pediatric patients with bipolar disorder is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)
[see Clinical Studies (14.4)]
2.4 Dosage in Special Populations
[see Clinical Pharmacology (12.3)][see Warnings and Precautions (5.2 5.7 5.17)]
2.5 Coadministration of Risperidone with Certain Other Medications
[see Drug Interactions (7.11)]
[see Drug Interactions (7.10)]
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 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. Risperidone is not approved for the treatment of dementia-related psychosis [see Boxed Warning].
5.2 Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients with Dementia-Related Psychosis
[See also Boxed Warnings and Warnings and Precautions (5.1)]
5.3 Neuroleptic Malignant Syndrome (NMS)
5.4 Tardive Dyskinesia
5.5 Hyperglycemia and Diabetes Mellitus
5.6 Hyperprolactinemia
2
in vitro[see Non-Clinical Toxicology (13.1)]
5.7 Orthostatic Hypotension
[see Dosage and Administration (2.1 2.4)]
5.8 Leukopenia, Neutropenia, and Agranulocytosis
Class Effect:
3
5.9 Potential for Cognitive and Motor Impairment
5.10 Seizures
5.11 Dysphagia
[See also Boxed Warning and Warnings and Precautions (5.1)]
5.12 Priapism
[see Adverse Reactions (6.9)]
5.13 Thrombotic Thrombocytopenic Purpura (TTP)
5.14 Body Temperature Regulation
5.15 Antiemetic Effect
5.16 Suicide
5.17 Use in Patients with Concomitant Illness
2[see Dosage and Administration (2.4)]
5.18 Monitoring: Laboratory Tests
6 ADVERSE REACTIONS
- Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1)]
- Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2)]
- Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
- Tardive dyskinesia [see Warnings and Precautions (5.4)]
- Hyperglycemia and diabetes mellitus [see Warnings and Precautions (5.5)]
- Hyperprolactinemia [see Warnings and Precautions (5.6)]
- Orthostatic hypotension [see Warnings and Precautions (5.7)]
- Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.8)]
- Potential for cognitive and motor impairment [see Warnings and Precautions (5.9)]
- Seizures [see Warnings and Precautions (5.10)]
- Dysphagia [see Warnings and Precautions (5.11)]
- Priapism [see Warnings and Precautions (5.12)]
- Thrombotic Thrombocytopenic Purpura (TTP) [see Warnings and Precautions (5.13)]
- Disruption of body temperature regulation [see Warnings and Precautions (5.14)]
- Antiemetic effect [see Warnings and Precautions (5.15)]
- Suicide [see Warnings and Precautions (5.16)]
- Increased sensitivity in patients with Parkinson’s disease or those with dementia with Lewy bodies [see Warnings and Precautions (5.17)]
- Diseases or conditions that could affect metabolism or hemodynamic responses [see Warnings and Precautions (5.17)]
[see Adverse Reactions (6.5)]
6.1 Commonly-Observed Side Effects in Double-Blind, Placebo-Controlled Clinical Trials – Schizophrenia
Adult Patients with Schizophrenia
|
System/Organ Class
Adverse Reaction |
Percentage of Patients Reporting Event | ||
|---|---|---|---|
| Risperidone | |||
| 2 to 8 mg per day (N=366) |
>8 to 16 mg per day (N=198) |
Placebo (N=225) |
|
| * 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. Dyskinesia includes dyskinesia, muscle twitching, chorea, and choreoathetosis. |
|||
|
Blood and Lymphatic System Disorders
|
|
|
|
| Anemia |
<1 |
1 |
0 |
|
Cardiac Disorders
|
|||
| Tachycardia |
1 |
3 |
0 |
|
Ear and Labyrinth Disorders
|
|||
| Ear pain |
<1 |
1 |
0 |
| Eye Disorders
|
|||
| Vision blurred |
3 |
1 |
1 |
|
Gastrointestinal Disorders
|
|||
| Nausea |
9 |
4 |
4 |
| Constipation |
8 |
9 |
6 |
| Dyspepsia |
8 |
6 |
5 |
| Vomiting |
7 |
5 |
7 |
| Dry mouth |
4 |
0 |
1 |
| Abdominal discomfort |
3 |
1 |
1 |
| Salivary hypersecretion |
2 |
1 |
<1 |
| Diarrhea |
2 |
1 |
1 |
| Abdominal pain |
1 |
1 |
0 |
| Abdominal pain upper |
1 |
1 |
0 |
| Stomach discomfort |
1 |
1 |
1 |
|
General Disorders
|
|||
| Fatigue |
3 |
1 |
0 |
| Chest pain |
2 |
2 |
1 |
| Asthenia |
2 |
1 |
<1 |
|
Immune System Disorders
|
|||
| Hypersensitivity |
<1 |
1 |
0 |
|
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
|
|||
| Weight increased |
1 |
1 |
0 |
| Blood creatine phosphokinase increased |
1 |
2 |
<1 |
| Heart rate increased |
<1 |
2 |
0 |
|
Metabolism and Nutrition Disorders
|
|||
| Decreased appetite |
1 |
0 |
<1 |
|
Musculoskeletal and Connective Tissue Disorders
|
|||
| Back pain |
4 |
1 |
1 |
| Arthralgia |
2 |
3 |
<1 |
| Pain in extremity |
2 |
1 |
1 |
| Joint stiffness |
1 |
1 |
0 |
|
Nervous System Disorders
|
|||
| Parkinsonism* |
14 |
17 |
8 |
| Akathisia* |
10 |
10 |
3 |
| Dizziness |
7 |
4 |
2 |
| Somnolence |
7 |
2 |
1 |
| Dystonia* |
3 |
4 |
2 |
| Sedation |
3 |
3 |
1 |
| Tremor* |
2 |
3 |
1 |
| Dizziness postural |
2 |
0 |
0 |
| Dyskinesia* |
1 |
2 |
2 |
| Syncope |
1 |
1 |
0 |
|
Psychiatric Disorders
|
|||
| Insomnia |
32 |
25 |
27 |
| Anxiety |
16 |
11 |
11 |
| Nervousness |
1 |
1 |
<1 |
|
Renal and Urinary Disorders
|
|||
| Urinary incontinence |
1 |
1 |
0 |
|
Reproductive System and Breast Disorders
|
|||
| Ejaculation failure |
<1 |
1 |
0 |
|
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 |
| Dandruff |
1 |
1 |
0 |
| Seborrheic dermatitis |
<1 |
1 |
0 |
| Hyperkeratosis |
0 |
1 |
1 |
|
Vascular Disorders
|
|||
| Orthostatic hypotension |
2 |
1 |
0 |
| Hypotension |
1 |
1 |
0 |
Pediatric Patients with Schizophrenia
| System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Event | ||
|---|---|---|---|
| Risperidone | |||
| 1 to 3 mg per day (N=55) |
4 to 6 mg per day (N=51) |
Placebo (N=54) |
|
| * Parkinsonism includes extrapyramidal disorder, muscle rigidity, musculoskeletal stiffness, and hypokinesia. Akathisia includes akathisia and restlessness. Dystonia includes dystonia and oculogyration. |
|||
|
Gastrointestinal Disorders
|
|
|
|
| Salivary hypersecretion |
0 |
10 |
2 |
|
Nervous System Disorders
|
|||
| Parkinsonism* |
16 |
28 |
11 |
| Sedation |
13 |
8 |
2 |
| Somnolence |
11 |
4 |
2 |
| Tremor |
11 |
10 |
6 |
| Akathisia* |
9 |
10 |
4 |
| Dizziness |
7 |
14 |
2 |
| Dystonia* |
2 |
6 |
0 |
|
Psychiatric Disorders
|
|||
| Anxiety |
7 |
6 |
0 |
6.2 Commonly-Observed Side Effects in Double-Blind, Placebo-Controlled Clinical Trials – Bipolar Mania
Adult Patients with Bipolar Mania
| System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Event | |
|---|---|---|
| Risperidone 1 to 6 mg per day (N=448) |
Placebo (N=424) |
|
| * 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. Dyskinesia includes muscle twitching and dyskinesia. |
||
|
Cardiac Disorders
|
||
| Tachycardia |
1 |
<1 |
|
Eye Disorders
|
||
| Vision blurred |
2 |
1 |
|
Gastrointestinal Disorders
|
||
| Nausea |
5 |
2 |
| Diarrhea |
3 |
2 |
| Salivary hypersecretion |
3 |
1 |
| Dyspepsia |
2 |
2 |
| Stomach discomfort |
2 |
<1 |
|
General Disorders
|
||
| Fatigue |
2 |
1 |
| Asthenia |
1 |
1 |
| Pyrexia |
1 |
1 |
|
Infections and Infestations
|
||
| Nasopharyngitis |
1 |
1 |
|
Investigations
|
||
| Aspartate aminotransferase increased |
1 |
<1 |
|
Nervous System Disorders
|
||
| Parkinsonism* |
25 |
9 |
| Akathisia* |
9 |
3 |
| Tremor* |
6 |
3 |
| Dizziness |
6 |
5 |
| Sedation |
6 |
2 |
| Somnolence |
5 |
2 |
| Dystonia* |
5 |
1 |
| Lethargy |
2 |
1 |
| Dyskinesia* |
1 |
<1 |
|
Reproductive System and Breast Disorders
|
||
| Galactorrhea |
1 |
0 |
|
Skin and Subcutaneous Tissue Disorders
|
||
| Acne |
1 |
0 |
| System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Event | |
|---|---|---|
| Risperidone + Mood Stabilizer (N=127) |
Placebo + Mood Stabilizer (N=126) |
|
| * Parkinsonism includes extrapyramidal disorder, hypokinesia and bradykinesia. Akathisia includes hyperkinesia and akathisia. |
||
|
Cardiac Disorders
|
||
| Palpitations |
2 |
0 |
|
Gastrointestinal Disorders
|
||
| Dyspepsia |
9 |
8 |
| Nausea |
6 |
4 |
| Diarrhea |
6 |
4 |
| Dry mouth |
4 |
4 |
| Vomiting |
4 |
6 |
| Constipation |
3 |
3 |
| Salivary hypersecretion |
2 |
0 |
|
General Disorders
|
||
| Chest pain |
2 |
1 |
| Fatigue |
2 |
2 |
|
Infections and Infestations
|
||
| Nasopharyngitis |
2 |
3 |
| Urinary tract infection |
2 |
1 |
|
Investigations
|
||
| Weight increased |
2 |
2 |
|
Nervous System Disorders
|
||
| Parkinsonism* |
14 |
4 |
| Headache |
14 |
15 |
| Akathisia* |
8 |
0 |
| Dizziness |
7 |
2 |
| Sedation |
6 |
3 |
| Tremor |
6 |
2 |
| Somnolence |
3 |
1 |
| Lethargy |
2 |
1 |
|
Psychiatric Disorders
|
||
| Insomnia |
4 |
8 |
| Anxiety |
3 |
2 |
|
Respiratory, Thoracic and Mediastinal Disorders
|
||
| Pharyngolaryngeal pain |
5 |
2 |
| Cough |
2 |
0 |
Pediatric Patients with Bipolar Mania
|
System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Event | ||
|---|---|---|---|
| Risperidone | |||
| 0.5 to 2.5 mg per day (N=50) |
3 to 6 mg per day (N=61) |
Placebo (N=58) |
|
| * Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, bradykinesia, and nuchal rigidity. Dystonia includes dystonia, laryngospasm, and muscle spasms. Akathisia includes restlessness and akathisia. |
|||
|
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
|
|||
| Somnolence |
22 |
30 |
12 |
| Sedation |
20 |
23 |
7 |
| 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 |
6.3 Commonly-Observed Side Effects in Double-Blind, Placebo-Controlled Clinical Trials - Autistic Disorder
| System/Organ Class Adverse Reaction |
Percentage of Patients Reporting Event | |
|---|---|---|
| Risperidone 0.5 to 4 mg per day (N=76) |
Placebo (N=80) |
|
| * Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, muscle rigidity, cogwheel rigidity, and muscle tightness. |
||
|
Cardiac Disorders
|
||
| Tachycardia |
5 |
0 |
|
Gastrointestinal Disorders
|
||
| Vomiting |
25 |
21 |
| Constipation |
21 |
8 |
| Dry mouth |
15 |
6 |
| Salivary hypersecretion |
9 |
0 |
| Nausea |
8 |
6 |
|
General Disorders
|
||
| Fatigue |
42 |
13 |
| Feeling abnormal |
5 |
0 |
|
Infections and Infestations
|
||
| Nasopharyngitis |
21 |
10 |
| Rhinitis |
13 |
10 |
| Upper respiratory tract infection |
8 |
3 |
|
Investigations
|
||
| Weight increased |
5 |
0 |
|
Metabolism and Nutrition Disorders
|
||
| Increased appetite |
47 |
19 |
|
Nervous System Disorders
|
||
| Somnolence |
49 |
18 |
| Sedation |
29 |
3 |
| Drooling |
16 |
5 |
| Tremor |
12 |
1 |
| Parkinsonism* |
11 |
1 |
| Dizziness |
9 |
3 |
| Dyskinesia |
7 |
3 |
| Lethargy |
5 |
3 |
|
Respiratory, Thoracic and Mediastinal Disorders
|
||
| Cough |
24 |
18 |
| Rhinorrhea |
16 |
13 |
| Nasal congestion |
13 |
5 |
|
Skin and Subcutaneous Tissue Disorders
|
||
| Rash |
11 |
8 |
6.4 Other Side Effects Observed During the Premarketing Evaluation of Risperidone
6.5 Discontinuations Due to Side Effects
| Adverse Reaction | Risperidone | ||
|---|---|---|---|
| 2 to 8 mg/day (N=366) |
>8 to 16 mg/day (N=198) |
Placebo (N=225) |
|
| Dizziness |
1.4% |
1% |
0% |
| Nausea |
1.4% |
0% |
0% |
| Vomiting |
0.8% |
0% |
0% |
| Parkinsonism |
0.8% |
0% |
0% |
| Somnolence |
0.8% |
0% |
0% |
| Dystonia |
0.5% |
0% |
0% |
| Agitation |
0.5% |
0% |
0% |
| Abdominal pain |
0.5% |
0% |
0% |
| Orthostatic hypotension |
0.3% |
0.5% |
0% |
| Akathisia |
0.3% |
2% |
0% |
| Adverse Reaction | Risperidone 1 to 6 mg/day (N=448) |
Placebo (N=424) |
|---|---|---|
| Parkinsonism |
0.4% |
0% |
| Lethargy |
0.2% |
0% |
| Dizziness |
0.2% |
0% |
| Alanine aminotransferase increased |
0.2% |
0.2% |
| Aspartate aminotransferase increased |
0.2% |
0.2% |
6.6 Dose Dependency of Side Effects in Clinical Trials
| Dose Groups | Placebo | Risperidone 2 mg |
Risperidone 6 mg |
Risperidone 10 mg |
Risperidone 16 mg |
|---|---|---|---|---|---|
| Parkinsonism | 1.2 |
0.9 |
1.8 |
2.4 |
2.6 |
| EPS Incidence | 13% |
17% |
21% |
21% |
35% |
| Dose Groups | Risperidone 1 mg |
Risperidone 4 mg |
Risperidone 8 mg |
Risperidone 12 mg |
Risperidone 16 mg |
|---|---|---|---|---|---|
| Parkinsonism |
0.6 |
1.7 |
2.4 |
2.9 |
4.1 |
| EPS Incidence |
7% |
12% |
17% |
18% |
20% |
Class Effect:
6.7 Changes in Body Weight
[see Use in Specific Populations (8.4)]
6.8 Changes in ECG
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia or bipolar mania. Information regarding changes in ECG during the treatment of pediatric patients with schizophrenia, 13 to 17 years of age and the treatment of pediatric patients with bipolar mania, 10 to 17 years of age is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
6.9 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Centrally-Acting Drugs and Alcohol
7.2 Drugs with Hypotensive Effects
7.3 Levodopa and Dopamine Agonists
7.4 Amitriptyline
7.5 Cimetidine and Ranitidine
7.6 Clozapine
7.7 Lithium
max
7.8 Valproate
max
7.9 Digoxin
7.10 Drugs That Inhibit CYP 2D6 and Other CYP Isozymes
[see Clinical Pharmacology (12.3)]
In vitro
7.11 Carbamazepine and Other Enzyme Inducers
7.12 Drugs Metabolized by CYP 2D6
In vitro
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
2222
22
in utero
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
[see Indications and Usage (1.3) Adverse Reactions (6.3) and Clinical Studies (14.4)]
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia or bipolar mania. Information on clinical trials and risperidone use for pediatric patients with schizophrenia, 13 to 17 years of age and the bipolar mania, 10 to 17 years of age is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
[see also Warnings and Precautions (5.4)]
[See also Adverse Reactions (6.7)]
[See also Adverse Reactions (6.1, 6.2, 6.3)] [see Dosage and Administration (2.1, 2.2, 2.3)]
[see Warnings and Precautions (5.6)]
8.5 Geriatric Use
[see Clinical Pharmacology (12.3) and Dosage and Administration (2.4, 2.5)][see Warnings and Precautions (5.7)]
[see Dosage and Administration (2.4)]
[See Boxed Warning and Warnings and Precautions (5.1)]
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
10 OVERDOSAGE
10.1 Human Experience
10.2 Management of Overdosage
11 DESCRIPTION
232742
N
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
22
221211C1D1A1-512
12.2 Pharmacodynamics
[see Clinical Pharmacology (12.3)]22 [see Clinical Pharmacology (12.1)]
12.3 Pharmacokinetics
Absorption
Food Effect
Distribution
1
Metabolism and Drug Interactions
N
[see Drug Interactions (7.12)]
[see Drug Interactions (7.11)][see Drug Interactions (7.12)]Excretion
14
Renal Impairment
[see Dosage and Administration (2.4) and Warnings and Precautions (5.17)]
Hepatic Impairment
1[see Dosage and Administration (2.4) and Warnings and Precautions (5.17)]
Elderly
[see Dosage and Administration (2.4)]
Pediatric
Race and Gender Effects
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
22
| Multiples of Maximum Human Dose in mg/m2 (mg/kg) |
||||
|---|---|---|---|---|
| Tumor Type | Species | Sex | 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 (37.5) |
1.5 (9.4) |
|
| Mammary gland neoplasm, Total |
rat |
male |
1.5 (9.4) |
0.4 (2.4) |
Mutagenesis
in vitroin vivoDrosophila
Impairment of Fertility
22
14 CLINICAL STUDIES
14.1 Schizophrenia
- In a 6-week, placebo-controlled trial (n=160) involving titration of risperidone in doses up to 10 mg/day (twice-daily schedule), risperidone was generally superior to placebo on the BPRS total score, on the BPRS psychosis cluster, and marginally superior to placebo on the SANS.
- In an 8-week, placebo-controlled trial (n=513) involving 4 fixed doses of risperidone (2 mg/day, 6 mg/day, 10 mg/day, and 16 mg/day, on a twice-daily schedule), all 4 risperidone groups were generally superior to placebo on the BPRS total score, BPRS psychosis cluster, and CGI severity score; the 3 highest risperidone dose groups were generally superior to placebo on the PANSS negative subscale. The most consistently positive responses on all measures were seen for the 6 mg dose group, and there was no suggestion of increased benefit from larger doses.
- In an 8-week, dose comparison trial (n=1356) involving 5 fixed doses of risperidone (1 mg/day, 4 mg/day, 8 mg/day, 12 mg/day, and 16 mg/day, on a twice-daily schedule), the four highest risperidone dose groups were generally superior to the 1 mg risperidone dose group on BPRS total score, BPRS psychosis cluster, and CGI severity score. None of the dose groups were superior to the 1 mg group on the PANSS negative subscale. The most consistently positive responses were seen for the 4 mg dose group.
- In a 4-week, placebo-controlled dose comparison trial (n=246) involving 2 fixed doses of risperidone (4 and 8 mg/day on a once-daily schedule), both risperidone dose groups were generally superior to placebo on several PANSS measures, including a response measure (>20% reduction in PANSS total score), PANSS and the BPRS psychosis cluster (derived from PANSS). The results were generally stronger for the 8 mg than for the 4 mg dose group.
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with schizophrenia. Clinical trial information for pediatric patients with schizophrenia, 13 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
14.2 Bipolar Mania – Monotherapy
- In one 3-week placebo-controlled trial (n=246), limited to patients with manic episodes, which involved a dose range of risperidone 1 to 6 mg/day, once daily, starting at 3 mg/day (mean modal dose was 4.1 mg/day), risperidone was superior to placebo in the reduction of YMRS total score.
- In another 3-week placebo-controlled trial (n=286), which involved a dose range of 1 to 6 mg/day, once daily, starting at 3 mg/day (mean modal dose was 5.6 mg/day), risperidone was superior to placebo in the reduction of YMRS total score.
Due to Janssen Pharmaceuticals Corporation’s marketing exclusivity rights, this drug product is not labeled for use in pediatric patients with bipolar mania. Clinical trial information for pediatric patients with bipolar mania, 10 to 17 years of age, is approved for Janssen Pharmaceuticals Corporation’s risperidone drug products.
14.3 Bipolar Mania – Combination Therapy
- In this 3-week placebo-controlled combination trial, 148 in- or outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms were randomized to receive risperidone, placebo, or an active comparator, in combination with their original therapy. Risperidone, in a dose range of 1 to 6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.8 mg/day), combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1.4 mEq/L or 50 mcg/mL to 120 mcg/mL, respectively) was superior to lithium or valproate alone in the reduction of YMRS total score.
- In a second 3-week placebo-controlled combination trial, 142 in- or outpatients on lithium, valproate, or carbamazepine therapy with inadequately controlled manic or mixed symptoms were randomized to receive risperidone or placebo, in combination with their original therapy. Risperidone, in a dose range of 1 to 6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.7 mg/day), combined with lithium, valproate, or carbamazepine (in therapeutic ranges of 0.6 mEq/L to 1.4 mEq/L for lithium, 50 mcg/mL to 125 mcg/mL for valproate, or 4 to 12 mcg/mL for carbamazepine, respectively) was not superior to lithium, valproate, or carbamazepine alone in the reduction of YMRS total score. A possible explanation for the failure of this trial was induction of risperidone and 9-hydroxyrisperidone clearance by carbamazepine, leading to subtherapeutic levels of risperidone and 9-hydroxyrisperidone.
14.4 Irritability Associated with Autistic Disorder
- In one of the 8-week, placebo-controlled trials, children and adolescents with autistic disorder (n=101), aged 5 to 16 years, received twice daily doses of placebo or risperidone 0.5 to 3.5 mg/day on a weight-adjusted basis. Risperidone, starting at 0.25 mg/day or 0.5 mg/day depending on baseline weight (< 20 kg and ≥ 20 kg, respectively) and titrated to clinical response (mean modal dose of 1.9 mg/day, equivalent to 0.06 mg/kg/day), significantly improved scores on the ABC-I subscale and on the CGI-C scale compared with placebo.
- In the other 8-week, placebo-controlled trial in children with autistic disorder (n=55), aged 5 to 12 years, risperidone 0.02 to 0.06 mg/kg/day given once or twice daily, starting at 0.01 mg/kg/day and titrated to clinical response (mean modal dose of 0.05 mg/kg/day, equivalent to 1.4 mg/day), significantly improved scores on the ABC-I subscale compared with placebo.
16 HOW SUPPLIED/STORAGE AND HANDLING
Risperidone Tablets USP, 0.25 mg
Risperidone Tablets USP, 0.5 mg
Risperidone Tablets USP, 1 mg
Risperidone Tablets USP, 2 mg
Risperidone Tablets USP, 3 mg
Risperidone Tablets USP, 4 mg
Storage and Handling
Store at
17 PATIENT COUNSELING INFORMATION
17.1 Orthostatic Hypotension
[see Warnings and Precautions (5.7)]
17.2 Interference with Cognitive and Motor Performance
[see Warnings and Precautions (5.9)]
17.3 Pregnancy
[see Use in Specific Populations (8.1)]
17.4 Nursing
[see Use in Specific Populations (8.3)]
17.5 Concomitant Medication
[see Drug Interactions (7)]
17.6 Alcohol
[see Drug Interactions (7.1)]
Aurolife Pharma LLC
Gen-Source Rx
620 Gotham Parkway
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 0.25 mg (500 Tablet Bottle)
NDC 52343-003-05
Risperidone Tablets, USP
0.25 mg
Rx only 500 Tablets
GEN-SOURCE
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 0.5 mg (500 Tablet Bottle)
NDC 52343-004-05
Risperidone Tablets, USP
0.5 mg
Rx only 500 Tablets
GEN-SOURCE
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 1 mg (500 Tablet Bottle)
NDC 52343-005-05
Risperidone Tablets, USP
1 mg
Rx only 500 Tablets
GEN-SOURCE
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 2 mg (500 Tablet Bottle)
NDC 52343-006-05
Risperidone Tablets, USP
2 mg
Rx only 500 Tablets
GEN-SOURCE
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 3 mg (500 Tablet Bottle)
NDC 52343-007-05
Risperidone Tablets, USP
3 mg
Rx only 500 Tablets
GEN-SOURCE
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg (60 Tablet Bottle)
NDC 52343-008-60
Risperidone Tablets, USP
4 mg
Rx only 60 Tablets
GEN-SOURCE
RisperidoneRisperidone TABLET, FILM COATED
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RisperidoneRisperidone TABLET, FILM COATED
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PLEASE, BE CAREFUL!
Be sure to consult your doctor before taking any medication!
