HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use RISPERDAL ® safely and effectively. See full prescribing information for RISPERDAL ®.
RISPERDAL ® (risperidone) tablets, RISPERDAL® (risperidone) oral solution, RISPERDAL ® M-TAB ® (risperidone) orally disintegrating tablets
Initial U.S. Approval: 1993
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. RISPERDAL® is not approved for use in patients with dementia-related psychosis. (5.1)
RECENT MAJOR CHANGES
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Warnings and Precautions, Leukopenia, Neutropenia, and Agranulocytosis (5.8) |
07/2009 |
INDICATIONS AND USAGE
RISPERDAL® is an atypical antipsychotic agent indicated for:
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Treatment of schizophrenia in adults and adolescents aged 13–17 years (1.1)
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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, and alone in children and adolescents aged 10–17 years (1.2)
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Treatment of irritability associated with autistic disorder in children and adolescents aged 5–16 years (1.3)
DOSAGE AND ADMINISTRATION
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Initial Dose |
Titration |
Target Dose |
Effective Dose Range |
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Schizophrenia- adults (2.1) |
2 mg/day |
1–2 mg daily |
4–8 mg daily |
4–16 mg/day |
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Schizophrenia – adolescents (2.1) |
0.5mg/day |
0.5– 1 mg daily |
3mg/day |
1–6 mg/day |
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Bipolar mania – adults (2.2) |
2–3 mg/day |
1mg daily |
1–6mg/day |
1–6 mg/day |
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Bipolar mania in children/adolescents (2.2) |
0.5 mg/day |
0.5–1mg daily |
2.5mg/day |
0.5–6 mg/day |
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Irritability associated with autistic disorder (2.3) |
0.25 mg/day (<20 kg)
0.5 mg/day (≥20 kg) |
0.25–0.5 mg at ≥ 2 weeks |
0.5 mg/day (<20 kg)
1 mg/day (≥20 kg) |
0.5–3 mg/day |
DOSAGE FORMS AND STRENGTHS
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Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg (3)
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Oral solution: 1 mg/mL (3)
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Orally disintegrating tablets: 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg (3)
CONTRAINDICATIONS
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Known hypersensitivity to the product (4)
WARNINGS AND PRECAUTIONS
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Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis. RISPERDAL® is not approved for use in patients with dementia-related psychosis (5.2)
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Neuroleptic Malignant Syndrome (5.3)
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Tardive dyskinesia (5.4)
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Hyperglycemia and diabetes mellitus (5.5)
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Hyperprolactinemia (5.6)
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Orthostatic hypotension (5.7)
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Leukopenia, Neutropenia, and Agranulocytosis: has been reported with antipsychotics, including risperidone. Patients with a history of a clinically significant low white blood cell count (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. (5.8)
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Potential for cognitive and motor impairment (5.9)
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Seizures (5.10)
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Dysphagia (5.11)
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Priapism (5.12)
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Thrombotic Thrombocytopenic Purpura (TTP) (5.13)
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Disruption of body temperature regulation (5.14)
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Antiemetic Effect (5.15)
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Suicide (5.16)
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Increased sensitivity in patients with Parkinson's disease or those with dementia with Lewy bodies (5.17)
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Diseases or conditions that could affect metabolism or hemodynamic responses (5.17)
ADVERSE REACTIONS
The most common adverse reactions in clinical trials (≥10%) were somnolence, appetite increased, fatigue, rhinitis, upper respiratory tract infection, vomiting, coughing, urinary incontinence, saliva increased, constipation, fever, Parkinsonism, dystonia, abdominal pain, anxiety, nausea, dizziness, dry mouth, tremor, rash, akathisia, and dyspepsia. (6)
The most common adverse reactions that were associated with discontinuation from clinical trials were somnolence, nausea, abdominal pain, dizziness, vomiting, agitation, and akathisia. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Janssen, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
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Due to CNS effects, use caution when administering with other centrally-acting drugs. Avoid alcohol. (7.1)
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Due to hypotensive effects, hypotensive effects of other drugs with this potential may be enhanced. (7.2)
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Effects of levodopa and dopamine agonists may be antagonized. (7.3)
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Cimetidine and ranitidine increase the bioavailability of risperidone. (7.5)
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Clozapine may decrease clearance of risperidone. (7.6)
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Fluoxetine and paroxetine increase plasma concentrations of risperidone. (7.10)
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Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (7.11)
USE IN SPECIFIC POPULATIONS
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Nursing Mothers: should not breast feed. (8.3)
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Pediatric Use: safety and effectiveness not established for schizophrenia less than 13 years of age, for bipolar mania less than 10 years of age, and for autistic disorder less than 5 years of age. (8.4)
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Elderly or debilitated; severe renal or hepatic impairment; predisposition to hypotension or for whom hypotension poses a risk: Lower initial dose (0.5 mg twice daily), followed by increases in dose in increments of no more than 0.5 mg twice daily. Increases to dosages above 1.5 mg twice daily should occur at intervals of at least 1 week. (8.5, 2.4)
See 17 for PATIENT COUNSELING INFORMATION, Medication Guide and Medication Guide.
Revised: 12/2010
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Schizophrenia
Adults
RISPERDAL® (risperidone) is indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1)].
Adolescents
RISPERDAL® is indicated for the treatment of schizophrenia in adolescents aged 13–17 years [see Clinical Studies (14.1)].
1.2 Bipolar Mania
Monotherapy - Adults and Pediatrics
RISPERDAL® is indicated for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder in adults and in children and adolescents aged 10–17 years [see Clinical Studies (14.2)].
Combination Therapy – Adults
The combination of RISPERDAL® with lithium or valproate is indicated for the short-term treatment of acute manic or mixed episodes associated with Bipolar I Disorder [see Clinical Studies (14.3)].
1.3 Irritability Associated with Autistic Disorder
Pediatrics
RISPERDAL® is indicated for the treatment of irritability associated with autistic disorder in children and adolescents aged 5–16 years, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods [see Clinical Studies (14.4)].
2 DOSAGE AND ADMINISTRATION
2.1 Schizophrenia
Adults
Usual Initial Dose
RISPERDAL® can be administered once or twice daily. Initial dosing is generally 2 mg/day. Dose increases should then occur at intervals not less than 24 hours, in increments of 1–2 mg/day, as tolerated, to a recommended dose of 4–8 mg/day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4–16 mg/day [see Clinical Studies (14.1)]. However, doses above 6 mg/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/day has not been eva luated in clinical trials.
Maintenance Therapy
While it is unknown how long a patient with schizophrenia should remain on RISPERDAL®, the effectiveness of RISPERDAL® 2 mg/day to 8 mg/day at delaying relapse was demonstrated in a controlled trial in patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Patients should be periodically reassessed to determine the need for maintenance treatment with an appropriate dose.
Adolescents
The dosage of RISPERDAL® should be initiated at 0.5 mg once daily, administered as a single-daily dose in either the morning or evening. Dosage adjustments, if indicated, should occur at intervals not less than 24 hours, in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 3 mg/day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 and 6 mg/day, no additional benefit was seen above 3 mg/day, and higher doses were associated with more adverse events. Doses higher than 6 mg/day have not been studied.
Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.
There are no controlled data to support the longer term use of RISPERDAL® beyond 8 weeks in adolescents with schizophrenia. The physician who elects to use RISPERDAL® for extended periods in adolescents with schizophrenia should periodically re-eva luate the long-term usefulness of the drug for the individual patient.
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. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some schizophrenic patients, more gradual discontinuation may be most appropriate for others. The period of overlapping antipsychotic administration should be minimized. When switching schizophrenic patients from depot antipsychotics, initiate RISPERDAL® therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-eva luated periodically.
2.2 Bipolar Mania
Usual Dose
Adults
RISPERDAL® should be administered on a once-daily schedule, starting with 2 mg to 3 mg per day. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments/decrements of 1 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 1–6 mg per day [see Clinical Studies (14.2, 14.3)]. RISPERDAL® doses higher than 6 mg per day were not studied.
Pediatrics
The dosage of RISPERDAL® should be initiated at 0.5 mg once daily, administered as a single-daily dose in either the morning or evening. Dosage adjustments, if indicated, should occur at intervals not less than 24 hours, in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dose of 2.5 mg/day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 and 6 mg/day, no additional benefit was seen above 2.5 mg/day, and higher doses were associated with more adverse events. Doses higher than 6 mg/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-eva luate the long-term risks and benefits of the drug for the individual patient.
2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)
The safety and effectiveness of RISPERDAL® in pediatric patients with autistic disorder less than 5 years of age have not been established.
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.
Dosing should be initiated at 0.25 mg per day for patients < 20 kg and 0.5 mg per day for patients ≥ 20 kg. After a minimum of four days from treatment initiation, the dose may be increased to the recommended dose of 0.5 mg per day for patients < 20 kg and 1 mg per day for patients ≥ 20 kg. This dose should be maintained for a minimum of 14 days. In patients not achieving sufficient clinical response, dose increases may be considered at ≥ 2-week intervals in increments of 0.25 mg per day for patients < 20 kg or 0.5 mg per day for patients ≥ 20 kg. Caution should be exercised with dosage for smaller children who weigh less than 15 kg.
In clinical trials, 90% of patients who showed a response (based on at least |
