Kenyan Health Patient Information Leaflet
Atypical Antipsychotic [EPC]
1 INDICATIONS AND USAGE Risperidone tablets are an atypical antipsychotic indicated for: Treatment of schizophrenia ( 1.1 ) As monotherapy or adjunctive therapy with lithium or valproate, for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder ( 1.2 ) Treatment of irritability associated with autistic disorder ( 1.3 ) 1.1 Schizophrenia Risperidone tablets are 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 [see Clinical Studies (14.1) ] . 1.2 Bipolar Mania Monotherapy Risperidone tablets are 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) [see Clinical Studies (14.2) ] . Adjunctive Therapy Risperidone tablets 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 [see Clinical Studies (14.3) ] . 1.3 Irritability Associated with Autistic Disorder Risperidone tablets are 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) [see Clinical Studies (14.4) ] .
1. Recommended Daily Dosage by Indication Initial Dose Titration (Increments) Target Dose Effective Dose Range Schizophrenia: adults ( 2.1 ) 2 mg 1 to 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents ( 2.2 ) 0.5 mg 0.5 to 1 mg 3 mg 1 to 6 mg Bipolar mania: adults ( 2.2 ) 2 to 3 mg 1 mg 1 to 6 mg 1 to 6 mg Bipolar mania: children and adolescents ( 2.2 ) 0.5 mg 0.5 to 1 mg 1 to 2.5 mg 1 to 6 mg Irritability in autistic disorder ( 2.3 ) 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. Recommended daily dosage: Initial Dose Target Dose Effective Dose Range Schizophrenia: adults ( 2.1 ) 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents ( 2.1 ) 0.5 mg 3 mg 1 to 6 mg Bipolar mania: Adults ( 2.2 ) 2 to 3 mg 1 to 6 mg 1 to 6 mg Bipolar mania: in children and adolescents ( 2.2 ) 0.5 mg 1 to 2.5 mg 1 to 6 mg Irritability associated with autistic disorder ( 2.3 ) 0.25 mg (Weight < 20 kg) 0.5 mg (Weight ≥20 kg) 0.5 mg (<20 kg) 1 mg (≥20 kg) 0.5 to 3 mg Severe Renal or 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 at least one week. ( 2.4 ) 2.1 Schizophrenia Adults Usual Initial Dose Risperidone tablets 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 [see Clinical Studies (14.1) ]. 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 and 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 risperidone tablets, the effectiveness of risperidone tablets 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 [see Clinical Studies (14.1) ] . 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 risperidone tablets, 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 risperidone tablets, or treating patients with concomitant antipsychotics. 2.2 Bipolar Mania Usual Dose Adults The inital 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 [see Clinical Studies (14.2 , 14.3) ] . Risperidone tablets doses higher than 6 mg per day were not studied. Pediatrics The inital 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 risperidone tablets. 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 risperidone tablets in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone tablets for extended periods should periodically re-evaluate 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 dosage of risperidone tablets should be individualized according to the response and tolerability of the patient. The total daily dose of risperidone tablets 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 risperidone tablets 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. 2.4 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 [see Use in Specific Populations (8.6 and 8.7) ] . 2.5 Dose Adjustments for Specific Drug Interactions When risperidone tablets are co-administered with enzyme inducers (e.g., carbamazepine), the dose of risperidone tablets should be increased up to double the patient’s usual dose. It may be necessary to decrease the risperidone tablets dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1) ] . Similar effect may be expected with co-administration of risperidone tablets with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital). When fluoxetine or paroxetine is co-administered with risperidone tablets, the dose of risperidone tablets should be reduced. The risperidone tablets dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, risperidone tablets should be titrated slowly. It may be necessary to increase the risperidone tablets dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1) ] .
labeling: • Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions ( 5.2 )] • Neuroleptic malignant syndrome [see Warnings and Precautions ( 5.3 )] • Tardive dyskinesia [see Warnings and Precautions ( 5.4 )] • Metabolic Changes (Hyperglycemia and diabetes mellitus, Dyslipidemia, and Weight Gain) [see Warnings and Precautions ( 5.5 )] • Hyperprolactinemia [see Warnings and Precautions ( 5.6 )] • Orthostatic hypotension [see Warnings and Precautions ( 5.7 )] • Falls [see Warnings and Precautions ( 5.8 )] • Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions ( 5.9 )] • Potential for cognitive and motor impairment [see Warnings and Precautions ( 5.10 )] • Seizures [see Warnings and Precautions ( 5.11 )] • Dysphagia [see Warnings and Precautions ( 5.12 )] • Priapism [see Warnings and Precautions ( 5.13 )] • Disruption of body temperature regulation [see Warnings and Precautions ( 5.14 )] 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 [see Adverse Reactions, Discontinuations Due to Adverse Reactions ( 6.1 )] . 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 risperidone tablets 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 risperidone tablets while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with risperidone tablets 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. 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. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ajanta Pharma USA Inc. at 855-664-7744 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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 risperidone tablets-treated adult patients with schizophrenia in three 4- to 8-week, double-blind, placebo-controlled trials. Table 8. Adverse Reactions in ≥2% of Risperidone Tablets-Treated Adult Patients (and greater than placebo) with Schizophrenia in Double-Blind, Placebo-Controlled Trials * 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. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets 2–8 mg per day (N=366) >8–16 mg per day (N=198) Placebo (N=225) 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 Pediatric Patients with Schizophrenia Table 9 lists the adverse reactions reported in 5% or more of risperidone tablets-treated pediatric patients with schizophrenia in a 6-week double-blind, placebo-controlled trial. Table 9. Adverse Reactions in ≥5% of Risperidone Tablets-Treated Pediatric Patients (and greater than placebo) with Schizophrenia in a Double-Blind Trial * Parkinsonism includes extrapyramidal disorder, muscle rigidity, musculoskeletal stiffness, and hypokinesia. Akathisia includes akathisia and restlessness. Dystonia includes dystonia and oculogyration. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets 1–3 mg per day (N=55) 4–6 mg per day (N=51) Placebo (N=54) 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 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 risperidone tablets-treated adult patients with bipolar mania in four 3-week, double-blind, placebo-controlled monotherapy trials. Table 10. Adverse Reactions in ≥2% of Risperidone Tablets-Treated Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Monotherapy Trials * 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. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets 1–6 mg per day (N=448) Placebo (N=424) 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 Table 11 lists the adverse reactions reported in 2% or more of risperidone tablets-treated adult patients with bipolar mania in two 3-week, double-blind, placebo-controlled adjuvant therapy trials. Table 11. Adverse Reactions in ≥2% of Risperidone Tablets-Treated Adult Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Adjunctive Therapy Trials * Parkinsonism includes extrapyramidal disorder, hypokinesia and bradykinesia. Akathisia includes hyperkinesia and akathisia. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets + 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 Pediatric Patients with Bipolar Mania Table 12 lists the adverse reactions reported in 5% or more of risperidone tablets-treated pediatric patients with bipolar mania in a 3-week double-blind, placebo-controlled trial. Table 12. Adverse Reactions in ≥5% of Risperidone Tablets-Treated Pediatric Patients (and greater than placebo) with Bipolar Mania in Double-Blind, Placebo-Controlled Trials * Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, bradykinesia, and nuchal rigidity. Dystonia includes dystonia, laryngospasm, and muscle spasms. Akathisia includes restlessness and akathisia. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets 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 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 risperidone tablets-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 Risperidone Tablets-Treated Pediatric Patients (and greater than placebo) Treated for Irritability Associated with Autistic Disorder in Double-Blind, Placebo-Controlled Trials * Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, muscle rigidity, cogwheel rigidity, and muscle tightness. System/Organ Class Adverse Reaction Percentage of Patients Reporting Reaction Risperidone Tablets 0.5–4.0 mg per 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…
16 HOW SUPPLIED/STORAGE AND HANDLING Risperidone Tablets, USP 1 mg are white to off white, circular, biconvex, film-coated tablets, engraved with 'RI3' on one side and plain on other and are supplied as follows: NDC: 70518-0364-00 NDC: 70518-0364-01 NDC: 70518-0364-02 NDC: 70518-0364-03 NDC: 70518-0364-04 PACKAGING: 30 in 1 BLISTER PACK PACKAGING: 30 in 1 BLISTER PACK PACKAGING: 30 in 1 BOTTLE PLASTIC PACKAGING: 50 in 1 BOX PACKAGING: 1 in 1 POUCH Risperidone tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. Protect from light and moisture. Keep out of reach of children. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762