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RISPERIDONE is a brand name for Risperidone. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Table 1. 5 mg twice daily. 5 mg twice daily at intervals of one week or longer. 5 mg twice daily. 5 mg twice daily at intervals of at least one week. 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. 1) ]. 5 mg once daily, administered as a single-daily dose in the morning or evening. 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. 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 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.
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.
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. 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.
2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of risperidone tablets and close monitoring. 3 ) Tardive dyskinesia: Consider discontinuing risperidone tablets if clinically indicated. 4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular / cerebrovascular risk.
These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. 5 ) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes.
5 ) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. 5 ) Weight Gain : Significant weight gain has been reported. Monitor weight gain. 5 ) Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration.
6 ) Orthostatic hypotension: For patients at risk, consider a lower starting dose and slower titration. 7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts in patients with a history of clinically significant low white blood cell count (WBC).
Consider discontinuing risperidone tablets if a clinically significant decline in WBC occurs in the absence of other causative factors. 9 ) Potential for cognitive and motor impairment: Use caution when operating machinery. 10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
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. 7 times the risk of death in placebo-treated patients.
6% in the placebo group. , 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.
4 CONTRAINDICATIONS Risperidone tablets are contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the risperidone tablets 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. Known hypersensitivity to risperidone, paliperidone, or to any excipients in risperidone tablets. ( 4 )
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3) ] . Risperidone tablets doses higher than 6 mg per day were not studied. 5 mg once daily, administered as a single-daily dose in the morning or evening. 5 mg per day. 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.
, 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. 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. 25 mg per day. 5 mg per day. 0 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days.
5 mg per day for patients greater than or equal to 20 kg. 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.
5 mg twice daily. 5 mg or less, administered twice daily. 7) ] . , carbamazepine), the dose of risperidone tablets should be increased up to double the patient’s usual dose. 1) ] . , 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. 1) ] .
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. 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.
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 1 Renal and Urinary Disorders Enuresis 16 10 Respiratory, Thoracic and Mediastinal Disorders Cough 17 12 Rhinorrhea 12 10 Nasal congestion 10 4 Skin and Subcutaneous Tissue Disorders Rash 8 5 Other Adverse Reactions Observed During the Clinical Trial Evaluation of Risperidone The following additional adverse reactions occurred across all placebo-controlled, active-controlled, and open-label studies of risperidone tablets 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 Discontinuations Due to Adverse Reactions Schizophrenia - Adults Approximately 7% (39/564) of risperidone tablets-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 risperidone tablets-treated patients were: Table 14. 4% in active control-treated patients in a double-blind, placebo- and active-controlled trial. Schizophrenia – Pediatrics Approximately 7% (7/106), of risperidone tablets-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 risperidone tablets-treated patient were dizziness (2%), somnolence (1%), sedation (1%), lethargy (1%), anxiety (1%), balance disorder (1%), hypotension (1%), and palpitation (1%).
Bipolar Mania – Adults In double-blind, placebo-controlled trials with risperidone tablets as monotherapy, approximately 6% (25/448) of risperidone tablets-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 risperidone tablets-treated patients were: Table 15. 2% Bipolar Mania – Pediatrics In a double-blind, placebo-controlled trial 12% (13/111) of risperidone tablets-treated patients discontinued due to an adverse reaction, compared with 7% (4/58) of placebo-treated patients.
The adverse reactions associated with discontinuation in more than one risperidone tablets-treated pediatric patient were nausea (3%), somnolence (2%), sedation (2%), and vomiting (2%). Autistic Disorder – Pediatrics In the two 8-week, placebo-controlled trials in pediatric patients treated for irritability associated with autistic disorder (n = 156), one risperidone tablets-treated patient discontinued due to an adverse reaction (Parkinsonism), and one placebo-treated patient discontinued due to an adverse event.
Dose Dependency of Adverse Reactions in Clinical Trials Extrapyramidal Symptoms Data from two fixed-dose trials in adults with schizophrenia provided evidence of dose-relatedness for extrapyramidal symptoms associated with risperidone tablets treatment.
Two methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 4 fixed doses of risperidone tablets (2, 6, 10, and 16 mg/day), including (1) a Parkinsonism score (mean change from baseline) from the Extrapyramidal Symptom Rating Scale, and (2) incidence of spontaneous complaints of EPS: Table 16.
6 EPS Incidence 13% 17% 21% 21% 35% Similar methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 5 fixed doses of risperidone tablets (1, 4, 8, 12, and 16 mg/day): Table 17. 1 EPS Incidence 7% 12% 17% 18% 20% Dystonia Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment.
Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs.
An elevated risk of acute dystonia is observed in males and younger age groups. Other Adverse Reactions Adverse event data elicited by a checklist for side effects from a large study comparing 5 fixed doses of risperidone tablets (1, 4, 8, 12, and 16 mg/day) were explored for dose-relatedness of adverse events.
05) for the following adverse reactions: somnolence, vision abnormal, dizziness, palpitations, weight increase, erectile dysfunction, ejaculation disorder, sexual function abnormal, fatigue, and skin discoloration. 4) ]. Changes in ECG Parameters Between-group comparisons for pooled placebo-controlled trials in adults revealed no statistically significant differences between risperidone and placebo in mean changes from baseline in ECG parameters, including QT, QTc, and PR intervals, and heart rate.
When all risperidone tablets doses were pooled from randomized controlled trials in several indications, there was a mean increase in heart rate of 1 beat per minute compared to no change for placebo patients. In short-term schizophrenia trials, higher doses of risperidone (8-16 mg/day) were associated with a higher mean increase in heart rate compared to placebo (4-6 beats per minute).
In pooled placebo-controlled acute mania trials in adults, there were small decreases in mean heart rate, similar among all treatment groups. 5 beats per minute in the placebo group. There were no other notable ECG changes. In a placebo-controlled acute mania trial in children and adolescents (aged 10 – 17 years), there were no significant changes in ECG parameters, other than the effect of risperidone tablets to transiently increase pulse rate (< 6 beats per minute).
In two controlled schizophrenia trials in adolescents (aged 13 – 17 years), there were no clinically meaningful changes in ECG parameters including corrected QT intervals between treatment groups or within treatment groups over time.
2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of risperidone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These adverse reactions include: alopecia, anaphylactic reaction, angioedema, atrial fibrillation, cardiopulmonary arrest, catatonia, diabetic ketoacidosis in patients with impaired glucose metabolism, dysgeusia, hypoglycemia, hypothermia, ileus, inappropriate antidiuretic hormone secretion, intestinal obstruction, jaundice, mania, pancreatitis, pituitary adenoma, precocious puberty, pulmonary embolism, QT prolongation, sleep apnea syndrome, somnambulism, Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), sudden death, thrombocytopenia, thrombotic thrombocytopenic purpura, urinary retention, and water intoxication.
Postmarketing cases of extrapyramidal symptoms (dystonia and dyskinesia) have been reported in patients concomitantly taking methylphenidate and risperidone when there was an increase or decrease in dosage, initiation, or discontinuation of either or both medications.
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 risperidone tablets when compared to patients treated with risperidone tablets 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. Risperidone tablets are not approved for the treatment of dementia-related psychosis [see Boxed Warning ] .
, 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.
Risperidone tablets are not approved for the treatment of patients with dementia-related psychosis. 1) ] . 3 Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with antipsychotic drugs.
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
If NMS is suspected, immediately discontinue risperidone tablets and provide symptomatic treatment and monitoring. 4 Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs.
Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible increase with the duration of treatment and the cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low doses.
It may also occur after discontinuation of treatment. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process.
The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, risperidone tablets should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia.
Chronic antipsychotic treatment should generally be reserved for patients: (1) who suffer from a chronic illness that 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, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment. If signs and symptoms of tardive dyskinesia appear in a patient on risperidone tablets, drug discontinuation should be considered.
However, some patients may require treatment with risperidone tablets despite the presence of the syndrome. 5 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 risperidone tablets.
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 risperidone tablets, should be monitored regularly for worsening of glucose control.
, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics, including risperidone tablets, should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
Any patient treated with atypical antipsychotics, including risperidone tablets, 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 risperidone tablets, should undergo fasting blood glucose testing.
In some cases, hyperglycemia has resolved when the atypical antipsychotic, including risperidone tablets, was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of risperidone tablets.
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. 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. 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. 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. 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. 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. 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. 0 kg was observed after 8 months of risperidone tablets 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. 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 risperidone tablets. 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.
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 risperidone tablets for any indication, weight gain should be assessed against that expected with normal growth.
6 Hyperprolactinemia As with other drugs that antagonize dopamine D2 receptors, risperidone tablets elevates prolactin levels and the elevation persists during chronic administration. Risperidone tablets are 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. Tissuecultureexperiments 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.
1 )]. Published epidemiologic studies have shown inconsistent results when exploring the potential association between hyperprolactinemia and breast cancer. 7 Orthostatic Hypotension Risperidone tablets 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.
2% (6/2607) of risperidone tablets-treated patients in Phase 2 and 3 studies in adults with schizophrenia. 4 )] . 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.
, dehydration and hypovolemia, and in the elderly and patients with renal or hepatic impairment. Monitoring of orthostatic vital signs should be considered if hypotension occurs. Clinically significant hypotension has been observed with concomitant use of risperidone tablets and antihypertensive medication.
8 Falls Somnolence, postural hypotension, motor and sensory instability have been reported with the use of antipsychotics, including risperidone tablets, which may lead to falls and, consequently, fractures or other fall-related injuries.
For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
9 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 risperidone tablets.
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 risperidone tablets 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/mm 3 ) should discontinue risperidone tablets and have their WBC followed until recovery.
10 Potential for Cognitive and Motor Impairment Somnolence was a commonly reported adverse reactions associated with risperidone tablets 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 (risperidone tablets 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 risperidone tablets 16 mg/day patients and 1% of placebo patients reported somnolence as an adverse reation. Since risperidone tablets have 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 risperidone tablets therapy does not affect them adversely.
3% (9/2607) of risperidone tablets-treated patients, two in association with hyponatremia. Risperidone tablets should be used cautiously in patients with a history of seizures. 12 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. Risperidone tablets and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
1) ]. 13 Priapism Priapism has been reported during postmarketing surveillance. Severe priapism may require surgical intervention. 14 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 risperidone tablets use. Caution is advised when prescribing for patients who will be exposed to temperature extremes.