Risperidoneside effects

The following are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis Neuroleptic malignant syndrome Tardive dyskinesia Metabolic changes Hyperprolactinemia Orthostatic hypotension and syncope Falls Leukopenia, neutropenia and agranulocytosis Potential for cognitive and motor impairment Seizures Dysphagia Priapism Body temperature regulation The most common adverse reactions with risperidone in patients with schizophrenia (≥5% and greater than 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 with risperidone in patients with bipolar disorder were weight increased (5% in monotherapy trial) and tremor and parkinsonism (≥10% in adjunctive therapy trial). The most common injection site reactions with UZEDY in patients with schizophrenia (≥5% and greater than placebo) were pruritus and nodule. To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 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. Treatment of Schizophrenia in Adults UZEDY is to be administered subcutaneously. The safety of UZEDY for the treatment of schizophrenia in adults is based on adequate and well-controlled studies of oral risperidone in studies of patients with schizophrenia and other indications. The results of those adequate and well-controlled studies are presented below. The data described in this section are derived from a clinical trial database consisting of 9,803 patients exposed to one or more doses of oral risperidone for the treatment of schizophrenia and other psychiatric disorders. Of these 9,803 patients, 2,687 were patients who received oral risperidone while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with oral risperidone 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 reactions and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs. Injection site reactions for UZEDY presented in this section (see “Injection Site Reactions with UZEDY” below) are based on a randomized withdrawal study in patients with schizophrenia consisting of a 12-week open-label oral risperidone (2 mg to 5 mg) stabilization phase, followed by a placebo-controlled phase in which patients were randomized to UZEDY (once monthly or once every 2 months) or placebo for a variable time until impending relapse or study completion. The safety of UZEDY was evaluated in a total of 740 adult patients with schizophrenia who received at least 1 dose of UZEDY during the clinical development program. A total of 351 patients were exposed to UZEDY for at least 6 months, of which 221 patients were exposed to UZEDY for at least 12 months, which included 112 patients exposed to once monthly and 109 patients to once every 2 months dosing regimens. In addition, 32 patients were exposed to UZEDY for at least 24 months. Treatment of Bipolar Disorder in Adults UZEDY is to be administered subcutaneously. The data presented below are from studies with another risperidone long-acting injection given once every 2 weeks that was administered intramuscularly. The safety of UZEDY as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder in adults is based on adequate and well-controlled studies of another risperidone long-acting injection given once every 2 weeks. The results of those adequate and well-controlled studies are presented below. Safety data are presented from a trial assessing the efficacy and safety of another risperidone long-acting injection, given once every 2 weeks, when administered as monotherapy for maintenance treatment in patients with bipolar I disorder. Safety data are also presented from a trial assessing the efficacy and safety of another risperidone long-acting injection, given once every 2 weeks, administered as adjunctive maintenance treatment in patients with bipolar disorder. Adverse Reactions in Studies with Oral Risperidone The most common adverse reactions in clinical trials of oral risperidone (>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. Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Adult Patients with Schizophrenia Treated with Oral Risperidone Table 7 lists the adverse reactions reported in 2% or more of oral risperidone-treated adult patients with schizophrenia in three 4- to 8-week, double-blind, placebo-controlled trials.

Table 7: Adverse Reactions in ≥2% of Oral Risperidone-Treated Adult Patients (and greater than placebo) with Schizophrenia in Double-Blind, Placebo-Controlled Trials Percentage of Patients Reporting Reaction Oral Risperidone System/Organ Class Adverse Reaction 2 mg to 8 mg per day (N=366) >8 mg to 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 * 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. Adverse Reactions in Studies with Another Long-Acting Injection Risperidone, Given Once Every 2 Weeks The most common adverse reactions in the double-blind, placebo-controlled periods of the bipolar disorder trials of another risperidone long-acting injection were weight increased (5% in the monotherapy trial) and tremor and parkinsonism (≥ 10% in the adjunctive treatment trial). Commonly-Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials – Adult Patients with Bipolar Disorder Treated with Another Risperidone Long-Acting Injection Given Once Every 2 Weeks Table 8 lists the treatment-emergent adverse reactions reported in 2% or more of patients treated with another risperidone long-acting injection, given once every 2 weeks, in the 24-month double-blind, placebo-controlled treatment period of the trial assessing the efficacy and safety of another risperidone long-acting injection when administered as monotherapy for maintenance treatment in patients with bipolar I disorder.

Table 8: Adverse Reactions in ≥2% of Adult Patients with Bipolar I Disorder Treated with Another Risperidone Long-Acting Injection, Given Once Every 2 Weeks, as Monotherapy in a 24-Month Double-Blind, Placebo-Controlled Trial Percentage of Patients Reporting Event System/Organ Class Adverse Reaction Risperidone Long-Acting Injection a (N=154) Placebo (N=149) Investigations Weight increased 5 1 Nervous system disorders Dizziness 3 1 Vascular disorders Hypertension 3 1 a The data presented are from a study with another risperidone long-acting injection that was administered once every 2 weeks, intramuscularly. UZEDY is to be administered subcutaneously. Table 9 lists the treatment-emergent adverse reactions reported in 4% or more of patients in the 52-week double-blind, placebo-controlled treatment phase of a trial assessing the efficacy and safety of another Risperidone Long-Acting Injection, given once every 2 weeks, when administered as adjunctive maintenance treatment in patients with bipolar disorder.

Table 9: Adverse Reactions Occurring in ≥4% of Adult Patients with Bipolar I Disorder Treated with Another Risperidone Long-Acting Injection, Given Once Every 2 Weeks, as Adjunctive Therapy in a 52-Week Double-Blind, Placebo-Controlled Trial Percentage of Patients Reporting Event System/Organ Class Adverse Reaction Risperidone Long-Acting Injection a + Treatment as Usual b (N=72) Placebo + Treatment as Usual b (N=67) General disorders and administration site conditions Gait abnormal 4 0 Infections and infestations Upper respiratory tract infection 6 3 Investigations Weight increased 7 1 Metabolism and nutrition disorders Decreased appetite 6 1 Increased appetite 4 0 Musculoskeletal and connective tissue disorders Arthralgia 4 3 Nervous system disorders Tremor 24 16 Parkinsonism c 15 6 Dyskinesia d 6 3 Sedation e 7 1 Disturbance in attention 4 0 Reproductive system and breast disorders Amenorrhea 4 1 Respiratory, thoracic and mediastinal disorders Cough 4 1 a The data presented are from a study with another risperidone long-acting injection that was administered once every 2 weeks, intramuscularly. UZEDY is to be administered subcutaneously. b Patients received double-blind treatment with another risperidone long-acting injection, given once every 2 weeks, or placebo in addition to continuing their treatment as usual, which included mood stabilizers, antidepressants, and/or anxiolytics. c Parkinsonism includes muscle rigidity, hypokinesia, cogwheel rigidity, and bradykinesia. d Dyskinesia includes muscle twitching and dyskinesia. e Sedation includes sedation and somnolence. Other Adverse Reactions Observed During the Clinical Trial Evaluations of Oral Risperidone The following is a list of additional adverse drug reactions that have been reported during the clinical trial evaluation of oral risperidone: 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, chest discomfort, chest pain, influenza-like illness, pitting edema, edema, chills, sluggishness, malaise, 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, Connective Tissue, and Bone Disorders: joint swelling, joint stiffness, musculoskeletal chest pain, posture abnormal, myalgia, neck pain, muscular weakness, muscle rigidity, rhabdomyolysis, torticollis 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, 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, 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, acne, hyperkeratosis, seborrheic dermatitis, rash generalized, rash maculopapular Vascular Disorders: hypotension, flushing Additional Adverse Reactions Reported With Another Risperidone Long-Acting Injection, Given Once Every 2 Weeks The following is a list of additional adverse reactions that have been reported during the premarketing evaluation of another risperidone long-acting injection, given once every 2 weeks, regardless of frequency of occurrence: Cardiac Disorders: bradycardia, tachycardia, palpitations Ear and Labyrinth Disorders: vertigo Eye Disorders: blepharospasm Gastrointestinal Disorders: toothache, tongue spasm, diarrhea, vomiting, abdominal pain upper, abdominal pain, stomach discomfort General Disorders and Administration Site Conditions: pain, injection site pain, induration, injection site induration, injection site swelling, injection site reaction Infections and Infestations: lower respiratory tract infection, infection, gastroenteritis, subcutaneous abscess, nasopharyngitis, urinary tract infection, rhinitis, sinusitis Injury and Poisoning: fall, procedural pain Investigations: weight decreased, gamma-glutamyltransferase increased, hepatic enzyme increased, aspartate aminotransferase increased, electrocardiogram QT prolonged, glucose urine present Musculoskeletal, Connective Tissue, and Bone Disorders: buttock pain, back pain Nervous System Disorders: convulsion, paresthesia, dystonia, drooling, dizziness postural, akinesia, hypokinesia Psychiatric Disorders: depression, insomnia, anxiety, initial insomnia Reproductive System and Breast Disorders: oligomenorrhea, breast discomfort, menstruation delayed, ejaculation delayed Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, pharyngolaryngeal pain, dyspnea, rhinorrhea Skin and Subcutaneous Tissue Disorders: eczema, rash, pruritis generalized Vascular Disorders: hypertension, orthostatic hypotension Discontinuations Due to Adverse Drug Reactions with Oral Risperidone Schizophrenia Approximately 7% (39/564) of oral risperidone-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 oral risperidone-treated patients were: Table 10: Adverse Reactions Associated with Discontinuation in ≥2% of Oral Risperidone-Treated Adult Patients in Schizophrenia Trials Oral Risperidone Adverse Reaction 2 mg to 8 mg per day (N=366) >8 mg to 16 mg per 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% Discontinuation for extrapyramidal symptoms (including Parkinsonism, akathisia, dystonia, and tardive dyskinesia) was 1% in placebo-treated patients, and 3.4% in active control-treated patients in a double-blind, placebo- and active-controlled trial. Discontinuations Due to Adverse Drug Reactions with Another Long-Acting Injection Risperidone, Given Once Every 2 Weeks Bipolar Disorder In a 24-month double-blind, placebo-controlled treatment period of the trial assessing the efficacy and safety of another risperidone long-acting injection, given once every 2 weeks, monotherapy for maintenance treatment in patients with bipolar I disorder, 1 (0.6%) of 154 patients treated with another risperidone long-acting injection, given once every 2 weeks, discontinued due to an adverse reaction (hyperglycemia). In the 52-week double-blind phase of the placebo-controlled trial in which patients treated with another risperidone long-acting injection, given once every 2 weeks, was administered as adjunctive therapy to patients with bipolar disorder in addition to continuing with their usual treatment, approximately 4% (3/72) of patients treated with another risperidone long-acting injection, given once every 2 weeks, discontinued treatment due to an adverse event, compared with 1.5% (1/67) of placebo-treated patients. Adverse reactions associated with discontinuation in patients treated with another risperidone long-acting injection, given once every 2 weeks, were hypokinesia (one patient) and tardive dyskinesia (one patient). Dose Dependency of Adverse Reactions in Clinical Trials of Oral Risperidone Extrapyramidal Symptoms Data from two fixed-dose trials in adults with schizophrenia provided evidence of dose-relatedness for extrapyramidal symptoms associated with oral risperidone treatment. Two methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 4 fixed doses of oral risperidone (2, 6, 10, and 16 mg/day), including a Parkinsonism score (mean change from baseline) from the Extrapyramidal Symptom Rating Scale, and incidence of spontaneous complaints of EPS: Table 11: Extrapyramidal Symptoms Associated with Oral Risperidone-Treated Adult Patients in an 8-Week Fixed Dose Schizophrenia Trial Dose Groups Placebo Oral Risperidone 2 mg Oral Risperidone 6 mg Oral Risperidone 10 mg Oral Risperidone 16 mg Parkinsonism 1.2 0.9 1.8 2.4

2.6 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 oral risperidone (1, 4, 8, 12, and 16 mg/day): Table 12: Extrapyramidal Symptoms Associated with Oral Risperidone-Treated Adult Patients in an 8-Week Fixed Dose Schizophrenia Trial Dose Groups Oral Risperidone 1 mg Oral Risperidone 4 mg Oral Risperidone 8 mg Oral Risperidone 12 mg Oral Risperidone 16 mg Parkinsonism 0.6 1.7 2.4 2.9

4.1 EPS Incidence 7% 12% 17% 18% 20%

Changes in Body Weight Weight gain was observed in short-term, controlled trials and longer-term uncontrolled studies in adults. Dystonia 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 reaction data elicited by a checklist for side effects from a large study comparing 5 fixed doses of oral risperidone (1, 4, 8, 12, and 16 mg/day) were explored for dose-relatedness of adverse events. A Cochran-Armitage Test for trend in these data revealed a positive trend (p<0.05) for the following adverse reactions: somnolence, vision abnormal, dizziness, palpitations, weight increase, erectile dysfunction, ejaculation disorder, sexual function abnormal, fatigue, and skin discoloration. Changes in ECG Between-group comparisons for pooled placebo-controlled trials of oral risperidone in adults revealed no statistically significant differences between oral risperidone and placebo in mean changes from baseline in ECG parameters, including QT, QTc, and PR intervals, and heart rate. When all oral risperidone 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 oral risperidone were associated with a higher mean increase in heart rate compared to placebo (4 to 6 beats per minute). The ECGs of 227 patients with Bipolar I Disorder were evaluated in the 24-month double-blind, placebo-controlled period. There were no clinically relevant differences in QTc intervals (using Fridericia's and linear correction factors) during treatment with another risperidone long-acting injection, given once every 2 weeks, compared to placebo. The ECGs of 85 patients with bipolar disorder were evaluated in the 52-week double-blind, placebo-controlled trial. There were no statistically significant differences in QTc intervals (using Fridericia's and linear correction factors) during adjunctive treatment with either another risperidone long-acting injection (25 mg, 37.5 mg, or 50 mg), given once every 2 weeks, or placebo in addition to treatment as usual. Injection Site Reactions with UZEDY Local tolerability assessments were administered to patients who reported injection site adverse reactions in a randomized withdrawal study with UZEDY in adult patients with schizophrenia. The injection site was assessed by appropriately trained personnel throughout the clinical development program. All injection site reactions (nodule, pruritus, erythema, mass, and swelling) were mild to moderate in severity with the exception of 1 case of severe pruritus which resolved after 6 days. Injection site reactions were reported in 22 patients (13%) in the placebo group, 36 patients (20%) in the UZEDY once monthly group, and 37 patients (21%) in the UZEDY once every 2 months group. The most common injection site reactions were: nodule (7% in each UZEDY-treated group and 3% in the placebo group) and pruritus (5% and 3% in the UZEDY-treated once monthly and once every 2 months groups, respectively, and 2% in the placebo group).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of oral 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. In addition, the following adverse reactions have been observed during postapproval use of UZEDY: injection site pain. In addition, the following adverse reactions have been observed during postapproval use of another risperidone long-acting injection, given intramuscularly once every 2 weeks: cerebrovascular disorders, including cerebrovascular accidents, and diabetes mellitus aggravated. Retinal artery occlusion after injection of another risperidone long-acting injection, given intramuscularly once every 2 weeks, has been reported during postmarketing surveillance. This has been reported in the presence of abnormal arteriovenous anastomosis. Serious injection site reactions including abscess, cellulitis, cyst, hematoma, necrosis, nodule, and ulcer have been reported with another risperidone long-acting injection, given intramuscularly once every 2 weeks, during postmarketing surveillance. Isolated cases required surgical intervention. Very rarely, cases of anaphylactic reaction after injection with another risperidone long-acting injection, given intramuscularly once every 2 weeks, have been reported during postmarketing experience in patients who have previously tolerated oral risperidone. 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.