RISPERIDONE

6.3 Commonly-Observed Side Effects in Double-Blind, Placebo-Controlled Clinical Trials-Autistic Disorder

Table 9 lists the adverse reactions reported in 5% or more of risperidone-treated pediatric patients treated for irritability associated with autistic disorder in two 8-week, double-blind, placebo-controlled trials.

*Parkinsonism includes musculoskeletal stiffness, extrapyramidal disorder, muscle rigidity, cogwheel rigidity, and muscle tightness.

In another study with patients treated for irritability associated with autistic disorder, headache (6%), epistaxis (6%) and pyrexia (6%) were also observed in risperidone-treated pediatric subjects.

6.4 Other Side Effects Observed During the Premarketing Evaluation of Risperidone

The following adverse reactions occurred in < 1% of the adult patients and in < 5% of the pediatric patients treated with risperidone in the above double-blind, placebo-controlled clinical trial data sets. In addition, the following also includes adverse reactions reported in  risperidone-treated patients who participated in other studies, including double-blind, active-controlled and open-label studies in schizophrenia and bipolar mania studies in pediatric patients with psychiatric disorders other than schizophrenia, bipolar mania, or autistic disorder, and studies in elderly patients with dementia.

Blood and Lymphatic System Disorders: 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: 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

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: polydipsia, anorexia

Musculoskeletal and Connective Tissue Disorders: joint swelling, musculoskeletal chest pain, posture abormal, myalgia, neck pain, muscular weakness, rhabdomyolysis

Nervous System Disorders: balance disorder, disturbance in attention, dysarthria, unresponsive to stimuli, depressed level of consciousness, movement disorder, hypersomnia, transient ischemic attack, coordination abnormal, cerebrovascular accident, speech disorder, 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, sleep disorder, listless, libido decreased, anorgasmia

Renal and Urinary Disorders: enuresis, dysuria, pollakiuria

Reproductive System and Breast Disorders: menstruation irregular, amenorrhea, gynecomastia, 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

Vascular Disorders: flushing

6.5 Discontinuations Due to Side Effects

6.6 Dose Dependency of Side Effects 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 treatment.

Two methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 4 fixed doses of risperidone (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:

Similar methods were used to measure extrapyramidal symptoms (EPS) in an 8-week trial comparing 5 fixed doses of risperidone (1, 4, 8, 12, and 16 mg/day):

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 (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.

6.7 Changes in ECG

6.8 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 possible to reliably estimate their frequency: agranulocytosis, alopecia, anaphylactic reaction, angioedema, atrial fibrillation, blood cholesterol increased, blood triglycerides increased, diabetes mellitus, diabetic ketoacidosis in patients with impaired glucose metabolism, drug withdrawal syndrome neonatal, dysgeusia, hypoglycemia, hypothermia, inappropriate antidiuretic hormone secretion, intestinal obstruction, jaundice, mania, pancreatitis, priapism, QT prolongation, sleep apnea syndrome, thrombocytopenia, urinary retention, and water intoxication.

Other adverse events reported since market introduction, which were temporally related to risperidone but not necessarily causally related, include the following: pituitary adenoma, pulmonary embolism, precocious puberty, cardiopulmonary arrest, and sudden death.

7 DRUG INTERACTIONS

7.1 Centrally-Acting Drugs and Alcohol

7.2 Drugs with Hypotensive Effects

7.3 Levodopa and Dopamine Agonists

7.4 Amitriptyline

Amitriptyline did not affect the pharmacokinetics of risperidone or risperidone and 9-hydroxyrisperidone combined.

7.5 Cimetidine and Ranitidine

7.6 Clozapine

Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.

7.7 Lithium

7.8 Valproate

7.9 Digoxin

7.10 Drugs That Inhibit CYP 2D6 and Other CYP Isozymes

7.11 Carbamazepine and Other Enzyme Inducers

Carbamazepine co-administration decreased the steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone by about 50%. Plasma concentrations of carbamazepine did not appear to be affected. The dose of risperidone may need to be titrated accordingly for patients receiving carbamazepine, particularly during initiation or discontinuation of carbamazepine therapy. Co-administration of other known enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital) with risperidone may cause similar decreases in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone, which could lead to decreased efficacy of risperidone treatment.

7.12 Drugs Metabolized by CYP 2D6

In vitro studies indicate that risperidone is a relatively weak inhibitor of CYP 2D6. Therefore, risperidone is not expected to substantially inhibit the clearance of drugs that are metabolized by this enzymatic pathway. In drug interaction studies, risperidone did not significantly affect the pharmacokinetics of donepezil and galantamine, which are metabolized by CYP 2D6.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.
The teratogenic potential of risperidone was studied in three Segment II studies in Sprague- Dawley and Wistar rats (0.63 to 10 mg/kg or 0.4 to 6 times the maximum recommended human dose [MRHD] on a mg/m² basis) and in one Segment II study in New Zealand rabbits (0.31 to 5 mg/kg or 0.4 to 6 times the MRHD on a mg/m² basis). The incidence of malformations was not increased compared to control in offspring of rats or rabbits given 0.4 to 6 times the MRHD on a mg/m² basis. In three reproductive studies in rats (two Segment III and a multigenerational study), there was an increase in pup deaths during the first 4 days of lactation at doses of 0.16 to 5 mg/kg or 0.1 to 3 times the MRHD on a mg/m² basis. It is not known whether these deaths were due to a direct effect on the fetuses or pups or to effects on the dams.

There was no no-effect dose for increased rat pup mortality. In one Segment III study, there was an increase in stillborn rat pups at a dose of 2.5 mg/kg or 1.5 times the MRHD on a mg/m² basis. In a cross-fostering study in Wistar rats, toxic effects on the fetus or pups, as evidenced by a decrease in the number of live pups and an increase in the number of dead pups at birth (Day 0), and a decrease in birth weight in pups of drug-treated dams were observed. In addition, there was an increase in deaths by Day 1 among pups of drug-treated dams, regardless of whether or not the pups were cross-fostered. Risperidone also appeared to impair maternal behavior in that pup body weight gain and survival (from Day 1 to 4 of lactation) were reduced in pups born to control but reared by drug-treated dams. These effects were all noted at the one dose of risperidone tested, i.e., 5 mg/kg or 3 times the MRHD on a mg/m² basis.

Placental transfer of risperidone occurs in rat pups. There are no adequate and well-controlled studies in pregnant women. However, there was one report of a case of agenesis of the corpus callosum in an infant exposed to risperidone in utero. The causal relationship to risperidone therapy is unknown.

Non-Teratogenic Effects

Neonates exposed to antipsychotic drugs (including risperidone) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Risperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

10.1 Human Experience

Premarketing experience included eight reports of acute risperidone overdosage with estimated doses ranging from 20 to 300 mg and no fatalities. In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. One case, involving an estimated overdose of 240 mg, was associated with hyponatremia, hypokalemia, prolonged QT, and widened QRS. Another case, involving an estimated overdose of 36 mg, was associated with a seizure.

Post-marketing experience includes reports of acute risperidone overdosage, with estimated doses of up to 360 mg. In general, the most frequently reported signs and symptoms are those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Other adverse reactions reported since market introduction related to risperidone overdose include prolonged QT interval and convulsions. Torsade de pointes has been reported in association with combined overdose of risperidone and paroxetine.

10.2 Management of Overdosage

In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.

The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of QT-prolonging effects that might be additive to those of risperidone. Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of risperidone, resulting in problematic hypotension.

There is no specific antidote to risperidone. Therefore, appropriate supportive measures should be instituted. The possibility of multiple drug involvement should be considered. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of risperidone-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

The clinical effect from risperidone results from the combined concentrations of risperidone and its major metabolite, 9-hydroxyrisperidone [see Clinical Pharmacology (12.3)]. Antagonism at receptors other than D₂ and 5HT₂ [see Clinical Pharmacology (12.1)] may explain some of the other effects of risperidone.

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Schizophrenia

14.2 Bipolar Mania - Monotherapy

Adults
The efficacy of risperidone in the treatment of acute manic or mixed episodes was established in two short-term (3-week) placebo-controlled trials in patients who met the DSM-IV criteria for Bipolar I Disorder with manic or mixed episodes. These trials included patients with or without psychotic features.

The primary rating instrument used for assessing manic symptoms in these trials was the Young Mania Rating Scale (YMRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology (irritability, disruptive/aggressive behavior, sleep, elevated mood, speech, increased activity, sexual interest, language/thought disorder, thought content, appearance, and insight) in a range from 0 (no manic features) to 60 (maximum score). The primary outcome in these trials was change from baseline in the YMRS total score. The results of the trials follow:

(1) In one 3-week placebo-controlled trial (n=246), limited to patients with manic episodes, which involved a dose range of risperidone 1 to 6 mg/day, once daily, starting at 3 mg/day (mean modal dose was 4.1 mg/day), risperidone was superior to placebo in the reduction of YMRS total score.

(2) In another 3-week placebo-controlled trial (n=286), which involved a dose range of 1 to 6 mg/day, once daily, starting at 3 mg/day (mean modal dose was 5.6 mg/day), risperidone was superior to placebo in the reduction of YMRS total score.

Pediatrics
The efficacy of risperidone in the treatment of mania in children or adolescents with Bipolar I disorder was demonstrated in a 3-week, randomized, double-blind, placebo-controlled, multicenter trial including patients ranging in ages from 10 to 17 years who were experiencing a manic or mixed episode of bipolar I disorder. Patients were randomized into one of three treatment groups: risperidone 0.5 to 2.5 mg/day (n = 50, mean modal dose = 1.9 mg), risperidone 3 to 6 mg/day (n = 61, mean modal dose = 4.7 mg), or placebo (n = 58). In all cases, study medication was initiated at 0.5 mg/day and titrated to the target dosage range by Day 7, with further increases in dosage to the maximum tolerated dose within the targeted dose range by Day 10. The primary rating instrument used for assessing efficacy in this study was the mean change from baseline in the total YMRS score.

Results of this study demonstrated efficacy of risperidone in both dose groups compared with placebo, as measured by significant reduction of total YMRS core. The efficacy on the primary parameter in the 3 to 6 mg/day dose group was comparable to the 0.5 to 2.5 mg/day dose group. Doses higher than 2.5 mg/day did not reveal any trend towards greater efficacy.

14.3 Bipolar Mania - Combination Therapy

The efficacy of risperidone with concomitant lithium or valproate in the treatment of acute manic or mixed episodes was established in one controlled trial in adult patients who met the DSM-IV criteria for Bipolar I Disorder. This trial included patients with or without psychotic features and with or without a rapid-cycling course.

(1) In this 3-week placebo-controlled combination trial, 148 in-or outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms were randomized to receive risperidone, placebo, or an active comparator, in combination with their original therapy. Risperidone, in a dose range of 1 to 6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.8 mg/day), combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1.4 mEq/L or 50 mcg/mL to 120 mcg/mL, respectively) was superior to lithium or valproate alone in the reduction of YMRS total score.

(2) In a second 3-week placebo-controlled combination trial, 142 in- or outpatients on lithium, valproate, or carbamazepine therapy with inadequately controlled manic or mixed symptoms were randomized to receive risperidone or placebo, in combination with their original therapy. Risperidone, in a dose range of 1 to 6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.7 mg/day), combined with lithium, valproate, or carbamazepine (in therapeutic ranges of 0.6 mEq/L to 1.4 mEq/L for lithium, 50 mcg/mL to 125 mcg/mL for valproate, or 4 to 12 mcg/mL for carbamazepine, respectively) was not superior to lithium, valproate, or carbamazepine alone in the reduction of YMRS total score. A possible explanation for the failure of this trial was induction of risperidone and 9-hydroxyrisperidone clearance by carbamazepine, leading to subtherapeutic levels of risperidone and 9-hydroxyrisperidone.

14.4 Irritability Associated with Autistic Disorder

16 HOW SUPPLIED/STORAGE AND HANDLING

Storage and Handling

17 PATIENT COUNSELING INFORMATION

17.1 Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, especially during the period of initial dose titration [see Warnings and Precautions (5.7)].

17.2 Interference with Cognitive and Motor Performance

17.3 Pregnancy

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1)].

17.4 Nursing

Patients should be advised not to breast-feed an infant if they are taking risperidone [see Use in Specific Populations (8.3)].

17.5 Concomitant Medication

17.6 Alcohol

Patients should be advised to avoid alcohol while taking risperidone [see Drug Interactions (7.1)].

Manufactured by:
Wockhardt Limited,
Mumbai, India.

Distributed by:
Wockhardt USA LLC.
20 Waterview Blvd.
Parsippany, NJ 07054
USA.

Rev.101011

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-553 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 0.25 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE FERRIC OXIDE YELLOW propylene glycol FERROSOFERRIC OXIDE ferric oxide red talc Product Characteristics Color Size Imprint Code Shape yellow (yellow) 6 mm W;R CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-553-01 30 in 1 BOTTLE 2 NDC:64679-553-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-553-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-554 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 0.5 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE ferric oxide red propylene glycol talc titanium dioxide Product Characteristics Color Size Imprint Code Shape brown (brown) 9 mm W;554 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-554-01 30 in 1 BOTTLE 2 NDC:64679-554-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-554-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-555 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 1 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE propylene glycol Product Characteristics Color Size Imprint Code Shape white (white) 12 mm W555 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-555-01 30 in 1 BOTTLE 2 NDC:64679-555-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-555-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-557 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 2 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE titanium dioxide propylene glycol FD&C YELLOW NO. 6 talc Product Characteristics Color Size Imprint Code Shape orange (orange) 12 mm W557 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-557-01 30 in 1 BOTTLE 2 NDC:64679-557-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-557-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-571 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 3 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE D&C YELLOW NO. 10 propylene glycol titanium dioxide FERRIC OXIDE YELLOW talc Product Characteristics Color Size Imprint Code Shape yellow (yellow) 13 mm W571 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-571-01 30 in 1 BOTTLE 2 NDC:64679-571-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-571-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09

RISPERIDONE RISPERIDONE TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:64679-572 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RISPERIDONE RISPERIDONE 4 mg Inactive Ingredients Ingredient Name Strength SODIUM LAURYL SULFATE lactose monohydrate cellulose, microcrystalline SODIUM STARCH GLYCOLATE TYPE A POTATO HYPROMELLOSES SILICON DIOXIDE MAGNESIUM STEARATE D&C YELLOW NO. 10 propylene glycol FD&C BLUE NO. 2 titanium dioxide talc Product Characteristics Color Size Imprint Code Shape green (green) 14 mm W572 CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:64679-572-01 30 in 1 BOTTLE 2 NDC:64679-572-02 500 in 1 BOTTLE 3 10 in 1 BLISTER PACK 4 NDC:64679-572-04 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078871 2008-10-09