RISPERIDONE tablet

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Active ingredient:
RISPERIDONE (UNII: L6UH7ZF8HC) (RISPERIDONE - UNII:L6UH7ZF8HC)
Available from:
RPK Pharmaceuticals, Inc.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Risperidone tablets are indicated for the treatment of schizophrenia. Efficacy was established in 4 short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term maintenance trial in adults [see Clinical Studies (14.1)] . Monotherapy Risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder. Efficacy was established in 2 short-term trials in adults and one short-term trial in children and adolescents (ages 10 to 17 years) [see Clinical Studies (14.2)] . Adjunctive Therapy Risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder. Efficacy was established in one short-term trial in adults [ see Clinical Studies (14.3)]. Risperidone tablets are indicated for the treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, tem
Product summary:
Product: 53002-1596 NDC: 53002-1596-3 30 TABLET in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
53002-1596-3

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RISPERIDONE- risperidone tablet

RPK Pharmaceuticals, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use RISPERIDONE TABLETS safely and

effectively. See full prescribing information for RISPERIDONE TABLETS.

RISPERIDONE Tablets, for oral use

Initial U.S. Approval 1993

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-

RELATED PSYCHOSIS

See full prescribing information for complete boxed warning.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk

of death. Risperidone is not approved for the treatment of patients with dementia-related psychosis. [see

Warnings and Precautions (5.1)]

INDICATIONS AND USAGE

Risperidone is an atypical antipsychotic indicated for:

Treatment of schizophrenia (1.1)

As monotherapy or adjunctive therapy with lithium or valproate, for the treatment of acute manic or mixed episodes

associated with Bipolar I Disorder (1.2)

Treatment of irritability associated with autistic disorder (1.3)

DOSAGE AND ADMINISTRATION

Recommended daily dosage:

Initial Dose

Target Dose Effective Dose Range

Schizophrenia

: adults (2.1)

2 mg

4 to 8 mg

4 to 16 mg

Schizophrenia

: adolescents

(2.1)

0.5 mg

3 mg

1 to 6 mg

Bipolar

mania: Adults (2.2)

2 to 3 mg

1 to 6 mg

1 to 6 mg

Bipolar

mania: in children and adolescents (2.2)

0.5 mg

1 to 2.5

1 to 6 mg

Irritability associated

with autistic disorder (2.3)

0.25 mg (Weight <

20 kg)

0.5 mg (Weight

≥20 kg)

0.5 mg

(<20 kg)

1 mg

(≥20 kg)

0.5 to 3 mg

Severe Renal or Hepatic Impairment in Adults: Use a lower starting dose of 0.5 mg twice daily. May increase to dosages

above 1.5 mg twice daily at intervals of at one week or longer. (2.4)

DOSAGE FORMS AND STRENGTHS

Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to risperidone, paliperidone, or to any excipients in risperidone (4)

WARNINGS AND PRECAUTIONS

Cerebrovascular events, including stroke, in elderly patients with dementia- related psychosis. Risperidoneis not

approved for use in patients with dementia-related psychosis (5.2)

Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of risperidone and close monitoring. (5.3)

Tardive dyskinesia: Consider discontinuing risperidone if clinically indicated. (5.4)

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.

(5.5)

o 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. (5.5)

o Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.

(5.5)

o Weight Gain: Significant weight gain has been reported. Monitor weight gain. (5.5)

Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration. (5.6)

Orthostatic hypotension: For patients at risk, consider a lower starting dose and slower titration. (5.7)

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 if a clinically significant decline in WBC

occurs in the absence of other causative factors. (5.9)

Potential for cognitive and motor impairment: Use caution when operating machinery. (5.10)

Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.

(5.11)

ADVERSE REACTIONS

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 Torrent Pharma Inc. at 1-800-912-9561 or FDA at 1-

800-FDA-1088, or www.fda.gov/medwatch

DRUG INTERACTIONS

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. Increase the risperidone

dose up to double the patient's usual dose. Titrate slowly. (7.1)

Fluoxetine, paroxetine, and other CYP 2D6 enzyme inhibitors increase plasma concentrations of risperidone. Reduce

the initial dose. Do not exceed a final dose of 8 mg per day of risperidone. (7.1)

USE IN SPECIFIC POPULATIONS

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. (8.1)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 12/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING : INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-

RELATED PSYCHOSIS

1 INDICATIONS AND USAGE

1.1 Schizophrenia

1.2 Bipolar Mania

1.3 Irritability Associated with Autistic Disorder

2 DOSAGE AND ADMINISTRATION

2.1 Schizophrenia

2.2 Bipolar Mania

2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

2.5 Dose Adjustments for Specific Drug Interactions

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis

5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-

Related Psychosis

5.3 Neuroleptic Malignant Syndrome

5.4 Tardive Dyskinesia

5.5 Metabolic Changes

5.6 Hyperprolactinemia

5.7 Orthostatic Hypotension

5.8 Falls

5.9 Leukopenia, Neutropenia, and Agranulocytosis

5.10 Potential for Cognitive and Motor Impairment

5.11 Seizures

5.12 Dysphagia

5.13 Priapism

5.14 Body Temperature Regulation

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Pharmacokinetic-related Interactions

7.2 Pharmacodynamic-related Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 PREGNANCY

8.2 Lactation

8.3 Females and Males of Reproductive Potential

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

8.8 Patients with Parkinson’s Disease or Lewy Body Dementia

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

10.1 Human Experience

10.2 Management of Overdosage

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Schizophrenia

14.2 Bipolar Mania - Monotherapy

14.3 Bipolar Mania – Adjunctive Therapy with Lithium or Valproate

14.4 Irritability Associated with Autistic Disorder

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

WARNING : 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. Risperidone is not approved for the treatment of patients with

dementia-related psychosis. [See Warnings and Precautions (5.1)]

1 INDICATIONS AND USAGE

1.1 Schizophrenia

Risperidone tablets are indicated for the treatment of schizophrenia. Efficacy was established in 4

short-term trials in adults, 2 short-term trials in adolescents (ages 13 to 17 years), and one long-term

maintenance trial in adults [see Clinical Studies (14.1)].

1.2 Bipolar Mania

Monotherapy

Risperidone tablets are indicated for the treatment of acute manic or mixed episodes associated with

Bipolar I Disorder. Efficacy was established in 2 short-term trials in adults and one short-term trial in

children and adolescents (ages 10 to 17 years) [see Clinical Studies (14.2)].

Adjunctive Therapy

Risperidone tablets adjunctive therapy with lithium or valproate is indicated for the treatment of acute

manic or mixed episodes associated with Bipolar I Disorder. Efficacy was established in one short-

term trial in adults [see Clinical Studies (14.3)].

1.3 Irritability Associated with Autistic Disorder

Risperidone tablets are indicated for the treatment of irritability associated with autistic disorder,

including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and

quickly changing moods. Efficacy was established in 3 short-term trials in children and adolescents

(ages 5 to 17 years) [see Clinical Studies (14.4)].

2 DOSAGE AND ADMINISTRATION

Table 1. Recommended Daily Dosage by Indication

Initial Dose

Titration

(Increments)

Target Dose

Effective

Dose

Range

Schizophrenia: adults

(2.1)

2 mg

1 to 2 mg

4 to 8 mg

4 to 16 mg

Schizophrenia:

adolescents

(2.2)

0.5 mg

0.5 to 1 mg

3 mg

1 to 6 mg

Bipolar mania: adults

(2.2)

2 to 3 mg

1 mg

1 to 6 mg

1 to 6 mg

Bipolar mania:

children and

0.5 mg

0.5 to 1 mg

1 to 2.5 mg

1 to 6 mg

adolescents (2.2)

Irritability in autistic

disorder (2.3)

0.25 mg

Can increase to

0.5 mg by Day 4:

(body weight less

than 20 kg)

0.5 mg

Can increase to

1 mg by Day 4:

(body weight

greater than or

equal to 20 kg)

After Day 4, at

intervals of > 2

weeks:

0.25 mg

(body weight

less

than 20 kg)

0.5 mg

(body weight

greater than or

equal to 20 kg)

0.5 mg:

(body weight less

than 20 kg)

1 mg:

(body weight

greater than or

equal to 20 kg)

0.5 to 3 mg

Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily. May

increase to dosages above 1.5 mg twice daily at intervals of one week or longer.

2.1 Schizophrenia

Adults

Usual Initial Dose

Risperidone tablets can be administered once or twice daily. Initial dosing is 2 mg per day. May

increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to

a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate.

Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per

day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were

associated with more extrapyramidal symptoms and other adverse effects, and are generally not

recommended. In a single study supporting once-daily dosing, the efficacy results were generally

stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in

clinical trials [see Clinical Studies (14.1)].

Adolescents

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening.

The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day,

as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in

studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional

benefit was observed above 3 mg per day, and higher doses were associated with more adverse events.

Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice

daily.

Maintenance Therapy

While it is unknown how long a patient with schizophrenia should remain on risperidone tablets, the

effectiveness of risperidone tablets 2 mg per day to 8 mg per day at delaying relapse was demonstrated

in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then

followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Both adult and adolescent patients who

respond acutely should generally be maintained on their effective dose beyond the acute episode.

Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that after

an interval off risperidone tablets, the initial titration schedule should be followed.

Switching From Other Antipsychotics

There are no systematically collected data to specifically address switching schizophrenic patients

from other antipsychotics to risperidone tablets, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual Dose

Adults

The initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or

greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in

the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was

demonstrated in a flexible dosage range of 1 mg to 6 mg per day [see Clinical Studies (14.2, 14.3)].

Risperidone tablet doses higher than 6 mg per day were not studied.

Pediatrics

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening.

The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day,

as tolerated, to the recommended target dose of 1 mg to 2.5 mg per day. Although efficacy has been

demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per

day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with

more adverse events. Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice

daily.

Maintenance Therapy

There is no body of evidence available from controlled trials to guide a clinician in the longer-term

management of a patient who improves during treatment of an acute manic episode with risperidone

tablets. While it is generally agreed that pharmacological treatment beyond an acute response in mania is

desirable, both for maintenance of the initial response and for prevention of new manic episodes, there

are no systematically obtained data to support the use of risperidone tablets in such longer-term

treatment (i.e., beyond 3 weeks). The physician who elects to use risperidone tablets for extended

periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual

patient.

2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)

The dosage of risperidone tablets should be individualized according to the response and tolerability

of the patient. The total daily dose of risperidone tablets can be administered once daily, or half the total

daily dose can be administered twice daily.

For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body

weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days,

the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and

1.0 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days.

In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks

or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day

for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No

dosing data are available for children who weigh less than 15 kg.

Once sufficient clinical response has been achieved and maintained, consider gradually lowering the

dose to achieve the optimal balance of efficacy and safety. The physician who elects to use risperidone

tablets for extended periods should periodically re-evaluate the long-term risks and benefits of the drug

for the individual patient.

Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime

or administering half the daily dose twice daily, or a reduction of the dose.

or administering half the daily dose twice daily, or a reduction of the dose.

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10 to 15 points on

Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in

increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in

intervals of one week or greater [see Use in Specific Populations (8.6 and 8.7)].

2.5 Dose Adjustments for Specific Drug Interactions

When risperidone tablets are co-administered with enzyme inducers (e.g., carbamazepine), the dose of

risperidone tablets should be increased up to double the patient's usual dose. It may be necessary to

decrease the risperidone tablets dose when enzyme inducers such as carbamazepine are discontinued

[see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of risperidone

tablets with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).

When fluoxetine or paroxetine is co-administered with risperidone tablets, the dose of risperidone

tablets should be reduced. The risperidone tablets dose should not exceed 8 mg per day in adults when

co-administered with these drugs. When initiating therapy, risperidone tablets should be titrated slowly.

It may be necessary to increase the risperidone tablets dose when enzyme inhibitors such as fluoxetine

or paroxetine are discontinued [see Drug Interactions (7.1)].

3 DOSAGE FORMS AND STRENGTHS

Risperidone tablets, USP are available in following strengths and colors: 0.25 mg (yellow), 0.5 mg

(red), 1 mg (white to off white), 2 mg (Light orange), 3 mg (yellow), and 4 mg (yellow). All are oblong

shaped, and debossed with 0.25mg on one side and '1035' on other side for 0.25mg; 'R 0.50' on one side

and '1036'on other side for 0.5mg; 'R 1' on one side and '1037'on other side for 1mg; R 2' on one side

and '1038'on other side for 2mg; 'R 3' on one side and '1039'on other side for 3mg and 'R 4' on one side

and '1040'on other side for 4mg.

4 CONTRAINDICATIONS

Risperidone is contraindicated in patients with a known hypersensitivity to either risperidone or

paliperidone, or to any of the excipients in the risperidone 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.

5 WARNINGS AND PRECAUTIONS

5.1 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. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks),largely in patients

taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to

1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled

trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the

placebo group. Although the causes of death were varied, most of the deaths appeared to be either

cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., 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.

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 when

compared to patients treated with risperidone 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 is not approved for the treatment of dementia-related psychosis [see Boxed Warning].

5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-

Related Psychosis

Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were

reported in patients (mean age 85 years; range 73 to 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 is not approved for the treatment of patients with dementia-related psychosis. [see

Boxed Warning and Warnings and Precautions (5.1)]

5.3 Neuroleptic Malignant Syndrome

Antipsychotic drugs including risperidone can cause a potentially fatal symptom complex referred to as

Neuroleptic Malignant Syndrome (NMS). Clinical manifestations of NMS include hyperpyrexia, muscle

rigidity, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia,

diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase

(CPK), myoglobinuria, rhabdomyolysis, and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is

important to identify cases in which the clinical presentation includes both serious medical illness (e.g.,

pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and

symptoms (EPS). Other important considerations in the differential diagnosis include central

anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.

The management of NMS should include: (1) immediate discontinuation of antipsychotic drugs and other

drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring;

and (3) treatment of any concomitant serious medical problems for which specific treatments are

available. There is no general agreement about specific pharmacological treatment regimens for

uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction

of drug therapy should be carefully considered. The patient should be carefully monitored, since

recurrences of NMS have been reported.

5.4 Tardive Dyskinesia

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients

treated with antipsychotic drugs. The risk of developing tardive dyskinesia and the likelihood that it will

become irreversible are believed to increase as the duration of treatment and the total cumulative dose

of antipsychotic drugs administered to the patient increase. However, the syndrome can develop,

although much less commonly, after relatively brief treatment periods at low doses.

The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic

treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome

and thereby may possibly mask the underlying process. The effect that symptomatic suppression has

upon the long-term course of the syndrome is unknown.

Given these considerations, prescribe risperidone in a manner that is most likely to minimize the

occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for

patients who suffer from a chronic illness that: (1) 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, the smallest dose and the shortest duration of

treatment producing a satisfactory clinical response should be sought. The need for continued treatment

should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient treated with risperidone, consider drug

discontinuation. However, some patients may require treatment with risperidone despite the presence of

the syndrome.

5.5 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. 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, should be monitored regularly for worsening of glucose control. Patients with

risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment

with atypical antipsychotics, including risperidone, should undergo fasting blood glucose testing at the

beginning of treatment and periodically during treatment. Any patient treated with atypical

antipsychotics, including risperidone, 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, should undergo fasting blood

glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic, including

risperidone, was discontinued; however, some patients required continuation of anti-diabetic treatment

despite discontinuation of risperidone.

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. Change in Random Glucose from Seven Placebo-Controlled, 3- to 8-

Week, Fixed- or Flexible-Dose Studies in Adult Subjects with Schizophrenia or

Bipolar Mania

Risperidone

Placebo

1 to 8 mg/day

>8 to 16 g/day

Mean change from baseline

(mg/dL)

n=555

n=748

n=164

Serum Glucose

-1.4

Proportion of patients with

shifts

Serum Glucose

(<140 mg/dL to ≥ 200

mg/dL)

0.6%

0.4%

(3/525)

(3/702)

(0/158)

In longer-term, controlled and uncontrolled studies, risperidone was associated with a mean change in

glucose of +2.8 mg/dL at Week 24 (n=151) and +4.1 mg/dL at Week 48 (n=50).

Data from the placebo-controlled 3- to 6-week study in children and adolescents with schizophrenia (13

to 17 years of age), bipolar mania (10 to 17 years of age), or autistic disorder (5 to 17 years of age) are

presented in Table 3.

Table 3. Change in Fasting Glucose from Three Placebo-controlled, 3- to 6-

week, Fixed Dose Studies in Children and Adolescents with Schizophrenia (13 to

17 years of age), Bipolar Mania (10 to 17 years of age), or Autistic Disorder (5 to

17 years of age)

Risperidone

Placebo

0.5 to 6 mg/day

Mean change from baseline (mg/dL)

n=76

n=135

Serum Glucose

-1.3

Proportion of patients with shifts

Serum Glucose

(<100 mg/dL to ≥126

0.8%

mg/dL)

(0/64)

(1/120)

In longer-term, uncontrolled, open-label extension pediatric studies, risperidone was associated with a

mean change in fasting glucose of +5.2 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. Change in Random Lipids from Seven Placebo-Controlled, 3-to 8-Week,

Fixed- or Flexible-Dose Studies in Adult Subjects with Schizophrenia or Bipolar

Mania

Risperidone

Placebo

1 to 8 mg/day

>8 to 16

mg/day

Mean change from baseline

(mg/dL)

Cholesterol

n=559

n=742

n=156

Change from baseline

Triglycerides

n=183

n=307

n=123

Change from baseline

-17.4

-4.9

-8.3

Proportion of patients With Shifts

Cholesterol

2.7%

4.3%

6.3%

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