A-Z Drug Facts > Risperidone

Risperidone

Pronouncation: (ris-PER-i-done)
Class: Benzisoxazole derivative

Trade Names:
Risperdal
- Tablets 0.25 mg
- Tablets 0.5 mg
- Tablets 1 mg
- Tablets 2 mg
- Tablets 3 mg
- Tablets 4 mg
- Solution, oral 1 mg/mL

Trade Names:
Risperdal Consta
- Powder for Injection 25 mg
- Powder for Injection 37.5 mg
- Powder for Injection 50 mg

Trade Names:
Risperdal M-TAB
- Tablets, orally disintegrating 0.5 mg
- Tablets, orally disintegrating 1 mg
- Tablets, orally disintegrating 2 mg
- Tablets, orally disintegrating 3 mg
- Tablets, orally disintegrating 4 mg

Pharmacology

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Has antipsychotic effect, apparently caused by dopamine- and serotonin-receptor blocking in CNS.

Pharmacokinetics

Absorption

PO Absolute oral bioavailability is 70%. T _max is 1 h (risperidone), 3 h (9-hydroxyrisperidone extensive metabolizers), or 20 h (9-hydroxyrisperidone poor metabolizers). Steady state is about 1 day (extensive metabolizers) or about 5 days (poor metabolizers). IM The main release of the drug starts from 3 wk after injection, is maintained from 4 to 6 wk, and subsides by 7 wk.

Distribution

Vd is 1 to 2 L/kg. Protein binding is about 90% (parent compound) or about 77% (9-hydroxyrisperidone). Once absorbed, the IM form is rapidly distributed.

Metabolism

Extensively metabolized in the liver by CYP-450 2D6 to major active metabolite 9-hydroxyrisperidone. 9-hydroxyrisperidone has similar activity as risperidone. CYP-450 2D6 is subject to genetic polymorphism (about 6% to 8% of white patients and a very low percentage of Asian patients have little or no activity and are considered poor metabolizers). Extensive metabolizers have low risperidone and high 9-hydroxyrisperidone concentrations; the opposite is true for poor metabolizers.

Elimination

Eliminated in urine (70%) and feces (14%). PO The t _½ is 3 and 20 h for risperidone extensive and poor metabolizers, respectively; 21 and 30 h for 9-hydroxyrisperidone extensive and poor metabolizers, respectively; or 20 h (overall mean t _½ ) for combined risperidone and 9-hydroxyrisperidone. IM The t _½ of risperidone plus 9-hydroxyrisperidone is 3 to 6 days. The clearance of risperidone and risperidone plus 9-hydroxyrisperidone is 13.7 and 5 L/h, respectively, for extensive metabolizers, and 3.3 and 3.2 L/h, respectively, for poor metabolizers.

Special Populations

Renal Function Impairment

Moderate to severe: Cl of parent drug and active metabolite decreased 60%. Dosage reduction recommended.

Hepatic Function Impairment

Mean free fraction of risperidone in plasma increased about 35%. Dosage reduction recommended.

Elderly

PO Renal Cl of parent drug and active metabolite was decreased. Elimination t _½ was prolonged. Modify dose accordingly. IM No dosing changes required.

Indications and Usage

Treatment of schizophrenia; short-term treatment of acute manic or mixed episodes associated with bipolar disorder as either monotherapy or adjunct therapy to lithium or valproate (oral only); treatment of irritability associated with autistic disorder (oral only).

Unlabeled Uses

(oral only) Treatment of certain behavioral problems in children (with or without autism); improvement of severely disruptive behavior in children with subaverage intelligence; treatment of patients with obsessive-compulsive disorder refractory to SSRIs; treatment of psychosis in patients with Parkinson disease; treatment of tics in patients with Tourette disorder.

Contraindications

Standard considerations.

Dosage and Administration

Schizophrenia
Adults

PO Can be administered on a once- or twice-daily schedule. 1 mg twice daily on first day, 2 mg twice daily on second day, and 3 mg twice daily on third day. Dosage adjustment thereafter should occur at intervals of at least 1 wk in increments of 1 mg twice daily. Efficacy generally occurs in a range of 4 to 8 mg/day (max, 16 mg/day). IM 25 mg every 2 wk (max, 50 mg every 2 wk). Give oral risperidone (or other oral antipsychotic agent) with the first injection and continue for 3 wk to ensure adequate plasma concentrations. Do not make upward dosage adjustments more frequently than every 4 wk.

Bipolar Mania
Adults

PO Initial dose is 2 to 3 mg/day on a once-daily schedule. Adjust dose at intervals of no less than 24 h in increments of 1 mg/day (max, 6 mg/day). No data to support acute treatment beyond 3 wk.

Irritability Associated With Autistic Disorder
Children 5 yr of age and older

PO Can be administered on a once- or twice-daily schedule. Use with caution in children weighing less than 15 kg. For patients less than 20 kg, the initial dose is 0.25 mg/day. After a minimum of 4 days, the dose may be increased to 0.5 mg/day. This dose should be maintained for a minimum of 14 days. If sufficient clinical response is not obtained, the dose may be increased in increments of 0.25 mg/day at intervals of no less than 14 days. For patients 20 kg or more, the initial dose is 0.5 mg/day. After a minimum of 4 days, the dose may be increased to 1 mg/day. This dose should be maintained for a minimum of 14 days. If sufficient clinical response is not obtained, the dose may be increased in increments of 0.5 mg/day at intervals of no less than 14 days.

Special Populations
Elderly and patients with renal or hepatic function impairment who can tolerate at least 2 mg of oral risperidone

IM 25 mg every 2 wk.

Elderly or debilitated patients with severe renal or hepatic function impairment and patients predisposed to hypotension or for whom hypotension may pose a risk

PO 0.5 mg twice daily initially; increase in 0.5 mg increments twice daily thereafter. Increases above 1.5 mg twice daily should generally occur at intervals of at least 1 wk.

General Advice

• Orally disintegrating tablet
• Do not push tablet through foil.
• Using dry hands, remove tablet from blister by peeling back foil and immediately place on tongue.
• Tablets disintegrate within seconds and can be swallowed with or without liquid.
• Do not split or chew tablet.

• Powder for injection
• For IM administration only. Not for intradermal, subcutaneous, IV, or intra-arterial administration.
• Administer by deep IM gluteal injection. Alternate injections between the 2 buttocks.
• Allow dose pack from refrigerator to reach room temperature before reconstituting powder for injection.
• Reconstitute powder for injection following manufacturer's guidelines and supplied diluent.
• Administer suspension immediately after reconstitution. If not administered immediately after reconstitution, the suspension must be administered within 6 h. If injection is not administered immediately after reconstitution, resuspend injection following manufacturer's guidelines

Storage/Stability

Store tablets, orally disintegrating tablets, and oral solution at controlled room temperature (59° to 77°F). Protect tablets from light and moisture. Protect oral solution from light and freezing. Store injection dose pack in refrigerator (36° to 46°F). If refrigeration is unavailable, store at temperatures not exceeding 77°F for no more than 7 days prior to reconstitution. Once in suspension, avoid exposure to temperatures exceeding 77°F. Discard suspension if not administered within 6 h of reconstitution.

Drug Interactions

Alcohol, CNS depressants

May cause additive CNS depressant effects.

Antihypertensives

Risperidone may enhance hypotensive effects of some antihypertensives.

Cimetidine, ranitidine

May increase bioavailability of risperidone.

Enzyme inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin)

Risperidone plasma levels may be reduced, decreasing the efficacy.

Fluoxetine, paroxetine

Risperidone plasma concentrations may be elevated, increasing adverse reactions and risk of serotonin syndrome.

Inhibitors of CYP2D6 (eg, clozapine, indinavir, ritonavir, thioridazine) and other CYP isozymes (eg, indinavir, itraconazole, ketoconazole, ritonavir)

Risperidone plasma levels may be elevated, increasing the therapeutic effects and adverse reactions.

Levodopa and other dopamine agonists

Risperidone may antagonize the effects of levodopa and other dopamine agonists.

Valproate

Peak plasma levels may be increased by risperidone.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Adverse reactions may vary by route (eg, GI adverse reactions more varied and frequent with oral administration) or dosage.

Cardiovascular

Tachycardia (5%); hypertension (3%); hypotension, syncope (2%); atrial fibrillation, cardiopulmonary arrest, cerebrovascular disorder (postmarketing). Children: tachycardia (7%).

CNS

Extrapyramidal symptoms (34%); somnolence (28%); agitation, insomnia (26%); headache (22%); anxiety (20%); dystonia (18%); akathisia (16%); dizziness (11%); parkinsonism (10%); manic reaction (8%); fatigue, hallucinations (7%); suicide attempts (4%); abnormal thinking, aggressive reaction, tremor (3%); abnormal dreams, hypoesthesia, impaired concentration (2%); apathy, asthenia, decreased sexual desire, delusion, depression, hypertonia, increased dream activity, increased sleep duration, nervousness, paranoid reaction, psychosis (at least 1%); aggravation of Parkinson disease, mania (postmarketing). Children: somnolence (67%); fatigue (42%); extrapyramidal symptoms (28%); dystonia, tremor (12%); dizziness (9%); parkinsonism (8%); automatism, dyskinesia (7%); confusion (5%).

Dermatologic

Rash (5%); dry skin (4%); acne, pruritus (2%); seborrhea (1%); increased pigmentation, photosensitivity (at least 1%).

EENT

Rhinitis (14%); abnormal vision (6%); ear disorder, pharyngitis (3%).

GI

Constipation (13%); dyspepsia, nausea (11%); dry mouth, vomiting (7%); increased saliva (6%); diarrhea (5%); abdominal pain, tooth disorder (4%); toothache (3%); anorexia, reduced salivation (at least 1%); intestinal obstruction, pancreatitis (postmarketing). Children: increased appetite (49%); increased salivation (22%); constipation (21%); dry mouth (13%).

Genitourinary

Amenorrhea, erectile dysfunction, menorrhagia, orgastic dysfunction, polydipsia, polyuria, urinary incontinence, vaginal dryness (at least 1%); increased prolactin levels (postmarketing).

Hepatic

Increased hepatic enzymes (at least 1%); jaundice (postmarketing).

Hematologic-Lymphatic

Anemia (1%).

Metabolic-Nutritional

Increased weight (18%); decreased weight (4%); peripheral edema (3%); aggravated diabetes mellitus (including diabetic ketoacidosis), benign pituitary adenomas, hyperglycemia (postmarketing). Children: weight increase (5%); precocious puberty (postmarketing).

Musculoskeletal

Myalgia (5%); leg pain, (4%); arthralgia (3%); back pain, skeletal pain (2%).

Respiratory

Coughing (5%); sinusitis (4%); upper respiratory tract infection (3%); dyspnea (1%); apnea, pulmonary embolism (postmarketing). Children: upper respiratory tract infection (34%).

Miscellaneous

Pain (10%); chest pain, fever (3%); injury (2%); injection-site pain (at least 1%); anaphylactic reaction, angioedema, sudden death (postmarketing).

Precautions

Warnings Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death, compared with placebo. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Risperidone is not approved for the treatment of patients with dementia-related psychosis.

Monitor Monitor orthostatic vital signs in elderly patients. Monitor BP. Regularly monitor patients with established diagnosis of diabetes mellitus for worsening of glucose control.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in children younger than 5 yr of age with autistic disorder. Safety and efficacy not established in children with schizophrenia or bipolar disorder. Safety and efficacy of IM dose not established.

Elderly

Elderly and debilitated patients may have reduced ability to eliminate risperidone. Increased risk of tardive dyskinesia, especially in elderly women. Cerebrovascular adverse reactions and fatalities may occur.

Renal Function

May experience enhanced effects of risperidone because of reduced ability to eliminate risperidone. Dose adjustment may be required.

Hepatic Function

May experience enhanced effects of risperidone because of decreased protein binding. Dose adjustment may be required.

Special Risk Patients

Use with caution in patients with Parkinson disease, dementia with Lewy bodies, or conditions that could affect metabolism or hemodynamic responses.

Antiemetic effect

This effect may mask signs and symptoms of overdosage with certain drugs or conditions such as intestinal obstruction.

Aspiration pneumonia

Antipsychotics have been associated with esophageal dysmotility and aspiration. Use with caution in patients at risk for aspiration pneumonia.

Body temperature regulation

Antipsychotics can disrupt the body's ability to reduce core temperature.

Cardiac effects

Appears to have proarrhythmic effects.

Cerebrovascular adverse events (CVAE)

CVAE (eg, stroke, transient ischemic attack), including fatalities, may occur, especially in elderly patients.

Change in drug therapy

When patient is switched from another antipsychotic to oral risperidone, it is recommended that the other antipsychotic be discontinued before starting risperidone therapy. Some patients may benefit from gradual discontinuation of the other antipsychotic; minimize the period of overlap between the other antipsychotic and oral risperidone.

Cognitive and motor impairment

Caution patients about operating potentially hazardous machinery (eg, cars) until they know whether the drug impairs their ability. Avoid use of alcohol.

Hyperglycemia and diabetes mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, may occur.

Hyperprolactinemia

May elevate prolactin levels.

Long-term use (more than 8 wk)

Long-term use not well evaluated. Periodically reevaluate usefulness.

Neuroleptic malignant syndrome (NMS)

NMS has occurred with antipsychotics and is potentially fatal. Signs and symptoms are altered mental status, cardiac dysrhythmia, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, and tachycardia.

Orthostatic hypotension

Orthostatic hypotension, associated with dizziness, syncope, and tachycardia, may occur.

Phenylketonurics

The orally disintegrating tablet contains phenylalanine.

Priapism

Other drugs with alpha-adrenergic properties have been reported to cause priapism. Reports with risperidone are rare and a casual relationship has not been established. No cases have been reported with IM risperidone.

Seizures

Seizures may occur. Use with caution in patients with a history of seizures.

Suicide

Possible suicide attempts are inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients. Write prescriptions for the smallest quantity consistent with good patient management.

Tardive dyskinesia

A potentially irreversible syndrome of involuntary body and facial movements may occur.

Overdosage

Symptoms

Cardiopulmonary arrest, convulsions, drowsiness, extrapyramidal symptoms, hypokalemia, hyponatremia, hypotension, prolonged QT and widened QRS intervals, tachycardia, torsades de pointes, seizures.

Patient Information

• Instruct patient to take prescribed dose once or twice daily as prescribed, without regard to meals. Advise patient to take with food if GI upset occurs.
• Advise patient receiving risperidone injection that medication will be prepared and administered by a health care provider in a medical setting.
• Instruct patient using oral solution to use calibrated pipette to measure each dose. Advise patient that solution may be mixed with 3 to 4 oz of water, coffee, orange juice, or low-fat milk (but not with cola or tea) prior to administration.
• Caution patient using disintegrating tablet not to open the blister until ready to take the dose.
• Advise patient that if a dose is missed to take it as soon as possible and then return to the normal schedule. However, if it is almost time for the next dose, to skip the missed dose and take the next dose at the regularly scheduled time. Instruct patient not to double the dose to catch up.
• Advise patient that dose will be started low and then increased until max benefit is obtained.
• Instruct patient not to change the dose or stop taking the medicine unless advised by health care provider.
• Instruct patient not to stop taking risperidone when feeling better.
• Tell patient to immediately report high fever, muscle rigidity, altered mental status, irregular pulse, sweating, seizures, or rash to health care provider.
• Instruct patient to contact health care provider if symptoms do not appear to improve or they worsen.
• Advise patient to notify health care provider of the following: excessive drowsiness, weight gain, involuntary body or facial movements, changes in personality or mood, frequent urination, excessive thirst.
• Advise patient to avoid strenuous activity during periods of high temperature or humidity.
• Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
• Instruct patient to avoid alcoholic beverages and sedatives (eg, diazepam) while taking risperidone.
• Instruct patient to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may make dizziness worse.
• Advise patient taking antihypertensives to monitor BP at regular intervals.
• Advise patient that drug may impair judgment, thinking, or motor skills, or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise phenylketonuric patients that orally disintegrating tablet contains phenylalanine.
• Advise patient that medication may cause photosensitivity and to use sunscreen or wear protective clothing until tolerance to the sun/UV light is determined.

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