Class: Benzisoxazole antipsychotic
- Tablets, oral 0.25 mg
- Tablets, oral 0.5 mg
- Tablets, oral 1 mg
- Tablets, oral 2 mg
- Tablets, oral 3 mg
- Tablets, oral 4 mg
- Solution, oral 1 mg/mL
- Injection, powder for suspension, ER 12.5 mg
- Injection, powder for suspension, ER 25 mg
- Injection, powder for suspension, ER 37.5 mg
- Injection, powder for suspension, ER 50 mg
- 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
- Tablets, orally disintegrating 0.25 mg
CO Risperidone (Canada)
Sandoz Risperidone (Canada)
Has antipsychotic effect, apparently caused by dopamine- and serotonin-receptor blocking in CNS.
Absolute oral bioavailability is 70%. T max is 1 h (risperidone), 3 h (9-hydroxyrisperidone extensive metabolizers), or 17 h (9-hydroxyrisperidone poor metabolizers). Steady state is approximately 1 day (extensive metabolizers) or approximately 5 days (poor metabolizers).IM
The main release of the drug starts 3 wk after injection, is maintained from 4 to 6 wk, and subsides by 7 wk. Steady state is reached after 4 injections.
Rapidly distributed. Vd is 1 to 2 L/kg. Protein binding is approximately 90% (parent compound) or approximately 77% (9-hydroxyrisperidone).
Extensively metabolized in the liver by CYP2D6 to major active metabolite 9-hydroxyrisperidone. 9-hydroxyrisperidone has similar activity to risperidone.
Eliminated in urine (70%) and feces (14%).PO
The half-life 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 half-life) for combined risperidone and 9-hydroxyrisperidone.IM
The half-life of risperidone plus 9-hydroxyrisperidone is 3 to 6 days. The Cl of risperidone and risperidone plus 9-hydroxyrisperidone is 13.7 and 5 L/h for extensive metabolizers and 3.3 and 3.2 L/h for poor metabolizers, respectively.
Special PopulationsRenal 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 approximately 35%. Dosage reduction recommended.Elderly
Renal Cl of parent drug and active metabolite was decreased. Elimination half-life was prolonged. Modify dose accordingly.IM
No dosing changes required.Children
Pharmacokinetics of risperidone and 9-hydroxyrisperidone in children were similar to those in adults.Gender
No pharmacokinetic differences identified.Race
No pharmacokinetic differences identified.
Indications and UsagePO
Acute and maintenance treatment of schizophrenia in adults; treatment of schizophrenia in adolescents 13 to 17 y of age; as monotherapy in short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents 10 to 17 y of age; as adjunct therapy to lithium or valproate for the short-term treatment of adults with acute manic or mixed episodes associated with bipolar I disorder; treatment of irritability associated with autistic disorder in pediatric patients 5 to 16 y of age.IM
Treatment of schizophrenia; as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder.
Treatment of patients with obsessive-compulsive disorder refractory to SSRIs, stuttering, tardive dyskinesia, Tourette syndrome, or chronic tic disorder (oral).
Hypersensitivity to risperidone or to any components of the product.
Dosage and AdministrationBipolar Mania
2 to 3 mg/day once daily initially. Adjust dose at intervals of no less than 24 h, in increments/decrements of 1 mg/day (usual dosage, 1 to 6 mg/day). No data to support short-term treatment beyond 3 wk.IM
25 mg every 2 wk. Some patients may benefit from a higher dose of 37.5 or 50 mg. Do not make upward dosage adjustments more frequently than every 4 wk.Pediatric patients 10 to 17 y of age
PO Start with 0.5 mg once daily. If indicated, dosage adjustments should occur at intervals of no less than 24 h and in increments of 0.5 or 1 mg/day, as tolerated, to a recommended dosage of 2.5 mg/day (dose range, 0.5 to 6 mg/day). Patients experiencing persistent somnolence may benefit from administering half the dose twice daily. No data to support treatment beyond 3 wk.Irritability Associated With Autistic Disorder
Pediatric patients 5 to 16 y of age
PO Can be administered once daily or half the total daily dose twice daily. Use caution with dosage for children weighing less than 15 kg. For patients less than 20 kg, the initial dosage is 0.25 mg/day. After a minimum of 4 days, the dosage may be increased to 0.5 mg/day. Maintain this dose for a minimum of 14 days. If sufficient clinical response is not obtained, the dosage 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 dosage is 0.5 mg/day. After a minimum of 4 days, the dosage may be increased to 1 mg/day. Maintain this dose for a minimum of 14 days. If sufficient clinical response is not obtained, the dosage may be increased in increments of 0.5 mg/day at intervals of no less than 14 days. Patients experiencing persistent somnolence may benefit from administering half the dose twice daily.Schizophrenia
Initial dosage is 2 mg/day administered once or twice daily. Dosage increases should occur at intervals of no less than 24 h, in increments of 1 to 2 mg/day as tolerated, to a recommended dosage of 4 to 8 mg/day (dose range, 4 to 16 mg/day). Periodically assess patients to determine the need for maintenance treatment with an appropriate dose.IM
25 mg every 2 wk (max, 50 mg every 2 wk). Do not make upward dosage adjustments more frequently than every 4 wk.Adolescents (13 to 17 y of age)
PO Initiate treatment with 0.5 mg once daily as a single dose in the morning or evening. If indicated, dosage adjustments should be at intervals of no less than 24 h, in increments of 0.5 to 1 mg/day, as tolerated, to a recommended dosage of 3 mg/day (dose range, 1 to 6 mg/day). Patients experiencing persistent somnolence may benefit from administering half the dose twice daily.Special Populations
Elderly patients and patients with renal or hepatic impairment who can tolerate at least 2 mg of oral risperidone
IM 25 mg every 2 wk. Alternatively, a starting dose of 12.5 mg may be appropriate in patients with renal or hepatic impairment.Elderly or debilitated patients, patients with severe renal or hepatic 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. In some patients, slower titration may be medically appropriate.
- When coadministered with enzyme inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin) or inhibitors (eg, fluoxetine, paroxetine), the risperidone dose needs to be titrated, especially during initiation or discontinuation of therapy.
- It is recommended that after an interval off risperidone, the initial titration schedule be followed.
- Administer by deep IM deltoid or gluteal injection only. For deltoid administration, use the 1-inch needle, alternating injections between the 2 arms. For gluteal administration, use the 2-inch needle, alternating between the 2 buttocks.
- For patients who have never taken oral risperidone, it is recommended to establish tolerability with oral risperidone prior to initiating treatment with risperidone injection.
- Oral risperidone (or another antipsychotic medication) should be given with the first injection of risperidone and should be continued for 3 wk to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site.
- Do not combine 2 different dosage strengths of risperidone in a single administration.
- Allow dose pack from refrigerator to reach room temperature before reconstituting powder for injection.
- Reconstitute powder for injection following manufacturer's guidelines and use the 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.
- When switching schizophrenic patients from depot antipsychotics, initiate risperidone therapy in place of the next scheduled injection.
- Oral solution
- Administer directly from calibrated pipette or mix with a beverage (ie, water, coffee, orange juice, low-fat milk) prior to administration. Do not mix with cola or tea.
- 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.
- Instruct patients to not split or chew tablet.
- Administer without regard to food.
Store tablets, orally disintegrating tablets, and oral solution at 59° to 77°F. Protect tablets from light and moisture. Protect oral solution from freezing. Store injection dose pack in refrigerator (36° to 46°F). Protect from light. 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 InteractionsAntihypertensives (eg, propranolol)
Risperidone may enhance hypotensive effects of some antihypertensives. Use caution and monitor the clinical response. Adjust the dose of the antihypertensive agent as needed.Cimetidine, ranitidine
May increase bioavailability of risperidone.Abiraterone, antipsychotics (eg, haloperidol, lithium, thioridazine), clozapine, CYP2D6 inhibitors (eg, fluoxetine, paroxetine), protease inhibitors (eg, indinavir, ritonavir)
Risperidone plasma levels may be elevated, increasing the therapeutic effects and adverse reactions. Monitor the clinical response to risperidone after starting or stopping one of these agents. In addition, monitor for adverse reactions (eg, serotonin syndrome) when these agents are coadministered. Adjust the risperidone dose as needed. Avoid coadministration with abiraterone.CNS depressants (eg, alcohol, tramadol)
Use with caution when risperidone is given with other centrally acting drugs. Avoid coadministration with alcohol.CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin)
Risperidone plasma levels may be reduced, decreasing the efficacy. If this combination cannot be avoided, monitor closely and adjust the dose of risperidone as needed.Gingko biloba
The risk of risperidone-induced priapism may be increased. If possible, avoid concurrent use.Levodopa and other dopamine agonists
Risperidone may antagonize the effects of levodopa and other dopamine agonists. Use with caution. Monitor the clinical response and adjust therapy as needed.Maprotiline, valproate
C max may be increased by risperidone. Observe the clinical response to these agents when starting, stopping, or changing the dose of risperidone. Adjust the dose of these agents as needed. Additionally, fluid retention with edema has been reported with concurrent use.QT-prolonging drugs
An additive effect of risperidone with other drugs that prolong the QT interval cannot be excluded. The following drugs may prolong the QT interval and increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes: antiarrhythmic agents (eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol), arsenic trioxide, chlorpromazine, cisapride, dolasetron, droperidol, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, tacrolimus, thioridazine, and ziprasidone.Topiramate
Coadministration decreased risperidone C max and AUC 23% and 33%, respectively.Verapamil
Risperidone plasma concentrations may be increased. Observe the clinical response to risperidone when starting, stopping, or changing the dose of verapamil. Adjust the risperidone dose as needed.
Tachycardia (5%); abnormal ECG, AV block, bundle branch block, cerebral ischemia, cerebrovascular accident, cerebrovascular disorder, decreased BP, flushing, sinus bradycardia, sinus tachycardia, transient ischemic attack (less than 5%); bradycardia, orthostatic hypotension, palpitation, QT prolongation (less than 4%); hypertension (3%); syncope (2%); atrial fibrillation, cardiopulmonary arrest (postmarketing).
Somnolence (49%); fatigue (42%); extrapyramidal symptoms (35%); insomnia (32%); sedation (29%); parkinsonism (28%); tremor (24%); headache (21%); anxiety, dizziness (16%); akathisia (11%); dyskinesia (7%); dystonia (6%); lethargy (5%); abnormal coordination, agitation, anorgasmia, balance disorder, blunted affect, confusional state, decreased libido, depressed level of consciousness, disturbance in attention, dysarthria, gait disturbance, hypersomnia, hypoesthesia, listlessness, loss of consciousness, malaise, middle insomnia, movement disorder, NMS, sleep disorder, speech disorder, tardive dyskinesia, unresponsive to stimuli (less than 5%); akinesia, convulsion, depression, hypokinesia, initial insomnia, nervousness, paresthesia, postural dizziness, vertigo (less than 4%); asthenia (2%); mania (postmarketing).
Rash (11%); acarodermatitis, erythema, erythematous rash, maculopapular rash, onychomycosis, papular rash, pruritus, skin discoloration, skin disorder, skin lesion (less than 5%); eczema, subcutaneous abscess (less than 4%); dry skin (3%); acne (2%); dandruff, hyperkeratosis, seborrheic dermatitis (1%); alopecia (postmarketing).
Nasopharyngitis (21%); rhinorrhea (16%); nasal congestion, rhinitis (13%); pharyngolaryngeal pain (10%); blurred vision (7%); chronic otitis media, conjunctivitis, decreased visual acuity, dry eye, dysphonia, ear infection, eye discharge, eye infection, eye rolling, eye swelling, eyelid edema, eyelid margin crusting, glaucoma, increased lacrimation, ocular hyperemia, otitis media, pharyngitis, photophobia, tinnitus, tonsillitis (less than 5%); ear pain (less than 4%); retinal artery occlusion (postmarketing).
Increased appetite (47%); vomiting (25%); constipation (21%); drooling, nausea, upper abdominal pain (16%); dry mouth (15%); dyspepsia (10%); diarrhea (8%); decreased appetite, stomach discomfort (6%); aptyalism, cheilitis, dysphagia, fecal incontinence, fecaloma, gastritis, lip swelling (less than 5%); abdominal pain, gastroenteritis (less than 4%); toothache (3%); abdominal pain (1%); intestinal obstruction, pancreatitis (postmarketing).
Amenorrhea, breast enlargement, cystitis, dysuria, ejaculation disorder, enuresis, erectile dysfunction, gynecomastia, irregular menstruation, pollakiuria, retrograde ejaculation, sexual dysfunction, vaginal discharge (less than 5%); breast discomfort, delayed ejaculation, delayed menstruation, galactorrhea, menstrual disorder, oligomenorrhea, urinary incontinence (less than 4%); UTI (3%); ejaculation failure (1%); precocious puberty, priapism, urinary retention (postmarketing).
Decreased Hct, decreased Hgb, decreased WBC, granulocytopenia, increased eosinophil count (less than 5%); anemia, neutropenia (less than 4%); agranulocytosis, thrombocytopenia (postmarketing).
Increased ALT, increased transaminases (less than 5%); increased AST, increased GGT, increased hepatic enzymes (less than 4%); jaundice (postmarketing).
Increased blood glucose, increase prolactin (less than 5%); glucose in urine (less than 4%); increased blood creatine phosphokinase (2%).
Injection-site induration, pain, swelling (less than 4%); injection-site redness (1%); injection-site reactions including abscess, cellulitis, cyst, hematoma, necrosis, nodule, or ulcer (postmarketing).
Weight gain (18%); anorexia, diabetic coma, face edema, generalized edema, peripheral edema, pitting edema, polydipsia, thirst (less than 5%); weight decreased (4%); hyperglycemia (less than 4%); diabetes mellitus, diabetic ketoacidosis, hypoglycemia, SIADH, water intoxication (postmarketing).
Pain in extremity (6%); abnormal posture, joint swelling, muscle weakness, musculoskeletal chest pain, myalgia, neck pain, rhabdomyolysis (less than 5%); back pain (4%); buttock pain (less than 4%); arthralgia (3%); joint stiffness (1%).
Coughing (24%); upper respiratory tract infection (8%); aspiration pneumonia, bronchitis, bronchopneumonia, hyperventilation, nasal edema, pneumonia, productive cough, pulmonary congestion, rales, respiratory disorder, respiratory tract congestion, respiratory tract infection, sinus congestion, tracheobronchitis, wheezing (less than 5%); dyspnea, lower respiratory tract infection, sinusitis (less than 4%); epistaxis (2%); pulmonary embolism, sleep apnea (postmarketing).
Feeling abnormal (5%); cellulitis, chest discomfort, chills, decreased body temperature, discomfort, drug hypersensitivity, drug withdrawal syndrome, hyperprolactinemia, increased body temperature, infection, influenza, influenza-like illness, peripheral coldness, sluggishness, viral infection (less than 5%); pain (4%); chest pain, fall, induration, hypersensitivity, procedural pain (less than 4%); pyrexia (2%); anaphylactic reaction, angioedema, hypothermia, pituitary adenomas, sudden death (postmarketing).
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Over the course of a 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. 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.
Regularly monitor patients with an established diagnosis of diabetes mellitus for worsening of glucose control. Perform fasting blood glucose testing at the beginning of treatment and periodically during treatment of patients with risk factors for diabetes mellitus (eg, family history of diabetes, obesity). Monitor any patient treated with atypical antipsychotics for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Perform fasting blood glucose testing on patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics. Consider monitoring of orthostatic vital signs in patients predisposed to hypotension (eg, CV disease, cerebrovascular disease, dehydration, hypovolemia, elderly patients, renal/hepatic impairment). Monitor renal function. If a patient requires risperidone treatment after recovery from NMS, carefully monitor the patient because recurrences of NMS have been reported. Frequently monitor CBC during the first few months of therapy in patients with a history of a clinically significant low WBC or drug-induced leukopenia/neutropenia. Carefully monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection. Monitor weight gain and growth in children.
Category C . Neonates exposed to antipsychotic drugs during the third trimester are at risk of extrapyramidal and/or withdrawal symptoms following delivery.
Excreted in breast milk. Women receiving risperidone should not breast-feed.
Safety and efficacy of IM risperidone in children not established.Autistic disorder
Safety and efficacy not established in children younger than 5 y.Bipolar disorder
Safety and efficacy not established in children younger than 10 y.Schizophrenia
Safety and efficacy not established in children younger than 13 y.
Elderly and debilitated patients may have reduced ability to eliminate risperidone. There is an increased risk of tardive dyskinesia, especially in elderly women. Cerebrovascular adverse reactions and fatalities may occur. Dosage adjustment required.
Hypersensitivity reactions, including anaphylactic reactions and angioedema, have occurred.
May experience enhanced effects of risperidone because of reduced ability to eliminate risperidone. Dose adjustment required.
May experience enhanced effects of risperidone because of decreased protein binding. Dose adjustment 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.
This effect may mask signs and symptoms of overdosage with certain drugs or conditions, such as intestinal obstruction.
Antipsychotics have been associated with esophageal dysmotility and aspiration. Use with caution in patients at risk of aspiration pneumonia.
Body temperature regulation
Antipsychotics can disrupt the body's ability to reduce core temperature.
Cerebrovascular events (eg, stroke, transient ischemic attack), including fatalities, may occur, especially in elderly patients.
Cognitive and motor performance
Judgment, thinking, or motor skills may be impaired.
Leukopenia/neutropenia and agranulocytosis have occurred.
Hyperglycemia and diabetes mellitus
Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, may occur.
May elevate prolactin levels.
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, associated with dizziness, syncope, and tachycardia, may occur, especially during the initial dose-titration period.
The orally disintegrating tablet contains phenylalanine.
Priapism may occur, and severe cases may require surgical intervention.
Seizures may occur. Use with caution in patients with a history of seizures.
Possible suicide attempts are inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients. Prescribe the smallest quantity consistent with good patient management.
A potentially irreversible syndrome of involuntary body and facial movements may occur.
Thrombotic thrombocytopenia purpura
Has occurred in 1 patient; relationship to risperidone is unknown.
Convulsions, drowsiness, extrapyramidal symptoms, hypokalemia, hyponatremia, hypotension, prolonged QT and widened QRS intervals, sedation, tachycardia, torsades de pointes.
- 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 90 to 120 mL of water, coffee, orange juice, or low-fat milk (but not cola or tea) prior to administration.
- Caution patient using orally disintegrating tablet not to open the blister until they are ready to take the dose.
- Advise patient that dose will be started low and then increased until maximum benefit is obtained.
- Instruct patient not to stop taking risperidone when feeling better.
- Tell patient to immediately report altered mental status, high fever, irregular pulse, muscle rigidity, rash, seizures, or sweating to health care provider.
- Instruct patient to contact health care provider if symptoms do not appear to improve or if they worsen.
- Advise patient to notify health care provider of the following: changes in personality or mood, excessive drowsiness, excessive thirst, frequent urination, involuntary body or facial movements, weight gain.
- 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 patients to notify their health care provider if they become pregnant or intend to become pregnant during therapy and for at least 12 wk after last injection of risperidone.
- Advise breast-feeding women not to breast-feed during therapy and for at least 12 wk after last injection of risperidone.
- 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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