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- 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
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 mgApo-Risperidone (Canada)CO Risperidone (Canada)Gen-Risperidone (Canada)Novo-Risperidone (Canada)PMS-Risperidone (Canada)ratio-Risperidone (Canada)Sandoz Risperidone (Canada)
Has antipsychotic effect, apparently caused by dopamine- and serotonin-receptor blocking in CNS.
PO 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 about 1 day (extensive metabolizers) or about 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 about 90% (parent compound) or about 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, respectively, for extensive metabolizers and 3.3 and 3.2 L/h, respectively, for poor metabolizers.
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 half-life was prolonged. Modify dose accordingly. IM No dosing changes required.Gender
No pharmacokinetic differences identified.Race
No pharmacokinetic differences identified.
PO Acute and maintenance treatment of schizophrenia; short-term treatment of acute manic or mixed episodes associated with bipolar I disorder as monotherapy or as adjunct therapy to lithium or valproate; treatment of irritability associated with autistic disorder.
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, Tourette syndrome, or chronic tic disorder (oral).
PO 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 (max, 6 mg/day). No data to support acute treatment beyond 3 wk. IM 25 mg every 2 wk (max, 50 mg every 2 wk).Children 10 to 17 yr of age
PO Administer once daily in the morning or evening. 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 (max, 6 mg/day). Patients experiencing persistent somnolence may benefit from administering half the dose twice daily. There are no data to support treatment beyond 3 wk.Irritability Associated With Autistic DisorderChildren 5 to 16 yr of age
PO Can be administered once daily or half the total daily dose twice daily. Use caution with dosages 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. Max daily dose is 1 mg. 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. Max daily dose is 2.5 mg for patients 20 to 45 kg and 3 mg for patients weighing more than 45 kg.SchizophreniaAdults
PO Can be administered once or twice daily. Initial dosage is 2 mg/day. 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 (max, 16 mg/day). Periodically assess patients to determine 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 yr of age)
PO Initiate treatment with 0.5 mg once daily as a single dose in 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 (max, 6 mg/day).Special PopulationsElderly 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, 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.
Store tablets, orally disintegrating tablets, and oral solution at 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). 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.
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.Inhibitors of CYP2D6 (eg, clozapine, SSRIs [eg, fluoxetine, paroxetine, sertraline], thioridazine) and other CYP isozymes (eg, indinavir, itraconazole, ketoconazole, ritonavir)
Risperidone plasma levels may be elevated, increasing the therapeutic effects and adverse reactions.Lamotrigine, verapamil
Risperidone plasma concentrations may be increased.Levodopa and other dopamine agonists
Risperidone may antagonize the effects of levodopa and other dopamine agonists.Maprotiline, valproate
Peak plasma levels may be increased by risperidone.QT prolongating 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, ziprasidone.
None well documented.
Tachycardia (7%); AV block, bundle branch block, cerebrovascular disorder (less than 5%); bradycardia (less than 4%); hypertension (3%); palpitation, postural hypotension, syncope (2%); arrhythmia, hypotension (1%); atrial fibrillation, cardiopulmonary arrest, cerebrovascular disorder, QT prolongation (postmarketing).
Somnolence (67%); fatigue (42%); extrapyramidal symptoms (31%); tremor (24%); headache (21%); parkinsonism (20%); dystonia (18%); anxiety, dizziness (16%); akathisia (11%); automatism, dyskinesia, sedation (7%); confusion (5%); abnormal gait, agitation, apathy, ataxia, coma, decreased libido, dysphonia, emotional lability, hypoesthesia, impaired concentration, impotence, insomnia, malaise, nervousness, NMS, speech disorder, stupor, tardive dyskinesia, vertigo (less than 5%); asthenia (1%); mania (postmarketing).
Rash (11%); erythema multiforme, erythematous rash, maculopapular rash, skin discoloration, skin exfoliation, skin ulceration (less than 5%); acne, dry skin, seborrhea (2%); alopecia (postmarketing).
Hyperprolactinemia (less than 5%).
Rhinitis (36%); abnormal vision (7%); pharyngitis (5%); conjunctivitis, otitis media (less than 5%); blurred vision (3%); earache (1%); retinal artery occlusion (postmarketing).
Increased appetite (49%); vomiting (25%); increased salivation (22%); constipation (21%); abdominal pain (18%); dyspepsia, nausea (16%); dry mouth (13%); anorexia, diarrhea (8%); decreased appetite (6%); dysphagia, flatulence (less than 5%); toothache (3%); intestinal obstruction, pancreatitis (postmarketing).
Urinary incontinence (22%); lactation nonpuerperal (5%); abnormal sexual function, amenorrhea, ejaculation disorder, gynecomastia, leukorrhea, menstrual disorder, micturition frequency, priapism (less than 5%); UTI (3%); ejaculation failure (1%); precocious puberty (postmarketing).
Granulocytopenia, leukopenia, purpura (less than 5%); epistaxis (2%); anemia (1%); agranulocytosis, thrombocytopenia (postmarketing).
Increased ALT, increased hepatic enzymes (less than 5%); jaundice (postmarketing).
Injection-site pain (at least 1%); injection-site reactions including abscess, cellulitis, cyst, hematoma necrosis, nodule, or ulcer (postmarketing).
Weight increase (5%); aggravated diabetes mellitus, diabetic coma, generalized edema, hyperglycemia, peripheral edema, thirst, xerophthalmia (less than 5%); weight decrease (4%); increased CPK (2%); diabetic ketoacidosis, SIADH, water intoxication (postmarketing).
Pain in extremity (6%); leg cramps, muscle weakness, rhabdomyolysis (less than 5%); arthralgia (4%); myalgia (less than 4%); back pain (3%).
Upper respiratory tract infection (34%); coughing (24%); dyspnea (5%); respiratory disorder (less than 5%); sinusitis (less than 4%); apnea, pulmonary embolism (postmarketing).
Fever (20%); abnormal crying, allergic reaction, allergy, allergy aggravated, anaphylactoid reaction, hypothermia, influenza-like symptoms, leg pain, pain, rigors, speech disorder, viral infection (less than 5%); chest pain (3%); angioedema, 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-wk 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 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. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug. Consider monitoring of orthostatic vital signs in patients predisposed to hypotension (eg, CV disease, cerebrovascular disease, dehydration, hypovolemia, elderly, renal/hepatic impairment). Monitor renal function in patients with renal impairment. If a patient requires risperidone treatment after recovery from NMS, carefully monitor the patient because recurrences of NMS have been reported.
Category C .
Excreted in breast milk.
Safety and efficacy of IM dose in children not established.Autistic disorder
Safety and efficacy not established in children younger than 5 yr of age.Bipolar disorder
Safety and efficacy not established in children younger than 10 yr of age.Schizophrenia
Safety and efficacy not established in children younger than 13 yr of age.
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. Dosage adjustment may be required.
May experience enhanced effects of risperidone because of reduced ability to eliminate risperidone. Dose adjustment may be required.
May experience enhanced effects of risperidone because of decreased protein binding. Dose adjustment may be required.
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 for aspiration pneumonia.
Antipsychotics can disrupt the body's ability to reduce core temperature.
Appears to have proarrhythmic effects.
Cerebrovascular adverse reactions (eg, stroke, transient ischemic attack), including fatalities, may occur, especially in elderly patients.
Judgment, thinking, or motor skills may be impaired.
Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma, or death, may occur.
May elevate prolactin levels.
Long-term use not well evaluated. Periodically reevaluate usefulness.
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.
The orally disintegrating tablet contains phenylalanine.
Other drugs with alpha-adrenergic properties have been reported to cause priapism. Reports with risperidone are rare and a causal relationship has not been established. No cases have been reported with IM risperidone.
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.
Has occurred in 1 patient; relationship to risperidone is unknown.
Cardiopulmonary arrest, convulsions, drowsiness, extrapyramidal symptoms, hypokalemia, hyponatremia, hypotension, prolonged QT and widened QRS intervals, sedation, tachycardia, torsades de pointes.
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