risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)
Dosing and uses of Risperdal, Risperdal Consta (risperidone)
Adult dosage forms and strengths
tablet
- 0.25mg
- 0.5mg
- 1mg
- 2mg
- 3mg
- 4mg
tablet, orally disintegrating
- 0.25mg
- 0.5mg
- 1mg
- 2mg
- 3mg
- 4mg
oral solution
- 1mg/mL
powder for injection
- 12.5mg
- 25mg
- 37.5mg
- 50mg
Schizophrenia
PO
- 2 mg/day initially; may be increased in increments of 1-2 mg/day at intervals ≥24 hours
- Recommended target dosage: 2-8 mg/day once daily or divided q12hr (efficacy follows bell-shaped curve; 4-8 mg/day more effective than 12-16 mg/day)
Im
- 12.5-50 mg injected into deltoid or gluteal muscle every 2 weeks; dosage should not be adjusted more frequently than every 4 weeks
- Recommended to establish tolerability of PO risperidone before initiating treatment with IM risperidone
Bipolar Mania
PO
- 2-3 mg/day initially; may be increased if necessary in increments of 1 mg/day at intervals of 24 hours to 6 mg/day; dosage recommendations not available for treatment duration >3 weeks
Im
- 12.5-50 mg injected into deltoid or gluteal muscle every 2 weeks; dosage should not be adjusted more frequently than every 4 weeks
- Recommended to establish tolerability of PO risperidone before initiating treatment with IM risperidone
Tourette Syndrome (Off-label)
0.5-1 mg/day PO; may be increased or decreased in increments of 0.5 mg q12hr at intervals >3 days; not to exceed 6 mg/day
Posttraumatic Stress Disorder (Off-label)
0.5-8 mg/day PO
Administration
IM Administration
- Use supplied diluent for resuspension only
- Administer within 2 minutes of resuspension; if this is not done, shake vigorously to resuspend
Dosing Modifications
Renal impairment
- CrCl < 30 mL/min
- PO: 0.5 mg q12hr initially; consider longer titration intervals; may be increased by up to 0.5 mg/day PO divided q12hr; dosage increase >1.5 mg q12hr should occur no more frequently than once weekly
- IM: If 2-mg total daily dose of PO resperidone is well tolerated, may start with 12.5-25 mg IM every 2 weeks; continue PO supplementation for 3 weeks after first injection until main release of risperidone from injection has begun
Hepatic impairment
- PO: 0.5 mg q12hr initially; consider longer titration intervals; may be increased by up to 0.5 mg/day PO divided q12hr; dosage increase >1.5 mg q12hr should occur no more frequently than once weekly
- IM: If 2-mg total daily dose of PO resperidone is well tolerated, may start with 25 mg IM every 2 weeks; continue PO supplementation for 3 weeks after first injection until main release of risperidone from injection has begun
Pediatric dosage forms and strengths
tablet
- 0.25mg
- 0.5mg
- 1mg
- 2mg
- 3mg
- 4mg
tablet, orally disintegrating
- 0.25mg
- 0.5mg
- 1mg
- 2mg
- 3mg
- 4mg
oral solution
- 1mg/mL
Schizophrenia
<13 years: Safety and efficacy not established
>13 years: 0.5 mg/day PO in morning or evening initially; may be increased in increments of 0.5-1 mg/day at intervals ≥24 hr to recommended dosage of 3 mg/day; dosage range: 1-6 mg/day (dosages >3 mg/day have not been proved more effective and are associated with increased incidence of adverse effects)
If persistent somnolence occurs, daily dose may be divided q12hr
Bipolar Mania
<10 years: Safety and efficacy not established
>10 years: 0.5 mg/day PO in morning or evening initially; may be increased in increments of 0.5-1 mg/day at intervals ≥24 hr to recommended dosage of 2.5 mg/day; dosage range: 0.5-6 mg/day (dosages >2.5 mg/day have not been proved more effective and are associated with increased incidence of adverse effects)
If persistent somnolence occurs, daily dose may be divided q12hr
Autism
Irritability associated with autistic disorder in children aged 5-16 years
<5 years: Safety and efficacy not established
5-16 years (<20 kg): 0.25 mg/day PO initially; may be increased after ≥4 days to recommended dosage of 0.5 mg/day
5-16 years (≥20 kg): 0.5 mg/day PO initially; may be increased after ≥4 days to recommended dosage of 1 mg/day
Insufficient response to recommended dosage
- If response to recommended dosage insufficient, dosage may be adjusted as follows after minimum of 14 days and at least every 2 weeks thereafter
- <20 kg: Adjusted in increments of 0.25 mg/day; not to exceed 1 mg/day
- ≥20 kg: Adjusted in increments of 0.5 mg/day; not to exceed 2.5 mg/day
Geriatric dosage forms and strengths
Not approved for dementia-related psychosis, because of increased risk of cardiovascular or infectious related deaths (see Black box warnings)
Risk of orthostatic hypotension higher in elderly; monitoring of renal function and orthostatic blood pressure may be necessary; for titrating to target dose, twice-daily regimen should be used and dosage maintained for 2-3 days before change is made to once-daily dose regimen
Schizophrenia, Bipolar Mania
Use lower initial dose, and adjust more gradually
PO: 0.5 mg q12hr; may be increased in increments ≤0.5 mg q12hr; increases to dosages >1.5 mg q12hr should occur at intervals ≥1 week
IM: 12.5-25 mg injected into deltoid or gluteal muscle every 2 weeks; dosage should not be adjusted more frequently than every 4 weeks
Recommended to establish tolerability of PO risperidone before initiating treatment with IM risperidone
Psychosis, Agitation Related to Alzheimer Dementia (Off-label)
0.25-1 mg/day PO initially; may be increased gradually as tolerated; not to exceed 1.5-2 mg/day
Risperdal, Risperdal Consta (risperidone) adverse (side) effects
>10%
Somnolence (40-45%)
Insomnia (26-30%)
Agitation (20-25%)
Anxiety (10-15%)
Headache (10-15%)
Rhinitis (10-15%)
Fatigue (18-31%)
Parkinsonism (28-62%)
Akathisia (5-11%)
Increased appetite (4-44%)
Vomiting (10-20%)
Drooling (<12%)
Urinary incontinence (5-22%)
Tremor (11-24%)
Nasopharyngitis (4-19%)
Rhinorrhea (4-12%)
Enuresis (1-16%)
1-10%
Constipation (5-10%)
Dyspepsia (5-10%)
Nausea (5-10%)
Abdominal pain (1-5%)
Aggressive reaction (1-5%)
Facial edema (<4%)
QT prolongation (<4%)
Dizziness (1-5%)
Extrapyramidal symptoms (EPS; 1-5%)
Gynecomastia in children (1-5%)
Rash (1-5%)
Tachycardia (1-5%)
Syncope (1-2%)
Bradycardia (<4%)
Palpitation (<4%)
Chest pain (<4%)
Agitation (<4%)
Postural dizziness (<4%)
Pruritus (<4%)
Acne (1-2%)
Hyperprolactinemia (<4%)
Sexual dysfunction (<4%)
Xerostomia (7-10%)
<1%
Agranulocytosis
Cholesterol increased
Delirium
Ketoacidosis
Orthostatic hypotension
Seizures
Frequency not defined
Diabetes mellitus
Hyperthermia
Hypoglycemia
Hypothermia
Myelosuppression
Neuroleptic malignant syndrome (NMS)
Priapism
Prolonged QT intervaL
Tardive dyskinesia
Thrombotic thrombocytopenic purpura (TTP)
Sleep apnea syndrome
Urinary retention
Warnings
Black box warnings
Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths in these trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
Contraindications
Documented hypersensitivity
Cautions
Increased incidence of cerebrovascular disease reported; may alter cardiac conduction; life threatening arrhythmias reported with therapeutic doses of antipsychotics
May cause anicholinergic effects including blurred vision, urinary retention, agitation, confusion, blurred vision, and xerostomia
Use with caution in patients with history of seizures, Parkinson disease, Lewy body dementia, cardiovascular disease, hypovolemia, dehydration
Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia
If patient has history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/μL in absence of other causative factors, and continue monitoring WBC count until recovery
Use caution in patients at risk of pneumonia; esophageal dysmotility and aspiration reported with antipsychotic use
May cause extrapyramidal symptoms including acute dystonic reactions, akathisia, pseudoparkinsonism, and tardive dyskinesia
Intraoperative floppy iris syndrome reported in patients receiving risperidone therapy
Monitor for fever, mental status changes, muscle regidity and or autonomic instability; neuroleptic malignant syndrome associated with resperidone use
Use with caution in children <15 kg
Cases of priapism reported with therapy
Prolactin elevations occur and persist during chronic administration
Use caution when operating heavy machinery
Risk of orthostatic hypotension
FDA warning regarding off-label use for dementia in elderly
Metabolic changes
- Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk (eg, hyperglycemia, dyslipidemia, and body weight gain)
- In some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death
Pregnancy and lactation
Pregnancy category: C
Neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for EPS or withdrawal symptoms after delivery; these complications vary in severity, with some being self-limited and others requiring ICU support and prolonged hospitalization
Lactation: Drug distributed in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Risperdal, Risperdal Consta (risperidone)
Mechanism of action
Improves negative symptoms of psychoses and reduces incidence of EPs
Has high affinity for serotonin type 2 (5-HT2) receptors; binds to dopamine D2 receptors with 20 times lower affinity than that for 5-HT2 receptors; antagonizes alpha1-adrenergic, alpha2-adrenergic, and histaminergic receptors; has moderate affinity for serotonin type 1 (5-HT1C, 5-HT1D, 5-HT1A) receptors; has weak affinity for dopamine D1 receptors; has no affinity for muscarinic, beta1-adrenergic, and beta2-adrenergic receptors
Absorption
Bioavailability: 70%
Peak plasma time: Extensive metabolizers, 3 hr; poor metabolizers, 17 hr
Distribution
Protein bound: Risperidone, 90%; metabolite, 77%
Vd: 1-2 L/kg
Metabolism
Metabolized in liver by CYP2D6
Metabolite: 9-hydroxyrisperidone (paliperidone)
Elimination
Half-life: Extensive metabolizers, 3 hr (parent and metabolite combined); poor metabolizers, 20 hr (parent and metabolite combined); prolonged in renal impairment; free fraction increase in hepatic disease
Excretion: Urine (70%), feces (14%)