risperidone (Risperdal, Risperdal Consta, Risperdal M-Tab)

Dosing and uses of Risperdal, Risperdal Consta (risperidone)

• Adult
• Pediatric
• Geriatric

 

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%)