riss-PER-i-done

Therapeutic Classification: antipsychotics

Pharmacologic Classification: benzisoxazoles

• PO, IM, SC: Schizophrenia.
• PO: Acute manic or mixed episodes associated with bipolar I disorder (as monotherapy or in combination with lithium or valproate).
• IM: Maintenance treatment of bipolar I disorder (as monotherapy or in combination with lithium or valproate).
• PO: Irritability associated with autistic disorder.

• May act by antagonizing dopamine and serotonin in the CNS.

• Decreased symptoms of psychoses, bipolar mania, or autism.

Absorption: 70% after administration of tablets, solution, or orally disintegrating tablets. Following IM administration, small initial release of drug, followed by 3-wk lag; the rest of release starts at 3 wk and lasts 4–6 wk. Following SUBQ administration, initial release of drug occurs at 4–6 hr, with the rest of release occurring at 10–14 days after administration.

Distribution: Unknown.

Metabolism/Excretion: Primarily metabolized by the liver by the CYP2D6 isoenzyme to 9-hydroxyrisperidone (has similar pharmacological properties as risperidone). Risperidone and its active metabolite are renally eliminated.

Half-life: Extensive metabolizers: 3 hr for risperidone, 21 hr for 9-hydroxyrisperidone. Poor metabolizers: 20 hr for risperidone and 30 hr for 9-hydroxyrisperidone; SUBQ: 9–11 days.

(clinical effects)

†After discontinuation.

Contraindicated in:

• Hypersensitivity to risperidone or paliperidone
• Lactation: Lactation.

Use Cautiously in:

• Renal or hepatic impairment (initial dose ↓ recommended)
• Underlying cardiovascular disease (↑ risk of arrhythmias and hypotension)
• History of seizures
• History of drug abuse
• Diabetes or risk factors for diabetes (may worsen glucose control)
• Patients at risk for aspiration or falls
• Renal impairment
• Hepatic impairment
• OB: Neonates at ↑ risk for extrapyramidal symptoms and withdrawal after delivery when exposed during the 3rd trimester; use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Safety and effectiveness not established in children <13 yr (schizophrenia), <10 yr (bipolar disorder), or <5 yr (autism)
• Geri: Appears on Beers list. ↑ risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia or bipolar disorder.

CV: arrhythmias, orthostatic hypotension, syncope, tachycardia.

Derm: itching/skin rash, ↑ pigmentation, dry skin, photosensitivity, seborrhea, STEVENS-JOHNSON SYNDROME, sweating, TOXIC EPIDERMAL NECROLYSIS.

EENT: pharyngitis, rhinitis, visual disturbances.

Endo: galactorrhea, hyperglycemia.

F and E: polydipsia.

GI: constipation, diarrhea, dry mouth, nausea, ↑ salivation, abdominal pain, anorexia, dyspepsia, dysphagia, vomiting.

GU: ↓libido, dysmenorrhea/menorrhagia, ↓ fertility (females), amenorrhea, difficulty urinating, gynecomastia, impotence, polyuria, priapism.

Hemat: AGRANULOCYTOSIS, leukopenia, neutropenia.

Metab: weight gain, dyslipidemia, weight loss.

MS: arthralgia, back pain.

Neuro: ↑dreams, ↑sleep duration, aggressive behavior, dizziness, extrapyramidal reactions, headache, insomnia, sedation, fatigue, impaired temperature regulation, nervousness, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, tardive dyskinesia.

Resp: cough, dyspnea.
Misc: (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• May ↓ the antiparkinsonian effects of levodopa or other dopamine agonists.
• Strong CYP3A4 inducers, including carbamazepine, phenytoin, rifampin, and phenobarbital may ↑ metabolism and may ↓ effectiveness; dose adjustments may be necessary.
• Fluoxetine and paroxetine↑ blood levels and may ↑ effects; dose adjustments may be necessary.
• Clozapine↓ metabolism and may ↑ effects of risperidone.
• ↑CNS depression may occur with other CNS depressants, including alcohol, antihistamines, sedative/hypnotics, or opioid analgesics.
• Concurrent use with methylphenidate may ↑ risk of extrapyramidal symptoms.

Drug-Natural Products:

• Kava, valerian, or chamomile can ↑ CNS depression.

Schizophrenia

• PO (Adults): 1 mg twice daily, ↑ by 1–2 mg/day no more frequently than every 24 hr to 4–8 mg daily.
• PO (Children 13–17 yr): 0.5 mg once daily, ↑ by 0.5–1.0 mg no more frequently than every 24 hr to 3 mg daily. May administer half the daily dose twice daily if drowsiness persists.
• IM (Adults): 25 mg every 2 wk; some patients may benefit from a higher dose of 37.5 or 50 mg every 2 wk.
• IM (Geriatric Patients): 25 mg every 2 wk.
• SC (Adults): Currently taking (switching from) 2 mg/day of oral risperidone: Uzedy: 50 mg once monthly or 100 mg every 2 mo; Currently taking (switching from) 3 mg/day of oral risperidone: Perseris: 90 mg once monthly; Uzedy: 75 mg once monthly or 150 mg every 2 mo; Currently taking (switching from) 4 mg/day of oral risperidone: Perseris: 120 mg once monthly; Uzedy: 100 mg once monthly or 200 mg every 2 mo; Currently taking (switching from) 5 mg/day of oral risperidone: Uzedy: 125 mg once monthly or 250 mg every 2 mo; Concurrent use of strong CYP2D6 inhibitor (e.g., fluoxetine or paroxetine): Perseris: Initiate 90 mg once monthly 2–4 wk before starting strong CYP2D6 inhibitor therapy; Uzedy: When initiation of strong CYP2D6 inhibitor is expected, place patients on a lower dose of risperidone prior to the planned start of the strong CYP2D6 inhibitor. When a strong CYP2D6 inhibitor is initiated in patients already receiving the lowest risperidone dose (50 mg once monthly or 100 mg every 2 mo), continue treatment with these doses unless clinical judgment requires interruption of treatment. Concurrent use of strong CYP3A4 inducer: Perseris: If receiving 90 mg once monthly regimen, ↑ dose to 120 mg once monthly (and consider using additional oral risperidone); if receiving 120 mg once monthly regimen, consider using additional oral risperidone; Uzedy: Upon initiation of therapy with a strong CYP3A4 inducer, closely monitor patients during the first 4–8 wk since the dose of Uzedy may need to be adjusted. A dose ↑ of Uzedy or additional oral risperidone may be considered.

Acute Manic or Mixed Episodes Associated With Bipolar I Disorder

• PO (Adults): 2–3 mg/day as a single daily dose, dose may be ↑ at 24-hr intervals by 1 mg (range 1–5 mg/day).
• PO (Children 13–17 yr): 0.5 mg once daily, ↑ by 0.5–1 mg no more frequently than every 24 hr to 2.5 mg daily. May administer half the daily dose twice daily if drowsiness persists.
• PO (Geriatric Patients): Start with 0.5 mg twice daily; ↑ by 0.5 mg twice daily, up to 1.5 mg twice daily; then ↑ at weekly intervals if necessary. May also be given as a single daily dose after initial titration.

Maintenance Treatment of Bipolar I Disorder

• IM (Adults): 25 mg every 2 wk; some patients may benefit from a higher dose of 37.5 or 50 mg every 2 wk.
• IM (Geriatric Patients): 25 mg every 2 wk.

Irritability Associated With Autistic Disorder

• PO (Children 5–16 yr weighing <20 kg): 0.25 mg/day initially. After at least 4 days of therapy, may ↑ to 0.5 mg/day. Dose ↑ in increments of 0.25 mg/day may be considered at 2 wk or longer intervals. May be given as a single or divided dose.
• PO (Children 5–16 yr weighing >20 kg): 0.5 mg/day initially. After at least 4 days of therapy, may ↑ to 1 mg/day. Dose ↑ in increments of 0.5 mg/day may be considered at 2 wk or longer intervals. May be given as a single or divided dose.

(Generic available)

• Immediate-release tablets: 0.25 mg; 0.5 mg; 1 mg; 2 mg; 3 mg; 4 mg;
• Orally disintegrating tablets (Risperdal M-Tabs): 0.25 mg; 0.5 mg; 1 mg; 2 mg; 3 mg; 4 mg;
• Oral solution: 1 mg/mL;
• Extended-release suspension for IM injection (Risperdal Consta, Rykindo): 12.5 mg/vial kit; 25 mg/vial kit; 37.5 mg/vial kit; 50 mg/vial kit;
• Extended-release suspension for SUBQ injection (Perseris): 90 mg/vial kit; 120 mg/vial kit;
• Extended-release suspension for SUBQ injection (Uzedy): 50 mg/0.14 mL; 75 mg/0.14 mL; 100 mg/0.28 mL; 125 mg/0.35 mL; 150 mg/0.42 mL; 200 mg/0.56 mL; 250 mg/0.7 mL;

• Monitor patient’s mental status (orientation, mood, behavior) and mood before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression, especially during early therapy. Restrict amount of drug available to patient.
• Assess weight and BMI initially and throughout therapy. Monitor for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, weakness) periodically during therapy.
• Monitor BP (sitting, standing, lying down) and pulse before and frequently during initial dose titration. May cause prolonged QT interval, tachycardia, and orthostatic hypotension. If hypotension occurs, dose may need to be decreased.
• Observe patient when administering medication to ensure medication is swallowed and not hoarded or cheeked.
• Monitor patient for onset of extrapyramidal side effects (akathisia: restlessness; dystonia: muscle spasms and twisting motions; or pseudoparkinsonism: mask-like face, rigidity, tremors, drooling, shuffling gait, dysphagia). Report these symptoms; reduction of dose or discontinuation may be necessary. Trihexyphenidyl or benztropine may be used to control symptoms.
• Monitor for tardive dyskinesia (involuntary rhythmic movement of mouth, face, and extremities). Report immediately; may be irreversible.
• Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Notify health care professional immediately if these symptoms occur.
• Monitor for symptoms related to hyperprolactinemia (menstrual abnormalities, galactorrhea, sexual dysfunction).
• Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.
• Monitor weight during therapy. May cause weight gain in children and adolescents.
• Monitor for skin rash during therapy. May require discontinuation of therapy.

• May cause ↑ serum prolactin levels.
  • May cause ↑ AST and ALT.
  • May also cause anemia, thrombocytopenia, leukocytosis, and leukopenia.
  • Obtain fasting blood glucose and cholesterol levels initially and periodically during therapy.
  • Monitor CBC frequently during initial mo of therapy in patients with pre-existing or history of low WBC. May cause leukopenia, neutropenia, or agranulocytosis. Discontinue therapy if this occurs.
  • Monitor serum prolactin prior to and periodically during therapy. May cause ↑ serum prolactin levels.

• Do not confuse risperidone with ropinirole. Do not confuse Risperdal with Restoril or ropinirole.
  • When switching from other antipsychotics, discontinue previous agents when starting risperidone and minimize the period of overlapping antipsychotic agents.
  • If therapy is reinstituted after an interval off risperidone, follow initial titration schedule.
  • For IM use, establish tolerance with oral dosing before IM use and continue oral dosing for 3 wk following initial IM injection. Risperdal Consta: Take oral doses for 3 wk, starting with the 1st dose of risperidone. Then discontinue PO doses. Rykindo: Take oral doses for 7 days, starting with day of 1st dose of risperidone. After 7 days, discontinue PO doses. Do not increase dose more frequently than every 4 wk.
• PO: Daily doses can be taken in the morning or evening.
  • For orally disintegrating tablets, open blister pack by pealing back foil to expose tablet; do not try to push tablet through foil. Use dry hands to remove tablet from blister and immediately place entire tablet on tongue. Tablets disintegrate in mouth within sec and can be swallowed with or without liquid. Do not attempt to split or chew tablet. Do not try to store tablets once removed from blister.
  • Oral solution can be administered directly from calibrated oral dosing syringe or mixed with water, coffee, orange juice, or low-fat milk; do not mix with cola or tea.
• SC: Mix Perseris according to manufacturer's instructions. May be injected into abdomen or back of upper arm; avoid areas with nodules, lesions, excessive pigment, irritation, redness, bruising, infection, or scarring. Hold syringe upright for several sec to allow air bubbles to rise; depress the plunger to expel excess air. Pinch skin to avoid IM injection. Do not rub site after injection. Advise patient that they may have a lump for several wk; will decrease in size over time. Instruct patient not to rub or massage injection site and avoid constriction by belts or clothing waistbands.
• IM: Reconstitute with 2 mL of diluent provided by manufacturer. Administer via deep deltoid (1-in. needle) or gluteal (2-in. needle) injection using enclosed safety needle; alternate arms or buttocks with each injection. Allow solution to warm to room temperature prior to injection. Administer immediately after mixed with diluent; shake well to mix suspension. Must be administered within 6 hr of reconstitution. Store dose pack in refrigerator.
  • Do not combine dose strengths in a single injection.

• Instruct patient to take medication as directed.
• Inform patient of the possibility of extrapyramidal symptoms. Instruct patient to report these symptoms immediately to health care professional.
• Advise patient to change positions slowly to minimize orthostatic hypotension. Protect from falls.
• May cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking; other unusual changes in behavior or mood occur.
• Advise patient to use sunscreen and protective clothing when exposed to the sun to prevent photosensitivity reactions. Extremes in temperature should also be avoided; this drug impairs body temperature regulation.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Caution patient to avoid concurrent use of alcohol and other CNS depressants.
• Advise patient to notify health care professional of medication regimen before treatment or surgery.
• Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, tremors, or symptoms of hyperglycemia occur.
• May cause fetal harm. Advise females or reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding. Encourage women who become pregnant while taking risperidone to enroll in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit womensmentalhealth.org/research/pregnancyregistry/. Monitor neonates for extrapyramidal and/or withdrawal symptoms. Monitor infants exposed to risperidone through breast milk for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements). May impair fertility in females; usually reversible.
• Emphasize the importance of routine follow-up exams to monitor side effects and continued participation in psychotherapy to improve coping skills.

• Decrease in excited, manic behavior.
• Decrease in positive symptoms (delusions, hallucinations) of schizophrenia.
• Decreased aggression toward others, deliberate self-injury, temper tantrums, and mood changes in children with autism.
• Decrease in negative symptoms (social withdrawal, flat, blunted affects) of schizophrenia.
• Decrease in autism symptoms.

Perseris, RisperDAL, RisperDAL Consta, RisperDAL M-TAB, Rykindo, Uzedy