Risperidone Odt (risperidone)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Risperidone, a benzisoxazole-derivative, is an atypical antipsychotic agent.
Risperidone is a benzisoxazole-derivative antipsychotic agent. The drug has been described as an atypical antipsychotic agent. The principal active metabolite of risperidone is 9-hydroxyrisperidone (paliperidone); the clinical effects of risperidone result from the combined concentrations of risperidone and 9-hydroxyrisperidone.
The exact mechanism of antipsychotic action of risperidone has not been fully elucidated but may involve antagonism of both type 2 serotonergic (5-HT2) receptors and dopamine D2 receptors. Antagonism at other receptors (e.g., alpha1- and alpha2-adrenergic receptors, histamine H1 receptors) may contribute to other effects of risperidone.
Risperidone is a monoaminergic antagonist which exhibits high affinity for 5-HT2, dopamine D2, alpha1- and alpha2-adrenergic, and histamine H1 receptors. Risperidone exhibits low to moderate affinity for other serotonin receptor subtypes (e.g., 5HT1C, 5HT1A, 5HT1D), and weak affinity for dopamine D1 receptors and the haloperidol-sensitive sigma site. The drug possesses no affinity for cholinergic muscarinic or beta1- and beta2-adrenergic receptors.
Risperidone is well absorbed after oral administration, with peak drug plasma concentrations attained in approximately 1 hour. The absolute oral bioavailability of risperidone is 70%; the relative oral bioavailability from a tablet is 94% compared with a solution. Commercially available risperidone conventional and orally disintegrating tablets and oral solution are bioequivalent.
The mean peak plasma concentrations of the major active metabolite, 9-hydroxyrisperidone (paliperidone), occur at about 3 and 17 hours in patients who are extensive and poor metabolizers of cytochrome P-450 (CYP) 2D6, respectively. Steady state of risperidone is reached in 1 day in extensive metabolizers and expected in 5 days in poor metabolizers; 9-hydroxyrisperidone steady state is reached in 5-6 days in extensive metabolizers. Food does not affect the rate or extent of risperidone absorption.
After IM administration of risperidone (Risperdal(R) Consta(R)), there is a small initial release of the drug (<1% of dose) followed by a 3-week lag time; the main drug release starts from 3 weeks onward and is maintained for 4-6 weeks and then subsides by 7 weeks after the injection. Therefore, oral antipsychotic supplementation should be administered during the first 3 weeks of treatment with IM risperidone to maintain therapeutic levels until the main release of risperidone from the injection site has started. IM risperidone injections (Risperdal(R) Consta(R)) into the deltoid and gluteal areas are bioequivalent and therefore interchangeable.
With IM administration of extended-release risperidone injection every 2 weeks, steady-state plasma concentrations are achieved after 4 doses and are maintained 4-6 weeks after the last injection.
After a single IM risperidone injection (Rykindo(R)), the release profile consists of an initial release of the drug followed by a stable release phase of 2--4 weeks. The median time to peak concentration of risperidone and 9-hydroxyrisperidone combined are 14 and 17 days following administration of 25 mg and 50 mg of the drug, respectively. The combination of the release profile and the dosage regimen (IM injections every 2 weeks) of Rykindo(R) results in sustained concentrations within the dosing interval (every 2 weeks).
Steady-state plasma concentrations are reached after 2 injections and can be maintained for 2--3 weeks after the last injection.
Subcutaneous risperidone (Uzedy(R)) contains risperidone in a liquid delivery system. A depot forms following subcutaneous injection, providing sustained plasma levels of risperidone and 9-hydroxyrisperidone combined over 1 or 2 months. After subcutaneous administration, the median time to peak plasma concentrations for risperidone and 9-hydroxyrisperidone combined ranges from 8--14 days.
Therapeutic concentrations in plasma are achieved within 6--24 hours following the first injection. Steady-state levels of risperidone and 9-hydroxyrisperidone are approached within 2 months of Uzedy(R) initiation. Administration in the abdomen and upper arm results in similar pharmacokinetic profiles for all doses, therefore these injection sites can be used interchangeably.
Similar to Uzedy(R), subcutaneous risperidone (Perseris(R)) contains risperidone in a liquid delivery system. A depot forms following subcutaneous injection, providing sustained plasma levels of risperidone over the monthly dosing interval. After single subcutaneous injection, there are 2 absorption peaks for risperidone in plasma; the first peak is due to an initial release of the drug during the depot formation process, and the second peak (observed at 10 to 14 days after administration) is associated with the slow release of risperidone from the depot.
For both 9-hydroxyrisperidone and total active moiety, the median time to peak plasma concentrations of the first and second peak ranges from 4--48 hours and 7--11 days, respectively. Plasma concentrations of risperidone, 9-hydroxyrisperidone, and total active moiety approach steady-state levels after the first dose of Perseris(R).
Risperidone is rapidly distributed. The drug is approximately 90% protein bound (mainly to albumin and alpha1-acid glycoprotein); the major active metabolite (9-hydroxyrisperidone) is 77% protein bound. Risperidone is extensively metabolized, principally in the liver via CYP2D6, to the active metabolite (9-hydroxyrisperidone) which has similar pharmacologic activity to parent drug.
N-Dealkylation is a minor metabolic pathway. Risperidone is excreted principally in the urine (70%) and to much lesser extent, in the feces (14%).
After oral administration, overall mean elimination half-life for active moiety (risperidone plus 9-hydroxyrisperidone) is about 20 hours. After IM risperidone administration, the apparent half-life of the active moiety is 3-6 days. The elimination phase is complete approximately 7-8 and 6 weeks after the last injection of Risperdal(R) Consta(R) and Rykindo(R), respectively.
Following administration of Uzedy(R), the mean apparent half-life ranges between 14--22 days for risperidone, 9-hydroxyrisperidone, and risperidone and 9-hydroxyrisperidone combined. Following a single subcutaneous injection of Perseris(R), the mean apparent terminal half-life of risperidone ranges between 9--11 days; the mean apparent terminal half-life ranges between 8--9 days for both 9-hydroxyrisperidone and total active moiety.
Notably, CYP2D6 is subject to genetic polymorphism; extensive metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, while poor metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations, the pharmacokinetics of the active moiety (risperidone plus 9-hydroxyrisperidone) are similar after single and multiple doses in extensive and poor metabolizers. Following subcutaneous administration, plasma exposure to risperidone and 9-hydroxyrisperidone combined was similar in CYP2D6 extensive, intermediate, poor and non-poor metabolizers.
USES: This medication is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder, irritability associated with autistic disorder). Risperidone belongs to a class of drugs known as atypical antipsychotics. It works by helping to restore the balance of certain natural substances in the brain.
Generic name: risperidone
Pronunciation: (riss-PAIR-ih-doan)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Risperidone Odt
Indications
The following indications are listed for Risperidone Odt:
- Infantile Autism
- Mania Associated With Bipolar Disorder
- Mixed Bipolar I Disorder
- Schizophrenia
Also known as: Autism, Bipolar Mania, Childhood Autism, Dementia Praecox, Kanner's Syndrome, Mania Associated With Bipolar Affective Disorder, Manic Episode Associated With Bipolar Disorder, Manic Phase Bipolar Mood Disorder, Manic Phase Of Bipolar Mood Disorder, Manic Phase Of Manic-Depression, Parergasia.
Dosing
For patients who have never taken oral risperidone, tolerability should be established with oral risperidone prior to initiating treatment with IM or subcutaneous risperidone.
Risperidone is administered orally or by subcutaneous or IM injection. Risperidone is available as oral tablets, oral solution, and orally disintegrating tablets; extended-release IM injection (Risperdal(R) Consta(R); Rykindo(R)); and extended-release subcutaneous injection (Uzedy(R); Perseris(R)).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
In vitro studies indicate that risperidone is a relatively weak inhibitor of cytochrome P-450 (CYP) 2D6. Risperidone is metabolized by CYP2D6 to 9-hydroxyrisperidone (paliperidone), which has similar pharmacologic activity to risperidone; the clinical effects of risperidone result from the combined concentrations of risperidone and 9-hydroxyrisperidone.
In vitro, drugs metabolized by CYP1A1, CYP1A2, CYP2C9, CYP2C19, and CYP3A4 only weakly inhibit risperidone metabolism.
The interactions of IM or subcutaneous risperidone with coadministration of other drugs have not been studied. The following drug interaction data are based on studies with oral risperidone.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity to either risperidone or paliperidone (metabolite of risperidone) or to any of the excipients in the risperidone formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most frequent adverse effects of oral risperidone reported in >=5% of patients who received the drug in clinical trials and with an incidence of at least twice that of those receiving placebo were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain.
The most frequent adverse effects of IM risperidone in patients with schizophrenia (>=5%) were headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increase, pain in extremity, and dry mouth. The most frequent adverse effects of IM risperidone in patients with bipolar disorder were weight increase (5% in monotherapy trial) and tremor and parkinsonism (>=10% in adjunctive therapy trial).
The most frequent adverse effects of subcutaneous risperidone (Uzedy(R)) reported in >=5% of patients who received the drug in clinical trials and with an incidence greater than placebo were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. The most frequent injection site reactions with subcutaneous risperidone (Uzedy(R)) (>=5% and greater than placebo) were pruritus and nodule.
The most frequent adverse effects of subcutaneous risperidone (Perseris(R)) reported in >=5% of patients who received the drug in clinical trials and with an incidence of at least twice that of those receiving placebo were increased weight, sedation/somnolence, and musculoskeletal pain.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of risperidone for IM or subcutaneous administration have not been established in pediatric patients.
Safety and efficacy of oral risperidone for the treatment of schizophrenia in adolescents 13-17 years of age were demonstrated in 2 short-term clinical trials in 417 patients. Efficacy and safety of oral risperidone for the treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents 10-17 years of age were demonstrated in a 3-week, placebo-controlled study in 169 patients. The safety and efficacy of oral risperidone in children younger than 13 years of age with schizophrenia or younger than 10 years of age with bipolar I disorder have not been established.
Efficacy and safety of oral risperidone in the treatment of irritability associated with autistic disorder have been evaluated in 3 placebo-controlled trials in pediatric patients 5 to 17 years of age.
In clinical trials in 1885 children and adolescents treated with risperidone, 2 patients (0.1%) reportedly developed tardive dyskinesia, which resolved upon discontinuance of therapy.
Weight gain has been observed in children and adolescents during treatment with oral risperidone; clinical monitoring of weight is recommended during treatment.
Somnolence frequently occurred in placebo-controlled trials of oral risperidone in pediatric patients with autistic disorder. Most cases were mild to moderate in severity, occurred early during therapy (peak incidence during the first 2 weeks of therapy), and were transient (median duration of 16 days). Somnolence also was the most common adverse effect in clinical trials in children and adolescents with bipolar disorder as well as in schizophrenia clinical trials in adolescents; as in the autistic disorder trials, somnolence usually occurred early during therapy and was transient. Pediatric patients experiencing persistent somnolence may benefit from a change in dosage regimen.
Oral risperidone has been shown to elevate prolactin concentrations in children and adolescents as well as adults. In double-blind, placebo-controlled trials of up to 8 weeks' duration in children and adolescents 5-17 years of age, 49% of oral risperidone-treated patients had elevated prolactin concentrations compared with 2% of those receiving placebo. Similarly, in placebo-controlled trials in children and adolescents 10-17 years of age with bipolar disorder or adolescents 13-17 years of age with schizophrenia, 82-87% of risperidone-treated patients had elevated prolactin concentrations compared with 3-7% of placebo recipients. Increases in prolactin concentrations were dose dependent and generally greater in female than male patients across indications. In clinical trials conducted in 1885 children and adolescents, galactorrhea and gynecomastia reportedly occurred in 0.8 and 2.3%, respectively, of oral risperidone-treated patients.
The manufacturers state that the long-term effects of oral risperidone on growth and sexual maturation have not been fully evaluated in children and adolescents.
A pregnancy exposure registry is available that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including risperidone, during pregnancy. Clinicians are encouraged to enroll patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 or online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/.
Currently available data from published epidemiologic studies of pregnant women exposed to risperidone have not established a drug-associated risk of major birth defects, miscarriage, or adverse outcomes in the mother or fetus. However, there are risks to the mother (e.g., risk of relapse, hospitalization, suicide) associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including risperidone, during pregnancy. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth.
In animals, administration of oral risperidone to pregnant mice caused cleft palate at doses 3--4 times the maximum recommended human dose (MRHD), with maternal toxicity observed at 4 times the MRHD based on body surface area. Risperidone was not teratogenic in rats or rabbits at doses up to 6 times the MRHD based on body surface area. Oral risperidone administration to pregnant rats at 1.5 times the MRHD (based on body surface area) resulted in increased stillbirths and decreased birth weight. Impaired learning was observed in offspring of rats when the dams were dosed at 0.6 times the MRHD and offspring mortality increased at doses 0.1--3 times the MRHD based on body surface area. Subcutaneous administration of the risperidone delivery system to pregnant rats and rabbits during organogenesis caused developmental toxicity (e.g., post-implantation loss, decreased number of live fetuses, decreased fetal weight and fetal malformations), at doses that are 52 (rat) and 43 (rabbit) times the delivery system amount present in 120 mg risperidone subcutaneous injectable suspension based on body surface area.
Neonates exposed to antipsychotic agents, including risperidone, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive care unit support and prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately.
Risperidone and its principal active metabolite, 9-hydroxyrisperidone (paliperidone), are distributed into milk. Sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) have been reported in breast-fed infants exposed to risperidone. There are no data on the effects of risperidone on milk production.
Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for risperidone and any potential adverse effects on the breast-fed child from the drug or from the mother's underlying condition.
Monitor infants exposed to risperidone through breastmilk for excess sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements).
Oral risperidone: Like other alpha-adrenergic blocking agents, risperidone can induce orthostatic hypotension; the manufacturers state that the risk of this effect can be minimized by limiting the initial oral dosage of risperidone to 0.5 mg twice daily in geriatric patients followed by careful titration.
Risperdal(R) Consta(R): For otherwise healthy geriatric patients, the recommended IM risperidone dosage of the extended-release injection is 25 mg every 2 weeks. Oral risperidone (or another oral antipsychotic agent) should be given with the first risperidone extended-release injection and should be continued for 3 weeks to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site.
Rykindo(R): The manufacturer makes no specific dosage recommendations for this extended-release IM injection for geriatric patients.
Uzedy(R), Perseris(R): Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients, dosage selection for extended-release subcutaneous injections of risperidone should be cautious, usually initiated at lower dosages in such patients.
Clinical studies of oral risperidone for the management of schizophrenia did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Other clinical experience with oral risperidone has not identified differences in responses between geriatric and younger patients. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients, oral risperidone generally should be initiated at lower dosages in such patients. Although geriatric patients exhibit a greater tendency to orthostatic hypotension, the manufacturers state that its risk may be minimized by limiting the initial oral dosage to 0.5 mg twice daily, followed by careful titration and close monitoring of orthostatic vital signs in patients for whom this is of concern.
No differences in the tolerability of extended-release IM risperidone were observed in an open-label study in otherwise healthy geriatric patients and younger patients with schizophrenia or schizoaffective disorder. Therefore, the manufacturer states that extended-release IM risperidone dosage recommendations for otherwise healthy geriatric patients are the same as for younger adults.
Clinical studies of subcutaneous risperidone for the management of schizophrenia did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in geriatric patients, dosage selection for subcutaneous risperidone should be cautious, usually initiated at lower dosages in such patients.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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