Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: 3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8, 9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
Molecular Formula: C23H27FN4O2
CAS Number: 106266-06-2
Brands: Risperdal
Special Alerts:
[Posted 06/13/2011] ISSUE: FDA notified healthcare professionals and the public of medication error reports in which patients were given risperidone (Risperdal) instead of ropinirole (Requip) and vice versa. In some cases, patients who took the wrong medication needed to be hospitalized.
The FDA determined that the factors contributing to the confusion between the two products include:
Similarities of both the brand (proprietary) and generic (established) names
Similarities of the container labels and carton packaging
Illegible handwriting on prescriptions
Overlapping product characteristics, such as the drug strengths, dosage forms, and dosing intervals.
BACKGROUND: Risperidone (Risperdal) is an antipsychotic medication used to treat mental illnesses including schizophrenia, bipolar disorder, and irritability associated with autistic disorder. Ropinirole (Requip) is a dopamine agonist used in the treatment of Parkinson’s disease and Restless Legs Syndrome.
RECOMMENDATION: Healthcare Professionals are reminded to clearly print or spell out the medication name on prescriptions and make certain their patients know the name of their prescribed medication and their reason for taking it. For more information visit the FDA website at: and .
[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.
The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.
BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.
RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .
- Increased Mortality in Geriatric Patients
Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., risperidone, aripiprazole, olanzapine, quetiapine) compared with those receiving placebo (2.6%).98 a b
Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).98 a b
Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.98 a b (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)
Introduction
Atypical or second-generation antipsychotic agent.1 2 3 5 6 7 8 9 10 11 12 13 60
Uses for Risperidone
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Schizophrenia
Symptomatic management of schizophrenia.1 60 103 104
Bipolar Disorder
Short-term management (alone or in combination with lithium or divalproex sodium) of acute manic or mixed episodes associated with bipolar I disorder.1 99 100 101
Autistic Disorders
Management of severe behavioral problems associated with autistic disorders†; not shown to improve core symptoms of autism (e.g., language deficits, social withdrawal).31 32 33 34
Risperidone Dosage and Administration
Administration
Administer orally or IM.1 b
Establish tolerability with oral risperidone prior to initiating IM therapy.b
Oral Administration
Administer orally once or twice (in equally divided doses) daily without regard to meals.1 14
Just prior to administration of orally disintegrating tablet, remove blister from aluminum blister pack or child-resistant pouch; with dry hands, peel open blister package, place tablet on tongue to dissolve, and swallow with or without liquids.a Do not chew or divide orally disintegrating tablet.1
Oral solution may be administered with compatible beverages.1 (See Compatibility under Stability.)
When switching from other antipsychotic agents to risperidone, abrupt discontinuance of previous agent may be acceptable for some patients, but gradual discontinuance may be appropriate for others.1 In all cases, minimize period of overlapping antipsychotic administration.1
In patients being switched from long-acting (depot) parenteral antipsychotic therapy to oral risperidone therapy, administer first oral dose in place of next scheduled dose of the long-acting preparation.1
IM Administration
Administer by deep IM injection into upper outer quadrant of the gluteal area every 2 weeks, alternating buttocks.103 Do not administer IV.103
Administer only with needle and other components of dose pack supplied by manufacturer.103
Do not combine 2 different strengths of IM risperidone in a single administration.103
Reconstitution
Consult manufacturer’s labeling for instructions for using components of dose pack for reconstitution.103
Allow the risperidone dose pack to reach room temperature before reconstituting.103
Reconstitute vial containing risperidone extended-release microspheres only with diluent in prefilled syringe supplied by manufacturer.103 Inject entire contents of prefilled syringe and shake vial vigorously while holding plunger rod down with thumb for ≥10 seconds to ensure a homogeneous suspension (appears uniform, thick, milky).103
Upon suspension in diluent, immediate use is recommended because suspension will settle over time.103 If >2 minutes pass before administration, shake vigorously to resuspend.103 Must be used within 6 hours of reconstitution.103
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
If reinitiated after a drug-free period, titrate oral dosage as with initial therapy.1
Adults
Schizophrenia
Oral
Initially, 1 mg twice daily, with increases in increments of 1 mg twice daily on second and third day, as tolerated, to target dosage of 6–8 mg daily (once daily or in 2 equally divided doses) recommended by manufacturer.1 Make subsequent dosage adjustments at intervals of ≥7 days.1 2
Alternatively, an initial dosage of 1–2 mg daily, with increases in increments of 0.5–1 mg daily titrated over 6–7 days, as tolerated, to target dosage of 4 mg daily may be more appropriate in most otherwise healthy adult patients.30
Lower initial dosages (e.g., 1 mg daily) and slower dosage titrations to an initial target dosage of 2 mg daily may be appropriate for younger patients and those being treated for their first psychotic episode.30 Titrate dosage up to 4 mg daily depending on clinical response and adverse neurologic effects; 1–3 mg may be optimal.30
Maximal efficacy generally observed in dosage range of 4–8 mg daily; dosages >6 mg daily did not result in greater efficacy, but were associated with more adverse effects (e.g., extrapyramidal symptoms).1 15 30
Efficacy maintained for up to 2 years, but optimum duration of therapy currently is not known.1 23 In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; periodically reassess need for continued therapy.1 b
IM
25 mg IM every 2 weeks.103
Administer oral risperidone (or another antipsychotic agent) with the first IM risperidone injection and continue oral therapy for 3 weeks thereafter to ensure adequate therapeutic plasma concentrations are maintained prior to main release of risperidone from injection site.103 (See Bioavailability and Plasma Concentrations under Pharmacokinetics.)
Some patients not responding to 25 mg may benefit from dosages of 37.5 or 50 mg IM every 2 weeks, although dose response for efficacy not established.103
Increase dosage at intervals of 4 weeks.103
If reinitiating IM risperidone after a drug-free period, administration of oral risperidone (or another antipsychotic agent) for supplementation will be needed.103
Bipolar Disorder
Acute Manic or Mixed Episodes
Oral
Initially 2–3 mg once daily.104 99 100 101
Adjust dosage, if indicated, in increments or decrements of 1 mg daily at intervals of not less than 24 hours.104 99
Antimanic efficacy demonstrated in dosage range of 1–6 mg daily; dosages >6 mg daily not studied.104 99
Not studied >3 weeks.104 If elect to use risperidone for extended periods, periodically reevaluate long-term risks and benefits for the individual patient.104
Prescribing Limits
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Adults
Schizophrenia
Oral
Dosages >6 mg (in 2 divided doses) generally not recommended; safety of dosages >16 mg daily not established.1
IM
Maximum 50 mg every 2 weeks.103
Bipolar Disorder
Acute Manic or Mixed Episodes
Oral
Safety and efficacy of dosages >6 mg not established.1
Special Populations
Hepatic Impairment
Oral: Initially, 0.5 mg twice daily in patients with severe hepatic impairment; increase dosage in increments of ≤0.5 mg twice daily.1 If increase in dosage beyond 1.5 mg twice daily is planned, adjust at intervals of at least 1 week; slower titration may be appropriate in some patients.1
IM: Titrate oral therapy prior to initiation of IM therapy in patients with hepatic impairment; if an oral dosage of ≥2 mg daily is well tolerated, administer 25 mg IM every 2 weeks.103 Administer oral risperidone with the first IM risperidone injection and continue oral supplementation for 3 weeks thereafter.103
Renal Impairment
Oral: Initially, 0.5 mg twice daily in patients with severe renal impairment; increase dosage in increments of ≤0.5 mg twice daily.1 If increase in dosage beyond 1.5 mg twice daily is planned, adjust at intervals of at least 1 week; slower titration may be appropriate in some patients.1
IM: Titrate oral therapy prior to initiation of IM therapy in patients with renal impairment; if an oral dosage of ≥2 mg daily is well tolerated, administer 25 mg IM every 2 weeks.103 Administer oral risperidone with first IM risperidone injection and continue oral supplementation for 3 weeks thereafter.103
Geriatric, Debilitated, or Hypotensive Patients
Oral: Initially, 0.5 mg twice daily in geriatric or debilitated patients and patients either predisposed to hypotension or for whom hypotension would pose a risk; increase dosage in increments of ≤0.5 mg twice daily.1 If increase in dosage beyond 1.5 mg twice daily is planned, adjust at intervals of at least 1 week; slower titration may be appropriate in some patients.1 If a once-daily dosage regimen is considered, titrate on a twice-daily regimen for 2–3 days at the target dosage before switching to a once-daily regimen.103
Alternatively, in geriatric patients, initially give 0.25 mg daily; gradually increase dosage as tolerated.30
IM: 25 mg every 2 weeks in otherwise healthy geriatric patients.103 Administer oral risperidone with the first IM risperidone injection and continue oral supplementation for 3 weeks thereafter.103
Cautions for Risperidone
Contraindications
Known hypersensitivity to risperidone or any ingredient in the formulation.1 103
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Increased Mortality in Geriatric Patients with Dementia-related Psychosis
Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.98 103 a
Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.98 103 a (See Boxed Warning and see Geriatric Use under Cautions.)
Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported in patients receiving antipsychotic agents.1
Tardive Dyskinesia
Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, has been reported.1 21 Consider discontinuance of risperidone.1
Cerebrovascular Effects
Adverse cerebrovascular effects (e.g., stroke, TIA), sometimes fatal, reported in geriatric patients (73–97 years of age) with dementia-related psychosis receiving risperidone.1 (See Geriatric Use under Cautions.)
Hyperglycemia and Diabetes Mellitus
Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents, including risperidone.1 44 45 46 47 48 49 50 51 52 53 54 55 56 57 71 72 73 74 78 97 Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).1 45 46 47 48 49 50 51 52 53 54 55 56 If manifestations of hyperglycemia occur, test for diabetes mellitus.1 45 46 47 48 49 50 51 52 53 54 55 56
General Precautions
Orthostatic Hypotension
Orthostatic hypotension reported.1 Use with caution in patients with known cardiovascular or cerebrovascular conditions that would predispose them to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy), in geriatric patients, and in patients with renal or hepatic impairment.1 103
Nervous System Effects
Possible risk of seizures.1
Disruption of ability to regulate core body temperature possible; both hypothermia and hyperthermia reported.103 104 Use caution in patients exposed to temperature extremes.103 104
Somnolence reported.1 Potential impairment of judgment, thinking, or motor skills.1
Antiemetic effect demonstrated in animals; also may occur in humans and mask manifestations of overdosage with certain drugs or of underlying conditions (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).1
GI Effects
Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., those with advanced Alzheimer’s dementia).
Hematologic Effects
Thrombotic thrombocytopenic purpura reported in at least one patient; relationship to risperidone not established.1
Suicide
Attendant risk with psychotic illnesses; closely supervise high-risk patients.1 Prescribe oral risperidone in the smallest quantity consistent with good patient management to reduce the risk of overdosage.1
Sexual Dysfunction
Priapism reported rarely with oral risperidone.1
Endocrine Effects
Elevated prolactin concentrations possible, which persist during chronic administration.1
Metabolic Effects
Weight gain possible.1
Phenylketonuria
Each 0.5, 1, 2, 3, or 4 mg Risperdal M-TAB orally disintegrating tablet contains aspartame (e.g., Nutrasweet), which is metabolized in the GI tract to provide 0.14, 0.28, 0.42, 0.63, or 0.84 mg of phenylalanine per tablet, respectively.39 40 41 42 43 a
Osteodystrophy and Tumors in Animals
Osteodystrophy, renal tubular tumors, and adrenomedullary pheocytochromocytomas demonstrated in rats following IM administration of extended-release risperidone; not observed previously with oral risperidone.103 Relevance to humans currently not known.103
Concomitant Illnesses
Experience in patients with certain concomitant diseases is limited.a b
Possible increased risk of NMS and increased sensitivity to antipsychotic agents in patients with parkinsonian syndrome or dementia with Lewy bodies; manifestations of sensitivity may include confusion, obtundation, postural instability with more frequent falling, or extrapyramidal adverse effects104 a b
Patients with recent history of MI or unstable heart disease generally were excluded from premarketing clinical studies.a b Use with caution in patients with altered metabolism or hemodynamics.a b
Specific Populations
Pregnancy
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Category C.1 103
Lactation
Risperidone and an active metabolite (9-hydroxyrisperidone) are distributed into milk.1 103 Women receiving oral risperidone should not breast-feed.1 Women treated with extended-release IM risperidone should not breast-feed during or for at least 12 weeks after the last injection.103
Pediatric Use
Safety and efficacy not established in children <18 years of age.1 103 However, has been used in a limited number of children 5–7 years of age for treatment of autistic disorders.31 33 (See Autistic Disorders under Uses.)
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 Use with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly. (See Boxed Warning and see Cerebrovascular Effects under Cautions.)1
Minimize risk of orthostatic hypotension with lower initial dosage and careful dosage titration; monitor orthostatic vital signs in patients for whom hypotension is a concern.1 (See Special Populations under Dosage and Administration and see Orthostatic Hypotension under Cautions.)
No differences in tolerance of extended-release IM risperidone were observed in one study in patients ≥65 years of age with schizophrenia or schizoaffective disorder; no dosage adjustment recommended for otherwise healthy geriatric patients.103
Increased mortality reported in geriatric patients receiving risperidone concomitantly with furosemide (but not other diuretics) for the management of dementia-related psychosis.a b
Possible increased risk of death in geriatric patients with dementia-related psychosis regardless of concomitant use with furosemide.98 a b Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., risperidone, aripiprazole, olanzapine, quetiapine) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).98 a b In addition, adverse cerebrovascular effects, sometimes fatal, reported in geriatric patients with dementia-related psychosis receiving risperidone.1 (See Cerebrovascular Effects under Cautions.)
Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.98 a b (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)
Hepatic Impairment
Possible increases in risperidone free fraction, resulting in enhanced effect; dosage adjustment recommended.1 (See Special Populations under Dosage and Administration.)
Renal Impairment
Possible decreased elimination compared with normal adults; dosage adjustment recommended.1 (See Special Populations under Dosage and Administration.)
Common Adverse Effects
Anxiety, somnolence, extrapyramidal symptoms, dizziness, constipation, nausea, dyspepsia, rhinitis, rash, tachycardia, dystonia, akathisia, abnormal vision, increased saliva, fatigue, weight increase.1 a b
Interactions for Risperidone
Metabolized by CYP2D6 to 9-hydroxyrisperidone, which has similar pharmacologic activity.a b May weakly inhibit CYP2D6.1
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors or inducers of CYP2D6; potential pharmacokinetic interaction (altered risperidone metabolism and plasma concentrations of the active moiety [risperidone plus 9-hydroxyrisperidone]).1 (See Metabolism under Pharmacokinetics.) In vitro, drugs metabolized by CYP1A1, CYP1A2, CYP2C9, CYP2C19, and CYP3A4 only weakly inhibit risperidone metabolism.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Drugs metabolized by CYP2D6; substantial pharmacokinetic interaction unlikely.1
Specific Drugs1
Drug | Interaction | Comments |
|---|---|---|
Alcohol | Possible additive CNS effects1 | Advise patients to avoid alcohol1 |
Amitriptyline | No effects on pharmacokinetics of risperidone or active antipsychotic moietya b | |
Carbamazepine | Decreased plasma risperidone and 9-hydroxyrisperidone concentrations1 | Titrate risperidone dosage accordingly, particularly during carbamazepine initiation or discontinuance1 Patients receiving IM risperidone may need dosage increase or supplemental oral risperidone when carbamazepine is initiated; consider reducing IM risperidone dosage 2–4 weeks before discontinuance of carbamazepine103 |
Cimetidine | Increased risperidone bioavailability, but no effect on AUC of active antipsychotic moietya b | |
Clozapine | Possible decreased risperidone clearance1 | |
CNS agents | Additive CNS effects1 | |
Digoxin | No clinically relevant effect on digoxin pharmacokinetics1 | |
Donepezil | No substantial effects on donepezil pharmacokinetics1 | |
Dopamine agonists | Possible antagonistic effects1 | |
Erythromycin | No substantial interactions1 | |
Fluoxetine | Increased plasma risperidone concentrations; no effect on 9-hydroxyrisperidone concentrations1 103 | Reevaluate risperidone dosage during fluoxetine initiation or discontinuance;1 consider reducing dosage of IM risperidone 2–4 weeks before initiating fluoxetine103 |
Galantamine | No substantial effects on galantamine pharmacokinetics1 | |
Hypotensive agents | Additive hypotensive effects1 | Use with caution1 |
Levodopa | Possible antagonistic effects1 | |
Lithium | No effect on lithium AUC or peak plasma concentrations1 | |
Paroxetine | Increased plasma risperidone concentrations, decreased plasma 9-hydroxyrisperidone (active metabolite) concentrations, and increased plasma concentrations of active antipsychotic moiety1 c d Generally well tolerated; possible risk of parkinsonian symptomsd | Monitor patients carefully and consider possible monitoring of plasma risperidone concentrations;d reevaluate risperidone dosage during paroxetine initiation or discontinuance1 Consider lower initial dosage of paroxetine (10–20 mg daily)d |
Phenobarbital | Possible decreased plasma risperidone and 9-hydroxyrisperidone concentrations1 | Decreased risperidone efficacy possible1 Patients receiving IM risperidone may need dosage increase or supplemental oral risperidone when phenobarbital is initiated; consider reducing IM risperidone dosage 2–4 weeks before discontinuance of phenobarbital103 |
Phenytoin | Possible decreased plasma risperidone and 9-hydroxyrisperidone concentrations1 | Decreased risperidone efficacy possible1 Patients receiving IM risperidone may need dosage increase or supplemental oral risperidone when phenytoin is initiated; consider reducing IM risperidone dosage 2–4 weeks before discontinuance of phenytoin103 |
Ranitidine | Increased risperidone bioavailability and AUC of active antipsychotic fractiona b | |
Rifampin | Possible decreased plasma risperidone and 9-hydroxyrisperidone concentrations1 | Decreased risperidone efficacy possible1 Patients receiving IM risperidone may need dosage increase or supplemental oral risperidone when rifampin is initiated; consider reducing IM risperidone dosage 2–4 weeks before discontinuance of rifampin103 |
Valproate | Possible increase in peak plasma valproate concentration1 |
Risperidone Pharmacokinetics
Absorption
Bioavailability
Well absorbed after oral administration, with peak plasma concentrations attained in approximately 1 hour.1
Absolute bioavailability is 70%; relative oral bioavailability from a tablet is 94% compared with a solution.1
Commercially available conventional and orally disintegrating tablets and oral solution are bioequivalent.1
After IM administration, there is a small initial release of the drug (<1% of dose) followed by a 3-week lag time; main drug release starts from 3 weeks onward and is maintained for 4–6 weeks.103
Food
Food does not affect rate or extent of absorption.1
Plasma Concentrations
With IM administration of extended-release injection risperidone every 2 weeks, steady-state plasma concentrations achieved after 4 doses and are maintained 4–6 weeks after the last injection.103
Distribution
Extent
Rapidly distributed.1 Crosses the placenta in rats; not known if crosses the placenta in humans.1 Risperidone and its active metabolite distribute into milk.1
Plasma Protein Binding
90% (mainly albumin and α1-acid glycoprotein); major active metabolite (9-hydroxyrisperidone) is 77% protein bound.1
Elimination
Metabolism
Extensively metabolized, principally in the liver via CYP2D6, to an active metabolite (9-hydroxyrisperidone); N-dealkylation is minor metabolic pathway.1
9-Hydroxyrisperidone has similar pharmacologic activity to parent drug; clinical effects result from combined concentrations of risperidone and 9-hydroxyrisperidone.a b
Elimination Route
Excreted principally in urine (70%) and to much lesser extent, in feces (14%).1
Half-life
After oral administration, overall mean elimination half-life for active moiety (risperidone plus 9-hydroxyrisperidone) is about 20 hours.1
After IM administration, apparent half-life of active moiety is 3–6 days.103 Elimination phase is complete approximately 7–8 weeks after last injection.103
Special Populations
In patients with moderate to severe renal impairment, total active moiety clearance (i.e., sum of risperidone and its active metabolite) is decreased by 60% compared with that of young healthy adults.1 Dosage adjustment recommended.1 (See Special Populations under Dosage and Administration.)
In patients with hepatic impairment, pharmacokinetics were similar to those in young healthy adults; however, the mean free-fraction of risperidone in plasma was increased by about 35% due to diminished albumin and α1-acid glycoprotein concentrations.1 Dosage adjustment recommended.1 (See Special Populations under Dosage and Administration.)
In geriatric patients receiving oral risperidone, renal clearance was decreased and half-lives were prolonged for both risperidone and its active metabolite compared with younger adults.1 Adjust dosage accordingly.1 However, in otherwise healthy patients ≥65 years of age treated with IM risperidone for up to 12 months, pharmacokinetics were similar to younger adults; no dosage adjustment recommended in such patients.103
CYP2D6 is subject to genetic polymorphism; extensive metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, while poor metabolizers convert it much more slowly.1 Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations, the pharmacokinetics of the active moiety are similar after single and multiple doses in extensive and poor metabolizers.1
Stability
Storage
Oral
Tablets
15–25°C.1 Protect from light and moisture.1
Orally Disintegrating Tablets
15–25°C.1 Do not remove from manufacturer’s pack.a
Solution
15–25°C.1 Protect from light and freezing.1
Parenteral
Extended-release Injection
Store entire dose pack at 2–8°C; protect from light.103 If refrigeration unavailable, store at temperatures not >25°C for ≤7 days prior to administration.103
After mixing with diluent, use within 6 hours of suspension; do not expose to temperatures >25°C.103
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Oral
Solution
May be mixed with water, coffee, orange juice, or low-fat milk.1 Not compatible with cola or tea.1
ActionsActions
Exact mechanism of antipsychotic action has not been fully elucidated; may involve antagonism of central type 2 serotonergic (5-HT2) receptors and central dopamine D2 receptors.1 2 3 8 10 12 13 15
Antagonism at other receptors (e.g., α1- and α2-adrenergic receptors, histamine H1 receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).1
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Risk of somnolence.1 Importance of avoiding driving, operating machinery, or performing hazardous tasks until gain experience with drug’s effects.1
Risk of orthostatic hypotension.1 103 Importance of using nonpharmacologic methods (e.g., sitting on edge of bed for several minutes upon waking, slowly rising from sitting to standing position) to minimize effects.103
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).a b
Importance of avoiding alcohol during risperidone therapy.1
Importance of avoiding overheating or dehydration.a b
Importance of informing patients with phenylketonuria that risperidone orally disintegrating tablets contain aspartame.39 40 41 42 43 a
Importance of women informing clinicians if they are or plan to become pregnant during oral risperidone therapy or for 12 weeks after last risperidone IM injection.1 103
Breast-feeding not recommended.1 103 Importance of women informing clinicians if they are or plan to breast-feed during oral risperidone therapy or for 12 weeks after last IM risperidone IM injection.1 103
Importance of informing patients of other important precautionary information.1 103 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution | 1 mg/mL | Risperdal | Janssen |
Tablets | 0.25 mg | Risperdal (with propylene glycol; scored) | Janssen | |
0.5 mg | Risperdal (with propylene glycol; scored) | Janssen | ||
1 mg | Risperdal (with propylene glycol; scored) | Janssen | ||
2 mg | Risperdal (with propylene glycol; scored) | Janssen | ||
3 mg | Risperdal (with propylene glycol; scored) | Janssen | ||
4 mg | Risperdal (with propylene glycol; scored) | Janssen | ||
Tablets, orally disintegrating | 0.5 mg | Risperdal M-TAB (with aspartame) | Janssen | |
1 mg | Risperdal M-TAB (with aspartame) | Janssen | ||
2 mg | Risperdal M-TAB (with aspartame) | Janssen | ||
3 mg | Risperdal M-TAB (with aspartame) | Janssen | ||
4 mg | Risperdal M-TAB (with aspartame) | Janssen | ||
Parenteral | For injectable suspension, extended-release, for IM use | 25 mg | Risperdal Consta (available as dose pack containing a SmartSite needle-free vial access device, a Needle-Pro safety needle, and with 2 mL prefilled syringe diluent) | Janssen |
37.5 mg | Risperdal Consta (available as dose pack containing a SmartSite needle-free vial access device, a Needle-Pro safety needle, and with 2 mL prefilled syringe diluent) | Janssen | ||
50 mg | Risperdal Consta (available as dose pack containing a SmartSite needle-free vial access de |
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