Risperdal

Pronunciation

Generic Name: Risperidone
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

Warning(s)

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 .

Warning(s)

  • 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 Risperdal

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

Slideshow: 2013 Drug News Round-Up: Top 20 Stories

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

Risperdal 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 Risperdal

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 Risperdal

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

Risperdal 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

Actions

  • 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.

Risperidone

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 device, a Needle-Pro safety needle, and with 2 mL prefilled syringe diluent)

Janssen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Risperdal 0.25MG Tablets (JANSSEN): 30/$160.99 or 90/$463.96

Risperdal 0.5MG Tablets (JANSSEN): 30/$179.98 or 90/$507.98

Risperdal 1MG/ML Solution (JANSSEN): 60/$405.97 or 180/$1,182.91

Risperdal 1MG Tablets (JANSSEN): 30/$189.99 or 90/$527.98

Risperdal 2MG Tablets (JANSSEN): 30/$302.98 or 90/$881.01

Risperdal 3MG Tablets (JANSSEN): 30/$377.98 or 90/$1,049.01

Risperdal 4MG Tablets (JANSSEN): 30/$472.97 or 90/$1,384.97

Risperdal M-TAB 0.5MG Dispersible Tablets (JANSSEN): 28/$171.98 or 84/$492.97

Risperdal M-TAB 1MG Dispersible Tablets (JANSSEN): 28/$195.00 or 84/$569.95

RisperDAL M-TAB 4MG Dispersible Tablets (JANSSEN): 28/$542.99 or 56/$1,069.98

RisperiDONE 0.25MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$145.97 or 180/$399.93

RisperiDONE 0.5MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$179.99 or 180/$499.90

Risperidone 1MG/ML Solution (TEVA PHARMACEUTICALS USA): 30/$125.98 or 90/$359.97

RisperiDONE 1MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$195.99 or 180/$549.95

RisperiDONE 2MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$289.96 or 180/$829.89

RisperiDONE 3MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$300.01 or 180/$869.97

Risperidone 4MG Tablets (TEVA PHARMACEUTICALS USA): 60/$399.98 or 180/$1,159.97

RisperiDONE M-TAB 4MG Dispersible Tablets (PATRIOT PHARMACEUTICALS LLC): 28/$345.99 or 56/$675.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 13, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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a. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution and Risperdal M-TAB(risperidone) orally disintegrating tablets prescribing information. Titusville, NJ; 2006 Mar.

b. Janssen Pharmaceutica. Risperdal Consta (risperidone) long-acting injection prescribing information. Titusville, NJ; 2006 Mar.

c. GlaxoSmithKline Pharmaceuticals. Paxil (paroxetine hydrochloride) tablets and oral suspension prescribing information. 2005 Sep.

d. GlaxoSmithKline. Paxil CR (paroxetine hydrochloride) controlled-release tablets prescribing information. 2005 Sep.

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