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Risperdal Consta risperidone Kit — NDC 50458-0306-11 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Risperdal Consta risperidone Kit — NDC 50458-306-11 (Billing 50458-0306-11)

by Janssen Pharmaceuticals, Inc. · 1 KIT in 1 BOX * 2 mL in 1 VIAL * 2 mL in 1 SYRINGE

This is a package of Risperdal Consta risperidone Kit from Janssen Pharmaceuticals, Inc., marketed since Oct 2003 and currently FDA-listed; retail pharmacies pay about $636.88 per unit (NADAC). It is this product's only package size.

NDC 50458-0306-11
🏷️ FDA NDC (as labeled) 50458-306-11 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 50458-306-11 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
50458 labeler · 306 product · 11 package
Package marketed since
Oct 29, 2003
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 5045830611 8
Medicaid fills, this package
8,727 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50458-306-11
Product NDC 50458-306
11-digit billing NDC 50458030611
NCPDP billing unit EA — each (per item)
RxCUI 402010, 402011, 402012, 706822, 706825, 706827, 706829, 706831
Application # NDA021346
SPL Set ID bb34ee82-d2c2-43b8-ba21-2825c0954691
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2003-10-29
Dosage form KIT
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 5907007010G220
GPI class RisperDAL Consta
GCN Seq No 052934
GCN 20217
HICL code 025509
Ingredient (HICL) Risperidone Microspheres
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H7
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)
HIC3 code H7T
Therapeutic class — specific (HIC3) Antipsychotic,Atypical,Dopamine,Serotonin Antagnst
AHFS code 28:16.08.04
AHFS class Atypical Antipsychotics
FDB label name RISPERDAL CONSTA 25 MG VIAL
FDB brand name Risperdal Consta
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 052934
  • GCN: 20217
  • GPI-14 (Medi-Span): 5907007010G220
  • HICL (First Databank): 025509
  • AHFS class code: 28:16.08.04
  • RxCUI (RxNorm): 402010
Why two NDCs? The FDA registers this code as 50458-306-11 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 50458-0306-11. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Atypical Antipsychotic class.

Pharmacologic class Atypical Antipsychotic
Drug family (ATC) Other antipsychotics
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name RISPERDAL CONSTA 25 MG VIAL Ingredient Risperidone Microspheres
📗 Our plain-language guide HelloPharmacist
  • It treats schizophrenia and bipolar I disorder. The oral forms also treat irritability linked to autistic disorder in children and adolescents. Which condition applies depends on t...
  • Oral risperidone can be taken with or without food, because food doesn't change how well it's absorbed. Take it as your prescriber directed. The injections are given by a healthcar...
  • Common ones include sleepiness, dizziness, restlessness, tremor, stiffness, nausea, constipation, dry mouth and weight gain. Tell your prescriber if they bother you. Don't stop on...
  • Call for fever with muscle stiffness or confusion, uncontrolled movements, stroke symptoms, seizures, signs of high blood sugar like extreme thirst, or a painful erection that won'...
📖 Read our full Risperidone guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $636.878 —
Medicaid paysCMS SDUD · 12 mo $612.24 —
Medicare drug plans payPart D · Q2 2026 $629.72 —
Medicare Part B allowsASP · J2794 $11.105 / J2794 unit —
NADAC price history (per ea) — tap or hover for the price & month
Apr 2021 Dec 2025 Jun 2026 Sep 2026 $639.803 $510.776
▲ Up 25% over the last 10 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)50458-306-11
11-digit billing NDC50458-0306-11
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ2794
DescriptorINJECTION, RISPERIDONE (RISPERDAL CONSTA), 0.5 MG
Billing units / pkg50 units
How the units are derivedThis package is 1 EA; the HCPCS unit is 0.5 MG, so one package = 50 billing units.
Medicare Part B spend (2026 (Q1))$388,388 · 517 claims · $751.23 per claim (all NDCs under J2794)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
50458-0306-11 You're viewing this Main listing 1 KIT in 1 BOX * 2 mL in 1 VIAL * 2 mL in 1 SYRINGE 2003-10-29 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Risperdal Consta 50458-0309-11 Janssen 1 kit $317.931 AB Availability likely save 50%
Risperidone 00480-1232-08 Teva 1 kit $355.232 AB Availability likely save 44%
Risperidone 70121-2626-05 Amneal 1 kit $355.232 AB Availability likely save 44%
risperidone 70748-0270-13 Lupin 1 kit $355.232 AB Availability likely save 44%
Risperidone 00480-1342-08 Teva 1 kit $566.404 AB Availability likely save 11%
risperidone 70748-0271-13 Lupin 1 kit $566.404 AB Availability likely save 11%
Risperdal Constathis 50458-0306-11 Janssen 1 kit $636.878 AB Availability likely —
Risperidone 00480-1453-08 Teva 1 kit $760.218 AB Availability likely +19%
risperidone 70748-0272-13 Lupin 1 kit $760.218 AB Availability likely +19%
Risperdal Consta 50458-0307-11 Janssen 1 kit $949.938 AB Availability likely +49%
Risperdal Consta 50458-0308-11 Janssen 1 kit $1,273.390 AB Availability likely +100%
Rykindo extended-release microspheres 72526-0102-11 Shandong 1 kit — — FDA listed —
Rykindo extended-release microspheres 72526-0103-11 Shandong 1 kit — — Discontinued —
Risperidone 71161-0131-01 Synergy 1 kit — — FDA listed —
Risperidone 00480-1554-08 Teva 1 kit — AB FDA listed —
Risperidone 71161-0132-01 Synergy 1 kit — — FDA listed —
Rykindo extended-release microspheres 72526-0104-11 Shandong 1 kit — — Discontinued —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2003
On the market since
Oct 2003
📍
2026
Currently FDA-listed
23 years listed
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Risperidone inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive ingredients.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerJanssen Pharmaceuticals, Inc.
Application holderJANSSEN PHARMACEUTICALS INC
FDA applicationNDA021346 (NDA)
Labeler code50458
First marketedOct 2003
Product typeHuman Prescription Drug
Portfolio57 products on file

More NDCs from Janssen Pharmaceuticals, Inc. labeler code 50458

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📖 Instructions for Use 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 92 words ▾

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. RISPERDAL CONSTA is not approved for the treatment of patients with dementia-related psychosis. [see Warnings and Precautions (5.1) ] WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

RISPERDAL CONSTA is not approved for use in patients with dementia-related psychosis. ( 5.1 )

🎯 Indications and Usage 90 words ▾

1 INDICATIONS AND USAGE RISPERDAL CONSTA is an atypical antipsychotic indicated: for the treatment of schizophrenia. ( 1.1 ) as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder. ( 1.2 )

1.1Schizophrenia RISPERDAL CONSTA (risperidone) is indicated for the treatment of schizophrenia [see Clinical Studies (14.1) ].

1.2Bipolar Disorder RISPERDAL CONSTA is indicated as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder [see Clinical Studies (14.2 , 14.3) ] .

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For patients who have never taken oral RISPERDAL, it is recommended to establish tolerability with oral RISPERDAL prior to initiating treatment with RISPERDAL CONSTA. RISPERDAL CONSTA should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. Each injection should be administered by a health care professional using the appropriate enclosed safety needle [see Dosage and Administration (2.8) ] .

For deltoid administration, use the 1-inch needle alternating injections between the two arms. For gluteal administration, use the 2-inch needle alternating injections between the two buttocks. Do not administer intravenously.

For patients who have never taken oral RISPERDAL, tolerability should be established with oral RISPERDAL prior to initiating treatment with RISPERDAL CONSTA. ( 2 ) Administer by deep intramuscular (IM) deltoid or gluteal injection. Each injection should be administered by a health care professional using the appropriate enclosed safety needle (1-inch for deltoid administration alternating injections between the two arms and 2-inch for gluteal administration alternating injections between the two buttocks).

Do not administer intravenously. ( 2 ) 25 mg intramuscular (IM) every 2 weeks. Patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg.

The maximum dose should not exceed 50 mg every 2 weeks. ( 2 ) Oral RISPERDAL (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA, and continued for 3 weeks (and then discontinued) to ensure adequate therapeutic plasma concentrations from RISPERDAL CONSTA. ( 2 ) Upward dose adjustment of RISPERDAL CONSTA should not be made more frequently than every 4 weeks.

Clinical effects of each upward dose adjustment should not be anticipated earlier than 3 weeks after injection. ( 2 ) Avoid inadvertent administration into a blood vessel. ( 5.16 ) See Full Prescribing Information Section 2.8 for instructions for use.

2.1Schizophrenia The recommended dose for the treatment of schizophrenia is 25 mg IM every 2 weeks. Although dose response for effectiveness has not been established for RISPERDAL CONSTA, some patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg. The maximum dose should not exceed 50 mg RISPERDAL CONSTA every 2 weeks.

No additional benefit was observed with dosages greater than 50 mg RISPERDAL CONSTA; however, a higher incidence of adverse effects was observed. The efficacy of RISPERDAL CONSTA in the treatment of schizophrenia has not been evaluated in controlled clinical trials for longer than 12 weeks. Although controlled studies have not been conducted to answer the question of how long patients with schizophrenia should be treated with RISPERDAL CONSTA, oral risperidone has been shown to be effective in delaying time to relapse in longer-term use.

It is recommended that responding patients be continued on treatment with RISPERDAL CONSTA at the lowest dose needed. The physician who elects to use RISPERDAL CONSTA for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.2Bipolar Disorder The recommended dose for monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder is 25 mg IM every 2 weeks. Some patients may benefit from a higher dose of 37.5 mg or 50 mg. Dosages above 50 mg have not been studied in this population.

The physician who elects to use RISPERDAL CONSTA for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3General Dosing Information A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentrations [see Drug Interactions (7.11) ] or in pati… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 103 words ▾

3 DOSAGE FORMS AND STRENGTHS RISPERDAL CONSTA is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, and 50 mg risperidone. It is provided as a single-use dose pack, consisting of a vial containing the risperidone microspheres, a pre-filled syringe containing 2 mL of diluent for RISPERDAL CONSTA, a vial adapter, and two Terumo SurGuard 3 Needles for intramuscular injection (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration).

Vial kits: 12.5 mg, 25 mg, 37.5 mg, and 50 mg ( 3 )

⛔ Contraindications 70 words ▾

4 CONTRAINDICATIONS RISPERDAL CONSTA is contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the RISPERDAL CONSTA formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. Paliperidone is a metabolite of risperidone.

Known hypersensitivity to risperidone, paliperidone, or to any excipients in RISPERDAL CONSTA. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis. RISPERDAL CONSTA is not approved for use in patients with dementia-related psychosis ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring ( 5.3 ) Tardive Dyskinesia: Discontinue treatment if clinically appropriate ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk.

These metabolic changes include hyperglycemia, dyslipidemia, and weight gain. ( 5.5 ) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes.

( 5.5 ) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.5 ) Weight Gain: Significant weight gain has been reported. Monitor weight gain.

( 5.5 ) Hyperprolactinemia: Risperidone treatment may elevate prolactin levels. Long-standing hyperprolactinemia, when associated with hypogonadism, can lead to decreased bone density in men and women. ( 5.6 ) Orthostatic hypotension: associated with dizziness, tachycardia, bradycardia, and syncope can occur, especially during initial dose titration with oral risperidone.

Use caution in patients with cardiovascular disease, cerebrovascular disease, and conditions that could affect hemodynamic responses. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics, including RISPERDAL CONSTA. Patients with history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood cell count (CBC) monitored frequently during the first few months of therapy and discontinuation of RISPERDAL CONSTA should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.

( 5.9 ) Potential for cognitive and motor impairment: has potential to impair judgment, thinking, and motor skills. Use caution when operating machinery, including automobiles. ( 5.10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold.

( 5.11 ) Dysphagia: Esophageal dysmotility and aspiration can occur. Use cautiously in patients at risk for aspiration pneumonia. ( 5.12 ) Priapism: has been reported.

Severe priapism may require surgical intervention. ( 5.13 ) Avoid inadvertent administration into a blood vessel. ( 5.15 )

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

RISPERDAL CONSTA (risperidone) is not approved for the treatment of dementia-related psychosis [see Boxed Warning ] .

5.2Cerebrovascular Adverse Events, Including Stroke, in Elderly Patien… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Increased mortality in elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3) ] Tardive dyskinesia [see Warnings and Precautions (5.4) ] Metabolic changes [see Warnings and Precautions (5.5) ] Hyperprolactinemia [see Warnings and Precautions (5.6) ] Orthostatic hypotension [see Warnings and Precautions (5.7) ] Falls [see Warnings and Precautions (5.8) ] Leukopenia/Neutropenia and Agranulocytosis [see Warnings and Precautions (5.9) ] Potential for cognitive and motor impairment [see Warnings and Precautions (5.10) ] Seizures [see Warnings and Precautions (5.11) ] Dysphagia [see Warnings and Precautions (5.12) ] Priapism [see Warnings and Precautions (5.13) ] Disruption of body temperature regulation [see Warnings and Precautions (5.14) ] Avoidance of inadvertent injection into a blood vessel [see Warnings and Precautions (5.15) ] Osteodystrophy and tumors in animals [see Warnings and Precautions (5.16) ] The most common adverse reactions in clinical trials in patients with schizophrenia (≥ 5%) were: headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increased, pain in extremity, and dry mouth.

The most common adverse reactions in the double-blind, placebo-controlled periods of the bipolar disorder trials were weight increased (5% in the monotherapy trial) and tremor and parkinsonism (≥ 10% in the adjunctive treatment trial). The most common adverse reactions that were associated with discontinuation from the 12-week double-blind, placebo-controlled trial in patients with schizophrenia (causing discontinuation in ≥1% of patients) were agitation, depression, anxiety, and akathisia. Adverse reactions that were associated with discontinuation from the double-blind, placebo-controlled periods of the bipolar disorder trials were hyperglycemia (one patient in the monotherapy trial) and hypokinesia and tardive dyskinesia (one patient each in the adjunctive treatment trial).

The data described in this section are derived from a clinical trial database consisting of 2392 patients exposed to one or more doses of RISPERDAL CONSTA for the treatment of schizophrenia. Of these 2392 patients, 332 were patients who received RISPERDAL CONSTA while participating in a 12-week double-blind, placebo-controlled trial. Two hundred two (202) of the 332 were schizophrenia patients who received 25 mg or 50 mg RISPERDAL CONSTA.

The conditions and duration of treatment with RISPERDAL CONSTA in the other clinical trials varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer-term (up to 4 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs. In addition to the studies in patients with schizophrenia, safety data are presented from a trial assessing the efficacy and safety of RISPERDAL CONSTA when administered as monotherapy for maintenance treatment in patients with bipolar I disorder.

The subjects in this multi-center, double-blind, placebo-controlled study were adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who were stable on risperidone (oral or long-acting injection), were stable on other antipsychotics or mood stabilizers, or were experiencing an acute episode. After a 3-week period of treatment with open-label oral risperidone (N=440), subjects who demonstrated an initial response to oral risperidone in this period and those who were stable on rispe… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS The interactions of RISPERDAL CONSTA with coadministration of other drugs have not been systematically evaluated. The drug interaction data provided in this section is based on studies with oral RISPERDAL. Due to CNS effects, use caution when administering with other centrally-acting drugs.

Avoid alcohol. ( 7.1 ) Due to hypotensive effects, hypotensive effects of other drugs with this potential may be enhanced. ( 7.2 ) Effects of levodopa and dopamine agonists may be antagonized.

( 7.3 ) Cimetidine and ranitidine increase the bioavailability of risperidone. ( 7.5 ) Clozapine may decrease clearance of risperidone. ( 7.7 ) Fluoxetine and paroxetine increase plasma concentrations of risperidone.

( 7.12 ) Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. ( 7.13 )

7.1Centrally-Acting Drugs and Alcohol Given the primary CNS effects of risperidone, caution should be used when RISPERDAL CONSTA is administered in combination with other centrally-acting drugs or alcohol.

7.2Drugs with Hypotensive Effects Because of its potential for inducing hypotension, RISPERDAL CONSTA may enhance the hypotensive effects of other therapeutic agents with this potential.

7.3Levodopa and Dopamine Agonists RISPERDAL CONSTA may antagonize the effects of levodopa and dopamine agonists.

7.4Amitriptyline Amitriptyline did not affect the pharmacokinetics of risperidone or of risperidone and 9-hydroxyrisperidone combined following concomitant administration with oral RISPERDAL.

7.5Cimetidine and Ranitidine Cimetidine and ranitidine increased the bioavailability of oral risperidone by 64% and 26%, respectively. However, cimetidine did not affect the AUC of risperidone and 9-hydroxyrisperidone combined, whereas ranitidine increased the AUC of risperidone and 9-hydroxyrisperidone combined by 20%.

7.6Methylphenidate Concomitant use with methylphenidate, when there is change in dosage of either medication, may increase the risk of extrapyramidal symptoms (EPS). Monitor for symptoms of EPS with concomitant use of RISPERDAL CONSTA and methylphenidate [see Adverse Reactions (6.2) ] .

7.7Clozapine Chronic administration of clozapine with risperidone may decrease the clearance of risperidone.

7.8Lithium Repeated doses of oral RISPERDAL (3 mg twice daily) did not affect the exposure (AUC) or peak plasma concentrations (C max ) of lithium (N=13).

7.9Valproate Repeated doses of oral RISPERDAL (4 mg once daily) did not affect the pre-dose or average plasma concentrations and exposure (AUC) of valproate (1000 mg/day in three divided doses) compared to placebo (N=21). However, there was a 20% increase in valproate peak plasma concentration (C max ) after concomitant administration of oral RISPERDAL.

7.10Digoxin Oral RISPERDAL (0.25 mg twice daily) did not show a clinically relevant effect on the pharmacokinetics of digoxin.

7.11Topiramate Oral RISPERDAL administered at doses from 1–6 mg/day concomitantly with topiramate 400 mg/day resulted in a 23% decrease in risperidone C max and a 33% decrease in risperidone AUC 0–12 hour at steady state. Minimal reductions in the exposure to risperidone and 9-hydroxyrisperidone combined, and no change for 9-hydroxyrisperidone were observed. This interaction is unlikely to be of clinical significance.

There was no clinically relevant effect of oral RISPERDAL on the pharmacokinetics of topiramate.

7.12Drugs That Inhibit CYP 2D6 and Other CYP Isozymes Risperidone is metabolized to 9-hydroxyrisperidone by CYP 2D6, an enzyme that is polymorphic in the population and that can be inhibited by a variety of psychotropic and other drugs [see Clinical Pharmacology (12.3) ] . Drug interactions that reduce the metabolism of risperidone to 9-hydroxyrisperidone would increase the plasma concentrations of risperidone and lower the concentrations of 9-hydroxyrisperidone. Analysis of clinical studies involving a modest number of poor metabolizers (n≅70 patients) does not suggest that poor… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Renal or Hepatic Impairment: dose appropriately with oral RISPERDAL prior to initiating treatment with RISPERDAL CONSTA. A lower starting dose of RISPERDAL CONSTA of 12.5 mg may be appropriate in some patients.

( 2.4 ) Pediatric Use: safety and effectiveness not established in patients less than 18 years of age. ( 8.4 ) Elderly: dosing for otherwise healthy elderly patients is the same as for healthy nonelderly. Elderly may be more predisposed to orthostatic effects than nonelderly.

( 8.5 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including RISPERDAL CONSTA, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .

Overall, 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 maternal or fetal outcomes (see Data ). There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including RISPERDAL CONSTA, during pregnancy (see Clinical Considerations ) . Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of RISPERDAL CONSTA [see Clinical Pharmacology (12.3) ] .

The clinical significance of RISPERDAL CONSTA administered before pregnancy or anytime during pregnancy is not known. Oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (MRHD) with maternal toxicity observed at 4-times the MRHD based on mg/m 2 body surface area. Risperidone was not teratogenic in rats or rabbits at doses up to 6-times the MRHD based on mg/m 2 body surface area.

Increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the MRHD based on mg/m 2 body surface area. Learning was impaired in offspring of rats when the dams were dosed at 0.6-times the MRHD and offspring mortality increased at doses 0.1 to 3 times the MRHD based on mg/m 2 body surface area. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.

Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including RISPERDAL CONSTA, during the third trimester of pregnancy.

These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates rec… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including RISPERDAL CONSTA, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .

Overall, 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 maternal or fetal outcomes (see Data ). There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including RISPERDAL CONSTA, during pregnancy (see Clinical Considerations ) . Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of RISPERDAL CONSTA [see Clinical Pharmacology (12.3) ] .

The clinical significance of RISPERDAL CONSTA administered before pregnancy or anytime during pregnancy is not known. Oral administration of risperidone to pregnant mice caused cleft palate at doses 3 to 4 times the maximum recommended human dose (MRHD) with maternal toxicity observed at 4-times the MRHD based on mg/m 2 body surface area. Risperidone was not teratogenic in rats or rabbits at doses up to 6-times the MRHD based on mg/m 2 body surface area.

Increased stillbirths and decreased birth weight occurred after oral risperidone administration to pregnant rats at 1.5-times the MRHD based on mg/m 2 body surface area. Learning was impaired in offspring of rats when the dams were dosed at 0.6-times the MRHD and offspring mortality increased at doses 0.1 to 3 times the MRHD based on mg/m 2 body surface area. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide.

Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including RISPERDAL CONSTA, during the third trimester of pregnancy.

These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization.

Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects. A prospective observational study including 6 women treated with risperidone demonstrated placental passage of risperidone. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects.

There was… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and effectiveness of RISPERDAL CONSTA in pediatric patients have not been established. However, juvenile animal toxicology studies have been conducted with oral risperidone. Juvenile Animal Studies Juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to the period of childhood through adolescence in humans), at doses of 0.31, 1.25, or 5 mg/kg/day, which are 1.2, 3.4 and 13.5 times the MRHD of 6 mg/day for children, based on mg/m 2 body surface area.

Bone length and density were decreased with a no-effect dose of 0.31 mg/kg/day; this dose produced plasma AUC of risperidone plus its active metabolite paliperidone (9-hydroxy-risperidone) that were similar to those in children and adolescents receiving the MRHD of 6 mg/day. In addition, sexual maturation was delayed at all doses in both males and females. The above effects showed little or no reversibility in females after a 12 week drug-free recovery period.

Juvenile rats, treated with oral risperidone from days 12 to 50 of age (equivalent to the period of infancy through adolescence in humans) showed impaired learning and memory performance (reversible only in females), with a no-effect dose of 0.63 mg/kg/day which is 0.5 times the MRHD of 6 mg/day for children, based on mg/m 2 body surface area. This dose produced plasma AUC of risperidone plus paliperidone about half the exposure observed in humans at the MRHD. No other consistent effects on neurobehavioral or reproductive development were seen up to the highest tested dose of 1.25 mg/kg/day which is 1 time the MRHD and produced plasma AUC of risperidone plus paliperidone that were about two thirds of those observed in humans at the MRHD of 6 mg/day for children.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use In an open-label study, 57 clinically stable, elderly patients (≥ 65 years old) with schizophrenia or schizoaffective disorder received RISPERDAL CONSTA every 2 weeks for up to 12 months. In general, no differences in the tolerability of RISPERDAL CONSTA were observed between otherwise healthy elderly and nonelderly patients. Therefore, dosing recommendations for otherwise healthy elderly patients are the same as for nonelderly patients.

Because elderly patients exhibit a greater tendency to orthostatic hypotension than nonelderly patients, elderly patients should be instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position). In addition, monitoring of orthostatic vital signs should be considered in elderly patients for whom orthostatic hypotension is of concern [see Warnings and Precautions (5.7) ] .

Concomitant use with Furosemide in Elderly Patients with Dementia-Related Psychosis In two of four placebo-controlled trials in elderly patients with dementia-related psychosis, a higher incidence of mortality was observed in patients treated with furosemide plus oral risperidone when compared to patients treated with oral risperidone alone or with oral placebo plus furosemide. No pathological mechanism has been identified to explain this finding, and no consistent pattern for cause of death was observed. An increase of mortality in elderly patients with dementia-related psychosis was seen with the use of oral risperidone regardless of concomitant use with furosemide.

RISPERDAL CONSTA is not approved for the treatment of patients with dementia-related psychosis. [see Boxed Warning and Warnings and Precautions (5.1) ] .

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE

10.1Human Experience No cases of overdose were reported in premarketing studies with RISPERDAL CONSTA. Because RISPERDAL CONSTA is to be administered by health care professionals, the potential for overdosage by patients is low. In premarketing experience with oral RISPERDAL, there were eight reports of acute RISPERDAL overdosage, with estimated doses ranging from 20 to 300 mg and no fatalities.

In general, reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and extrapyramidal symptoms. One case, involving an estimated overdose of 240 mg, was associated with hyponatremia, hypokalemia, prolonged QT, and widened QRS. Another case, involving an estimated overdose of 36 mg, was associated with a seizure.

Postmarketing experience with oral RISPERDAL includes reports of acute overdose, with estimated doses of up to 360 mg. In general, the most frequently reported signs and symptoms are those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. Other adverse reactions reported since market introduction related to oral RISPERDAL overdose include prolonged QT interval and convulsions.

Torsade de pointes has been reported in association with combined overdose of oral RISPERDAL and paroxetine.

10.2Management of Overdosage In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of QT prolonging effects that might be additive to those of risperidone.

Similarly, it is reasonable to expect that the alpha-blocking properties of bretylium might be additive to those of risperidone, resulting in problematic hypotension. There is no specific antidote to risperidone. Therefore, appropriate supportive measures should be instituted.

The possibility of multiple drug involvement should be considered. Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of risperidone-induced alpha blockade). In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered.

Close medical supervision and monitoring should continue until the patient recovers.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism of action of risperidone in schizophrenia is unclear. The drug's therapeutic activity in schizophrenia could be mediated through a combination of dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2 ) receptor antagonism. The clinical effect from risperidone results from the combined concentrations of risperidone and its major active metabolite, 9-hydroxyrisperidone (paliperidone) [see Clinical Pharmacology (12.3) ] .

Antagonism at receptors other than D 2 and 5HT 2 may explain some of the other effects of risperidone [see Clinical Pharmacology (12.1) ] .

12.2Pharmacodynamics Risperidone is a monoaminergic antagonist with high affinity (Ki of 0.12 to 7.3 nM) for the serotonin Type 2 (5HT 2 ), dopamine Type 2 (D 2 ), α1 and α2 adrenergic, and H 1 histaminergic receptors. Risperidone showed low to moderate affinity (Ki of 47 to 253 nM) for the serotonin 5HT 1C , 5HT 1D , and 5HT 1A receptors, weak affinity (Ki of 620 to 800 nM) for the dopamine D 1 and haloperidol-sensitive sigma site, and no affinity (when tested at concentrations >10 -5 M) for cholinergic muscarinic or β1 and β2 adrenergic receptors.

12.3Pharmacokinetics Absorption After a single intramuscular (gluteal) injection of RISPERDAL CONSTA, there is a small initial release of the drug (< 1% of the dose), followed by a lag time of 3 weeks. The main release of the drug starts from 3 weeks onward, is maintained from 4 to 6 weeks, and subsides by 7 weeks following the intramuscular (IM) injection. Therefore, oral antipsychotic supplementation should be given during the first 3 weeks of treatment with RISPERDAL CONSTA to maintain therapeutic levels until the main release of risperidone from the injection site has begun [see Dosage and Administration (2) ] .

Following single doses of RISPERDAL CONSTA, the pharmacokinetics of risperidone, 9-hydroxyrisperidone (the major metabolite), and risperidone plus 9-hydroxyrisperidone were linear in the dosing range of 12.5 mg to 50 mg. The combination of the release profile and the dosage regimen (IM injections every 2 weeks) of RISPERDAL CONSTA results in sustained therapeutic concentrations. Steady-state plasma concentrations are reached after 4 injections and are maintained for 4 to 6 weeks after the last injection.

Following multiple doses of 25 mg and 50 mg RISPERDAL CONSTA, plasma concentrations of risperidone, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone were linear. Deltoid and gluteal intramuscular injections at the same doses are bioequivalent and, therefore, interchangeable. Distribution Once absorbed, risperidone is rapidly distributed.

The volume of distribution is 1–2 L/kg. In plasma, risperidone is bound to albumin and α1-acid glycoprotein. The plasma protein binding of risperidone is approximately 90%, and that of its major metabolite, 9-hydroxyrisperidone, is 77%.

Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine (100 mcg/mL), warfarin (10 mcg/mL), and carbamazepine (10 mcg/mL) caused only a slight increase in the free fraction of risperidone at 10 ng/mL and of 9-hydroxyrisperidone at 50 ng/mL, changes of unknown clinical significance. Metabolism and Drug Interactions Risperidone is extensively metabolized in the liver.

The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N-dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone.

Consequently, the clinical effect of the drug results from the combined concentrations of risperidone plus 9-hydroxyrisperidone. CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP 2D6 is subject to genetic polymorphism (about 6%–8% of Caucasians, and a very l… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 92 words ▾

12.1Mechanism of Action The mechanism of action of risperidone in schizophrenia is unclear. The drug's therapeutic activity in schizophrenia could be mediated through a combination of dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2 ) receptor antagonism. The clinical effect from risperidone results from the combined concentrations of risperidone and its major active metabolite, 9-hydroxyrisperidone (paliperidone) [see Clinical Pharmacology (12.3) ] .

Antagonism at receptors other than D 2 and 5HT 2 may explain some of the other effects of risperidone [see Clinical Pharmacology (12.1) ] .

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING RISPERDAL CONSTA ® (risperidone) is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, or 50 mg risperidone. It is provided as a single-use dose pack, consisting of a vial containing the risperidone microspheres, a pre-filled syringe containing 2 mL of diluent for RISPERDAL CONSTA, a vial adapter, and two Terumo SurGuard ® 3 Needles for intramuscular injection (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration).

12.5-mg vial/kit (NDC 50458-309-11): 41 mg (equivalent to 12.5 mg of risperidone) of a white to off-white powder provided in a vial with a violet flip-off cap (NDC 50458-309-01). 25-mg vial/kit (NDC 50458-306-11): 78 mg (equivalent to 25 mg of risperidone) of a white to off-white powder provided in a vial with a pink flip-off cap (NDC 50458-306-01). 37.5-mg vial/kit (NDC 50458-307-11): 116 mg (equivalent to 37.5 mg of risperidone) of a white to off-white powder provided in a vial with a green flip-off cap (NDC 50458-307-01).

50-mg vial/kit (NDC 50458-308-11): 152 mg (equivalent to 50 mg of risperidone) of a white to off-white powder provided in a vial with a blue flip-off cap (NDC 50458-308-01). Storage and Handling The entire dose pack should be stored in the refrigerator (36 °F to 46 °F; 2 °C to 8 °C) and protected from light. If refrigeration is unavailable, RISPERDAL CONSTA can be stored at temperatures not exceeding 77 °F (25 °C) for no more than 7 days prior to administration.

Do not expose unrefrigerated product to temperatures above 77 °F (25 °C). Keep out of reach of children.

📦 Storage and Handling 71 words ▾

Storage and Handling The entire dose pack should be stored in the refrigerator (36 °F to 46 °F; 2 °C to 8 °C) and protected from light. If refrigeration is unavailable, RISPERDAL CONSTA can be stored at temperatures not exceeding 77 °F (25 °C) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 77 °F (25 °C). Keep out of reach of children.

📋 Description ~1 min read ▾

11 DESCRIPTION RISPERDAL CONSTA ® contains risperidone, an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. The chemical designation is 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. Its molecular formula is C 23 H 27 FN 4 O 2 and its molecular weight is 410.49.

The structural formula is: Risperidone is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and

0.1N HCl. RISPERDAL CONSTA (risperidone) Long-Acting Injection is a combination of extended-release microspheres for injection and diluent for parenteral use. The extended-release microspheres formulation is a white to off-white, free-flowing powder that is available in dosage strengths of 12.5 mg, 25 mg, 37.5 mg, or 50 mg risperidone per vial.

Risperidone is micro-encapsulated in 7525 polylactide-co-glycolide (PLG) at a concentration of 381 mg risperidone per gram of microspheres. The diluent for parenteral use is a clear, colorless solution. Composition of the diluent includes 1 mg/mL citric acid anhydrous, 1.27 mg/mL disodium hydrogen phosphate dihydrate, 1 mg/mL polysorbate 20, 22.5 mg/mL sodium carboxymethyl cellulose, 6 mg/mL sodium chloride, 0.54 mg/mL sodium hydroxide, and water for injection.

The microspheres are suspended in the diluent prior to injection. RISPERDAL CONSTA is provided as a single-use dose pack, consisting of a vial containing the microspheres, a pre-filled syringe containing the diluent, a vial adapter, and two Terumo SurGuard 3 Needles (a 21 G UTW 1-inch needle with needle protection device for deltoid administration and a 20 G TW 2-inch needle with needle protection device for gluteal administration). Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Physicians are advised to discuss the following issues with patients for whom they prescribe RISPERDAL CONSTA. Neuroleptic Malignant Syndrome (NMS) Counsel patients about a potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS), that has been reported in association with administration of antipsychotic drugs. Advise patients, family members, or caregivers to contact the healthcare provider or report to the emergency room if they experience signs and symptoms of NMS, including hyperpyrexia, muscle rigidity, altered mental status including delirium, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions (5.3) ] .

Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions (5.4) ] . Metabolic Changes Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia and diabetes mellitus and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions (5.5) ] . Orthostatic Hypotension Educate patients about the risk of orthostatic hypotension and syncope, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose. [see Warnings and Precautions (5.7) ] .

Leukopenia/Neutropenia Advise patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia that they should have their CBC monitored while being treated with RISPERDAL CONSTA [see Warnings and Precautions (5.9) ] . Hyperprolactinemia Counsel patients on signs and symptoms of hyperprolactinemia that may be associated with chronic use of RISPERDAL CONSTA. Advise them to seek medical attention if they experience any of the following: amenorrhea or galactorrhea in females, erectile dysfunction or gynecomastia in males. [See Warnings and Precautions (5.6) ] .

Interference with Cognitive and Motor Performance Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery, or operating a motor vehicle, until they are reasonably certain that RISPERDAL CONSTA therapy does not affect them adversely [see Warnings and Precautions (5.10) ] . Priapism Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism [Warnings and Precautions (5.13)] .

Heat Exposure and Dehydration Counsel patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.14) ] . Concomitant Medication Advise patients to inform their healthcare providers if they are taking, or plan to take any prescription or over-the-counter drugs, as there is a potential for interactions [see Drug Interactions (7) ] . Alcohol Advise patients to avoid alcohol during treatment with RISPERDAL CONSTA [see Drug Interactions (7.1) ] .

Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with RISPERDAL CONSTA. Advise patients that RISPERDAL CONSTA may cause extrapyramidal and/or withdrawal symptoms in a neonate. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to RISPERDAL CONSTA during pregnancy [see Use in Specific Populations (8.1) ] .

Lactation Advise breastfeeding women using RISPERDAL CONSTA to monitor infants for somnolence, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) and to seek medical care if they notice these signs [see Use in Specific Populations (8.2) ] . Infertility Advise females of reproductive potential that RISPERDAL CONSTA may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversi… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption After a single intramuscular (gluteal) injection of RISPERDAL CONSTA, there is a small initial release of the drug (< 1% of the dose), followed by a lag time of 3 weeks. The main release of the drug starts from 3 weeks onward, is maintained from 4 to 6 weeks, and subsides by 7 weeks following the intramuscular (IM) injection. Therefore, oral antipsychotic supplementation should be given during the first 3 weeks of treatment with RISPERDAL CONSTA to maintain therapeutic levels until the main release of risperidone from the injection site has begun [see Dosage and Administration (2) ] .

Following single doses of RISPERDAL CONSTA, the pharmacokinetics of risperidone, 9-hydroxyrisperidone (the major metabolite), and risperidone plus 9-hydroxyrisperidone were linear in the dosing range of 12.5 mg to 50 mg. The combination of the release profile and the dosage regimen (IM injections every 2 weeks) of RISPERDAL CONSTA results in sustained therapeutic concentrations. Steady-state plasma concentrations are reached after 4 injections and are maintained for 4 to 6 weeks after the last injection.

Following multiple doses of 25 mg and 50 mg RISPERDAL CONSTA, plasma concentrations of risperidone, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone were linear. Deltoid and gluteal intramuscular injections at the same doses are bioequivalent and, therefore, interchangeable. Distribution Once absorbed, risperidone is rapidly distributed.

The volume of distribution is 1–2 L/kg. In plasma, risperidone is bound to albumin and α1-acid glycoprotein. The plasma protein binding of risperidone is approximately 90%, and that of its major metabolite, 9-hydroxyrisperidone, is 77%.

Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine (100 mcg/mL), warfarin (10 mcg/mL), and carbamazepine (10 mcg/mL) caused only a slight increase in the free fraction of risperidone at 10 ng/mL and of 9-hydroxyrisperidone at 50 ng/mL, changes of unknown clinical significance. Metabolism and Drug Interactions Risperidone is extensively metabolized in the liver.

The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. A minor metabolic pathway is through N-dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone.

Consequently, the clinical effect of the drug results from the combined concentrations of risperidone plus 9-hydroxyrisperidone. CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP 2D6 is subject to genetic polymorphism (about 6%–8% of Caucasians, and a very low percentage of Asians, have little or no activity and are "poor metabolizers") and to inhibition by a variety of substrates and some non-substrates, notably quinidine.

Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, are similar in extensive and poor metabolizers. The interactions of RISPERDAL CONSTA with coadministration of other drugs have not been systematically evaluated in human subjects.

Drug interactions are based primarily on experience with oral RISPERDAL. Risperidone could be subject to two kinds of drug-drug interactions. First, inhibitors of CYP 2D6 interfere with conversion of risperidone to 9-hydroxyrisperidone [see Drug Interactions (7.11) ] .

This occurs with quinidine, giving essentially all recipients a risperidone pharmacokinetic profile typical of poor metabolizers. The therapeutic benefits and adverse effects of RISP… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 100 words ▾

12.2Pharmacodynamics Risperidone is a monoaminergic antagonist with high affinity (Ki of 0.12 to 7.3 nM) for the serotonin Type 2 (5HT 2 ), dopamine Type 2 (D 2 ), α1 and α2 adrenergic, and H 1 histaminergic receptors. Risperidone showed low to moderate affinity (Ki of 47 to 253 nM) for the serotonin 5HT 1C , 5HT 1D , and 5HT 1A receptors, weak affinity (Ki of 620 to 800 nM) for the dopamine D 1 and haloperidol-sensitive sigma site, and no affinity (when tested at concentrations >10 -5 M) for cholinergic muscarinic or β1 and β2 adrenergic receptors.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Schizophrenia The effectiveness of RISPERDAL CONSTA in the treatment of schizophrenia was established, in part, on the basis of extrapolation from the established effectiveness of the oral formulation of risperidone. In addition, the effectiveness of RISPERDAL CONSTA in the treatment of schizophrenia was established in a 12-week, placebo-controlled trial in adult psychotic inpatients and outpatients who met the DSM-IV criteria for schizophrenia. Efficacy data were obtained from 400 patients with schizophrenia who were randomized to receive injections of 25 mg, 50 mg, or 75 mg RISPERDAL CONSTA or placebo every 2 weeks.

During a 1-week run-in period, patients were discontinued from other antipsychotics and were titrated to a dose of 4 mg oral RISPERDAL. Patients who received RISPERDAL CONSTA were given doses of oral RISPERDAL (2 mg for patients in the 25-mg group, 4 mg for patients in the 50-mg group, and 6 mg for patients in the 75-mg group) for the 3 weeks after the first injection to provide therapeutic plasma concentrations until the main release phase of risperidone from the injection site had begun. Patients who received placebo injections were given placebo tablets.

Efficacy was evaluated using the Positive and Negative Syndrome Scale (PANSS), a validated, multi-item inventory, composed of five subscales to evaluate positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. The primary efficacy variable in this trial was change from baseline to endpoint in the total PANSS score. The mean total PANSS score at baseline for schizophrenic patients in this study was 81.5.

Total PANSS scores showed significant improvement in the change from baseline to endpoint in schizophrenic patients treated with each dose of RISPERDAL CONSTA (25 mg, 50 mg, or 75 mg) compared with patients treated with placebo. While there were no statistically significant differences between the treatment effects for the three dose groups, the effect size for the 75 mg dose group was actually numerically less than that observed for the 50 mg dose group. Subgroup analyses did not indicate any differences in treatment outcome as a function of age, race, or gender.

14.2Bipolar Disorder - Monotherapy The effectiveness of RISPERDAL CONSTA for the maintenance treatment of Bipolar I Disorder was established in a multicenter, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I, who were stable on medications or experiencing an acute manic or mixed episode. A total of 501 patients were treated during a 26-week open-label period with RISPERDAL CONSTA (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg; in patients not tolerating the 25 mg dose, the dose could be reduced to 12.5 mg).

In the open-label phase, 303 (60%) patients were judged to be stable and were randomized to double-blind treatment with either the same dose of RISPERDAL CONSTA or placebo and monitored for relapse. The primary endpoint was time to relapse to any mood episode (depression, mania, hypomania, or mixed). Time to relapse was delayed in patients receiving RISPERDAL CONSTA monotherapy as compared to placebo.

The majority of relapses were due to manic rather than depressive symptoms. Based on their bipolar disorder history, subjects entering this study had had, on average, more manic episodes than depressive episodes.

14.3Bipolar Disorder - Adjunctive Therapy The effectiveness of RISPERDAL CONSTA as an adjunct to treatment with lithium or valproate for the maintenance treatment of Bipolar Disorder was established in a multi-center, randomized, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who experienced at least 4 episodes of mood disorder requiring psychiatric/clinical intervention in the previous 12 months, including at least 2 episodes in the 6 m… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence 76 words ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance RISPERDAL CONSTA (risperidone) is not a controlled substance.

9.2Abuse RISPERDAL CONSTA has not been systematically studied in animals or humans for its potential for abuse. Because RISPERDAL CONSTA is to be administered by health care professionals, the potential for misuse or abuse by patients is low.

9.3Dependence RISPERDAL CONSTA has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.

🔒 Controlled Substance 11 words ▾

9.1Controlled Substance RISPERDAL CONSTA (risperidone) is not a controlled substance.

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis - Oral Risperidone was administered in the diet at doses of 0.63, 2.5, and 10 mg/kg for 18 months to mice and for 25 months to rats. These doses are equivalent to approximately 0.2, 0.75, and 3 times (mice) and 0.4, 1.5, and 6 times (rats) the MRHD of 16 mg/day, based on mg/m 2 body surface area. A maximum tolerated dose was not achieved in male mice.

There was a significant increase in pituitary gland adenomas, endocrine pancreatic adenomas, and mammary gland adenocarcinomas. The table below summarizes the multiples of the human dose on mg/m 2 (mg/kg) basis at which these tumors occurred. Multiples of Maximum Human Dose in mg/m 2 (mg/kg) Tumor Type Species Sex Lowest Effect Level Highest No-Effect Level Pituitary adenomas mouse Female 0.75 (9.4) 0.2 (2.4) Endocrine pancreas adenomas rat Male 1.5 (9.4) 0.4 (2.4) Mammary gland adenocarcinomas mouse Female 0.2 (2.4) none rat Female 0.4 (2.4) none rat Male 6.0 (37.5) 1.5 (9.4) Mammary gland neoplasm, Total rat Male 1.5 (9.4) 0.4 (2.4) Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents.

Serum prolactin levels were not measured during the risperidone carcinogenicity studies; however, measurements during subchronic toxicity studies showed that risperidone elevated serum prolactin levels 5–6 fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unclear [see Warnings and Precautions (5.6) ] .

Carcinogenesis - Intramuscular Risperidone was evaluated in a 24-month carcinogenicity study in which SPF Wistar rats were treated every 2 weeks with intramuscular (IM) injections of either 5 mg/kg or 40 mg/kg of risperidone. These doses are 1 and 8 times the MRHD (50 mg) on a mg/m 2 basis. A control group received injections of 0.9% NaCl, and a vehicle control group was injected with placebo microspheres.

There was a significant increase in pituitary gland adenomas, endocrine pancreas adenomas, and adrenomedullary pheochromocytomas at 8 times the IM MRHD on a mg/m 2 basis. The incidence of mammary gland adenocarcinomas was significantly increased in female rats at both doses (1 and 8 times the IM MRHD on a mg/m 2 basis). A significant increase in renal tubular tumors (adenoma, adenocarcinomas) was observed in male rats at 8 times the IM MRHD on a mg/m 2 basis.

Plasma exposures (AUC) in rats were 0.3 and 2 times (at 5 and 40 mg/kg, respectively) the expected plasma exposure (AUC) at the IM MRHD. Dopamine D 2 receptor antagonists have been shown to chronically elevate prolactin levels in rodents. Serum prolactin levels were not measured during the carcinogenicity studies of oral risperidone; however, measurements taken during subchronic toxicity studies showed that oral risperidone elevated serum prolactin levels 5- to 6-fold in mice and rats at the same doses used in the oral carcinogenicity studies.

Serum prolactin levels increased in a dose-dependent manner up to 6- and 1.5-fold in male and female rats, respectively, at the end of the 24-month treatment with risperidone every 2 weeks IM. Increases in the incidence of pituitary gland, endocrine pancreas, and mammary gland neoplasms have been found in rodents after chronic administration of other antipsychotic drugs and may be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown [see Warnings and Precautions (5.6) ] .

Mutagenesis No evidence of mutagenic or clastogenic potential for risperidone was found in the in vitro tests of Ames gene mutation, the mouse lymphoma assay, rat hepatocyte DNA-repair assay, the chromosomal aberratio… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis - Oral Risperidone was administered in the diet at doses of 0.63, 2.5, and 10 mg/kg for 18 months to mice and for 25 months to rats. These doses are equivalent to approximately 0.2, 0.75, and 3 times (mice) and 0.4, 1.5, and 6 times (rats) the MRHD of 16 mg/day, based on mg/m 2 body surface area. A maximum tolerated dose was not achieved in male mice.

There was a significant increase in pituitary gland adenomas, endocrine pancreatic adenomas, and mammary gland adenocarcinomas. The table below summarizes the multiples of the human dose on mg/m 2 (mg/kg) basis at which these tumors occurred. Multiples of Maximum Human Dose in mg/m 2 (mg/kg) Tumor Type Species Sex Lowest Effect Level Highest No-Effect Level Pituitary adenomas mouse Female 0.75 (9.4) 0.2 (2.4) Endocrine pancreas adenomas rat Male 1.5 (9.4) 0.4 (2.4) Mammary gland adenocarcinomas mouse Female 0.2 (2.4) none rat Female 0.4 (2.4) none rat Male 6.0 (37.5) 1.5 (9.4) Mammary gland neoplasm, Total rat Male 1.5 (9.4) 0.4 (2.4) Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents.

Serum prolactin levels were not measured during the risperidone carcinogenicity studies; however, measurements during subchronic toxicity studies showed that risperidone elevated serum prolactin levels 5–6 fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unclear [see Warnings and Precautions (5.6) ] .

Carcinogenesis - Intramuscular Risperidone was evaluated in a 24-month carcinogenicity study in which SPF Wistar rats were treated every 2 weeks with intramuscular (IM) injections of either 5 mg/kg or 40 mg/kg of risperidone. These doses are 1 and 8 times the MRHD (50 mg) on a mg/m 2 basis. A control group received injections of 0.9% NaCl, and a vehicle control group was injected with placebo microspheres.

There was a significant increase in pituitary gland adenomas, endocrine pancreas adenomas, and adrenomedullary pheochromocytomas at 8 times the IM MRHD on a mg/m 2 basis. The incidence of mammary gland adenocarcinomas was significantly increased in female rats at both doses (1 and 8 times the IM MRHD on a mg/m 2 basis). A significant increase in renal tubular tumors (adenoma, adenocarcinomas) was observed in male rats at 8 times the IM MRHD on a mg/m 2 basis.

Plasma exposures (AUC) in rats were 0.3 and 2 times (at 5 and 40 mg/kg, respectively) the expected plasma exposure (AUC) at the IM MRHD. Dopamine D 2 receptor antagonists have been shown to chronically elevate prolactin levels in rodents. Serum prolactin levels were not measured during the carcinogenicity studies of oral risperidone; however, measurements taken during subchronic toxicity studies showed that oral risperidone elevated serum prolactin levels 5- to 6-fold in mice and rats at the same doses used in the oral carcinogenicity studies.

Serum prolactin levels increased in a dose-dependent manner up to 6- and 1.5-fold in male and female rats, respectively, at the end of the 24-month treatment with risperidone every 2 weeks IM. Increases in the incidence of pituitary gland, endocrine pancreas, and mammary gland neoplasms have been found in rodents after chronic administration of other antipsychotic drugs and may be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown [see Warnings and Precautions (5.6) ] .

Mutagenesis No evidence of mutagenic or clastogenic potential for risperidone was found in the in vitro tests of Ames gene mutation, the mouse lymphoma assay, rat hepatocyte DNA-repair assay, the chromosomal aberration test in human lymphocyte… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE RISPERDAL CONSTA ® (risperidone) Long-Acting Injection 12.5 mg, 25 mg, 37.5 mg, 50 mg For deltoid or gluteal intramuscular injection only Each injection should be administered by a healthcare professional. IMPORTANT RESOURCES For additional information, visit www.risperdalconsta.com or call Janssen Pharmaceuticals, Inc. at 1-800-526-7736. Manufactured for: Janssen Pharmaceuticals, Inc.

Titusville, NJ 08560, USA For patent information: www.janssenpatents.com © Johnson & Johnson and its affiliates 2007 Revised: 4/2025 Instructions for use RISPERDAL CONSTA ® requires close attention to these step-by-step Instructions for Use to help ensure successful administration. SINGLE-USE DEVICE Do not reuse. Medical devices require specific material characteristics to perform as intended.

These characteristics have been verified for single use only. Any attempt to re-process the device for subsequent re-use may adversely affect the integrity of the device or lead to deterioration in performance. Important Information Use components provided The components in this dose pack are specifically designed for use with RISPERDAL CONSTA ® .

RISPERDAL CONSTA ® must be reconstituted only in the diluent supplied in the dose pack. Do not substitute ANY components of the dose pack. Do not store suspension after reconstitution Administer dose as soon as possible after reconstitution to avoid settling.

Proper dosing The entire contents of the vial must be administered to ensure intended dose of RISPERDAL CONSTA ® is delivered. Dose pack contents Step 1 Assemble components Take out dose pack Connect vial adapter to vial Wait 30 minutes Remove dose pack from the refrigerator and allow to sit at room temperature for at least 30 minutes before reconstituting. Do not warm any other way.

Remove cap from vial Flip off colored cap from vial. Wipe top of the grey stopper with an alcohol swab . Allow to air dry.

Do not remove grey rubber stopper. Prepare vial adapter Hold sterile blister as shown. Peel back and remove paper backing.

Do not remove vial adapter from blister. Do not touch spike tip at any time. This will result in contamination.

Connect vial adapter to vial Place vial on a hard surface and hold by the base. Center vial adapter over the grey rubber stopper. Push vial adapter straight down onto vial top until it snaps securely into place.

Do not place vial adapter on at an angle or diluent may leak upon transfer to the vial. Connect prefilled syringe to vial adapter Remove sterile blister Keep vial vertical to prevent leakage. Hold base of vial and pull up on the sterile blister to remove.

Do not shake. Do not touch exposed luer opening on vial adapter. This will result in contamination.

Use proper grip Hold by white collar at the tip of the syringe. Do not hold syringe by the glass barrel during assembly. Remove cap Holding the white collar, snap off the white cap.

Do not twist or cut off the white cap. Do not touch syringe tip. This will result in contamination.

The broken-off cap can be discarded. Connect syringe to vial adapter Hold vial adapter by skirt to keep stationary. Hold syringe by white collar then insert tip into the luer opening of the vial adapter.

Do not hold the glass syringe barrel. This may cause the white collar to loosen or detach. Attach the syringe to the vial adapter with a firm clockwise twisting motion until it feels snug.

Do not over-tighten. Over-tightening may cause the syringe tip to break. Step 2 Reconstitute microspheres Inject diluent Inject entire amount of diluent from syringe into the vial.

Suspend microspheres in diluent Continuing to hold down the plunger rod, shake vigorously for at least 10 seconds , as shown. Check the suspension . When properly mixed, the suspension appears uniform, thick and milky in color.

Microspheres will be visible in the liquid. Immediately proceed to the next step so suspension does not settle. Transfer suspension to syringe Invert vial completely.

Slowly pull plunger… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 7 words ▾

Warnings and Precautions ( 5.6 ) 1/2025

📄 Package Label / Principal Display Panel ~2 min read ▾

PRINCIPAL DISPLAY PANEL - 12.5 mg Kit Carton 12.5 mg Dose Pack Store Package in Refrigerator (see bottom panel for storage conditions) Rx only Single use only NDC 50458-309-11 Risperdal CONSTA ® risperiDONE Long-Acting Injection DOSE PACK CONTENTS: One 12.5 mg vial of risperidone extended-release microspheres for injection One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 21-gauge UTW 1" Terumo SurGuard ® 3 safety needle for deltoid injection One 20-gauge TW 2" Terumo SurGuard ® 3 safety needle for gluteal injection Do not substitute any components of the dose pack.

For deltoid or gluteal intramuscular injection only Each injection should be administered by a healthcare professional. PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. risperdal 12.5mg

PRINCIPAL DISPLAY PANEL - 25 mg Kit Carton 25 mg Dose Pack Store Package in Refrigerator (see bottom panel for storage conditions) Rx only Single use only NDC 50458-306-11 Risperdal CONSTA ® risperiDONE Long-Acting Injection DOSE PACK CONTENTS: One 25 mg vial of risperidone extended-release microspheres for injection One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 21-gauge UTW 1" Terumo SurGuard ® 3 safety needle for deltoid injection One 20-gauge TW 2" Terumo SurGuard ® 3 safety needle for gluteal injection Do not substitute any components of the dose pack.

For deltoid or gluteal intramuscular injection only Each injection should be administered by a healthcare professional. PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. risperdal 25mg

PRINCIPAL DISPLAY PANEL - 37.5 mg Kit Carton 37.5 mg Dose Pack Store Package in Refrigerator (see bottom panel for storage conditions) Rx only Single use only NDC 50458-307-11 Risperdal CONSTA ® risperiDONE Long-Acting Injection DOSE PACK CONTENTS: One 37.5 mg vial of risperidone extended-release microspheres for injection One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 21-gauge UTW 1" Terumo SurGuard ® 3 safety needle for deltoid injection One 20-gauge TW 2" Terumo SurGuard ® 3 safety needle for gluteal injection Do not substitute any components of the dose pack.

For deltoid or gluteal intramuscular injection only Each injection should be administered by a healthcare professional. PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. risperdal 37.5mg

PRINCIPAL DISPLAY PANEL - 50 mg Kit Carton 50 mg Dose Pack Store Package in Refrigerator (see bottom panel for storage conditions) Rx only Single use only NDC 50458-308-11 Risperdal CONSTA ® risperiDONE Long-Acting Injection DOSE PACK CONTENTS: One 50 mg vial of risperidone extended-release microspheres for injection One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 21-gauge UTW 1" Terumo SurGuard ® 3 safety needle for deltoid injection One 20-gauge TW 2" Terumo SurGuard ® 3 safety needle for gluteal injection Do not substitute any components of the dose pack.

For deltoid or gluteal intramuscular injection only Each injection should be administered by a healthcare professional. PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. risperdal 50mg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
8.7K
Units reimbursed last 4 qtrs
11.2K
Gross reimbursed last 4 qtrs
$6.86M
Avg / prescription
$785.95
Avg / unit
$612.24
Latest quarter Q4 2025
1.9KRx
Medicaid pays / ea
$612.24
gross reimbursed
vs
NADAC / ea
$636.88
acquisition cost
=
Spread
−$24.6427
-4% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
58% FFS 42% MCO
Fee-for-service · 5,105 Rx Managed care · 3,622 Rx
State Medicaid map
Alaska: no data reported AK Maine: 16 units · 1.1 per 100k residents ME Washington: 98 units · 1.3 per 100k residents WA Idaho: 11 units · 0.6 per 100k residents ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 322 units · 5.6 per 100k residents MN Wisconsin: 292 units · 4.9 per 100k residents WI Michigan: 312 units · 3.1 per 100k residents MI New York: 2,299 units · 11.7 per 100k residents NY Vermont: 36 units · 5.6 per 100k residents VT New Hampshire: 48 units · 3.4 per 100k residents NH Oregon: 64 units · 1.5 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: 12 units · 1.3 per 100k residents SD Iowa: 135 units · 4.2 per 100k residents IA Illinois: 148 units · 1.2 per 100k residents IL Indiana: 129 units · 1.9 per 100k residents IN Ohio: 784 units · 6.7 per 100k residents OH Pennsylvania: 397 units · 3.1 per 100k residents PA New Jersey: 110 units · 1.2 per 100k residents NJ Massachusetts: 395 units · 5.6 per 100k residents MA California: 343 units · 0.9 per 100k residents CA Utah: 47 units · 1.4 per 100k residents UT Colorado: 56 units · 1.0 per 100k residents CO Nebraska: 27 units · 1.4 per 100k residents NE Missouri: 188 units · 3.0 per 100k residents MO Kentucky: 132 units · 2.9 per 100k residents KY West Virginia: 95 units · 5.4 per 100k residents WV Virginia: 542 units · 6.2 per 100k residents VA Maryland: 785 units · 12.7 per 100k residents MD Connecticut: 580 units · 16.0 per 100k residents CT Rhode Island: 23 units · 2.1 per 100k residents RI Arizona: 381 units · 5.1 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: 104 units · 3.4 per 100k residents AR Tennessee: 111 units · 1.6 per 100k residents TN North Carolina: 187 units · 1.7 per 100k residents NC South Carolina: 216 units · 4.0 per 100k residents SC Delaware: 27 units · 2.6 per 100k residents DE Oklahoma: no data reported OK Louisiana: 112 units · 2.4 per 100k residents LA Mississippi: 150 units · 5.1 per 100k residents MS Alabama: 245 units · 4.8 per 100k residents AL Georgia: 307 units · 2.8 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 600 units · 2.0 per 100k residents TX Florida: 338 units · 1.5 per 100k residents FL
Units reimbursed · per 100k residents
0.616.0
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Connecticut 16.0 /100k
2 Maryland 12.7 /100k
3 New York 11.7 /100k
4 Ohio 6.7 /100k
5 Virginia 6.2 /100k
6 Massachusetts 5.6 /100k
7 Minnesota 5.6 /100k
8 Vermont 5.6 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Risperdal Consta — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Risperdal Consta. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$17.93M
Claims incl. refills
12.6K
Beneficiaries
3.8K
Spend / beneficiary
$4,679.04
Spend / claim
$1,422.65
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for RISPERDAL CONSTA (this brand).

Top reported reactions

Gynaecomastia10,048
Weight Increased4,840
Drug Interaction3,316
Abnormal Weight Gain3,121
Emotional Disorder3,003
Condition Aggravated2,521
Somnolence2,402

Age at onset

Neonate115
Infant47
Child3,419
Adolescent2,014
Adult11,606
Elderly2,404

Reporter sex

74,357 reports
Male · 61%
Female · 39%
Unknown · 0%

Serious outcomes

Hospitalization26,095
Death6,604
Life-threatening4,022
Disabling2,067
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 5,327 1,889
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) ✓ Available
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Janssen Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Janssen Pharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code J2794 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 50458-0305-03 · Janssen 50458-0307-11 · Janssen →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.