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Rykindo extended-release microspheres Risperidone Kit — NDC 72526-0103-11 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Rykindo extended-release microspheres Risperidone Kit — NDC 72526-103-11 (Billing 72526-0103-11)

by Shandong Luye Pharmaceutical Co., Ltd. · 1 KIT in 1 KIT * 2 mL in 1 VIAL, SINGLE-DOSE * 2 mL in 1 SYRINGE, GLASS

This is a package of Rykindo extended-release microspheres Risperidone Kit from Shandong Luye Pharmaceutical Co., Ltd., no longer marketed (first marketed Jun 2023), no longer in the FDA NDC Directory. It is this product's only package size.

NDC 72526-0103-11
🏷️ FDA NDC (as labeled) 72526-103-11 billing pads the product segment with a zero
Rx only Brand Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 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 →

This page is curated, coded, and maintained by

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 72526-103-11 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
72526 labeler · 103 product · 11 package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 7252610311 5
FDA record last changed
Jul 24, 2026
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 72526-103-11
Product NDC 72526-103
11-digit billing NDC 72526010311
NCPDP billing unit EA — each (per item)
RxCUI 402010, 402011, 402012, 2639734, 2639736, 2639738
Application # NDA212849
SPL Set ID 58534c96-96f5-4c2e-a061-92d4506aee91
DEA schedule Non-controlled
Marketing category NDA
Marketing status Discontinued
FDA listing status Discontinued by firm
Marketing start 2023-06-20
Dosage form KIT

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

GCN Seq No 052935
GCN 20218
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 RYKINDO ER 37.5 MG VIAL KIT
FDB brand name Rykindo
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 052935
  • GCN: 20218
  • HICL (First Databank): 025509
  • AHFS class code: 28:16.08.04
  • RxCUI (RxNorm): 402010
Why two NDCs? The FDA registers this code as 72526-103-11 — 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 → 72526-0103-11. 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 RYKINDO ER 37.5 MG VIAL KIT Ingredient Risperidone Microspheres
📖 What it is MedlinePlus · NLM

Risperidone injection is used to treat schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) and bipolar I disorder (a disease that causes episodes of depression, episodes of severe mania, and other abnormal moods). Risperidone is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Read the full MedlinePlus article ↗
📗 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J2801 No ASP payment limit on file for J2801 this quarter.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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)72526-103-11
11-digit billing NDC72526-0103-11
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ2801
DescriptorINJECTION, RISPERIDONE (RYKINDO), 0.5 MG
Billing units / pkg75 units
How the units are derivedThis package is 1 EA; the HCPCS unit is 0.5 MG, so one package = 75 billing units.
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
72526-0103-11 You're viewing this Main listing 1 KIT in 1 KIT * 2 mL in 1 VIAL, SINGLE-DOSE * 2 mL in 1 SYRINGE, GLASS 2023-06-20 — Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Risperdal Consta 50458-0309-11 Janssen 1 kit $317.931 AB Availability likely —
risperidone 70748-0270-13 Lupin 1 kit $355.232 AB Availability likely —
Risperidone 00480-1232-08 Teva 1 kit $355.232 AB Availability likely —
Risperidone 00480-1342-08 Teva 1 kit $566.404 AB Availability likely —
Risperidone 70121-2627-05 Amneal 1 kit $566.404 AB Availability likely —
risperidone 70748-0271-13 Lupin 1 kit $566.404 AB Availability likely —
Risperdal Consta 50458-0306-11 Janssen 1 kit $636.878 AB Availability likely —
Risperidone 00480-1453-08 Teva 1 kit $760.218 AB Availability likely —
risperidone 70748-0272-13 Lupin 1 kit $760.218 AB Availability likely —
Risperdal Consta 50458-0307-11 Janssen 1 kit $949.938 AB Availability likely —
Risperdal Consta 50458-0308-11 Janssen 1 kit $1,273.390 AB Availability likely —
Rykindo extended-release microspheresthis 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 72526-0102-11 Shandong 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

🏛️
2023
First FDA approval
Jan 2023
📍
2026
Currently FDA-listed
3 years listed
🛡️
2032
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

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

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Apr 2032. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jan 13, 2023 RLD RS ⏳ ~5.5 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 10406161 — method of use (U-3513)
US 10406161 — method of use (U-3513)
US 10406161 — method of use (U-3513)
US 10406161 — method of use (U-3513)
US 10098882 — method of use (U-3513)
US 10098882 — method of use (U-3513)
US 10098882 — method of use (U-3513)
US 10098882 — method of use (U-3513)
US 9532991 — method of use (U-3513)
US 9532991 — method of use (U-3513)
US 9532991 — method of use (U-3513)
US 9532991 — method of use (U-3513)
US 9446135 — method of use (U-3513)
US 9446135 — method of use (U-3513)
US 9446135 — method of use (U-3513)
US 9446135 — method of use (U-3513)
US 11110094 — drug product
US 11110094 — drug product
US 11110094 — drug product
US 11110094 — drug product
2023 2025 2027 2029 2031
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (20)
PatentTypeUse codeExpires
US 10406161 ↗ Method of use U-3513 Apr 10, 2032
US 10406161 ↗ Method of use U-3513 Apr 10, 2032
US 10406161 ↗ Method of use U-3513 Apr 10, 2032
US 10406161 ↗ Method of use U-3513 Apr 10, 2032
US 10098882 ↗ Method of use U-3513 Apr 10, 2032
US 10098882 ↗ Method of use U-3513 Apr 10, 2032
US 10098882 ↗ Method of use U-3513 Apr 10, 2032
US 10098882 ↗ Method of use U-3513 Apr 10, 2032
US 9532991 ↗ Method of use U-3513 Apr 10, 2032
US 9532991 ↗ Method of use U-3513 Apr 10, 2032
US 9532991 ↗ Method of use U-3513 Apr 10, 2032
US 9532991 ↗ Method of use U-3513 Apr 10, 2032
US 9446135 ↗ Method of use U-3513 Apr 10, 2032
US 9446135 ↗ Method of use U-3513 Apr 10, 2032
US 9446135 ↗ Method of use U-3513 Apr 10, 2032
US 9446135 ↗ Method of use U-3513 Apr 10, 2032
US 11110094 ↗ Drug product — Apr 10, 2032
US 11110094 ↗ Drug product — Apr 10, 2032
US 11110094 ↗ Drug product — Apr 10, 2032
US 11110094 ↗ Drug product — Apr 10, 2032
Common questions
Is there a generic version of RYKINDO ER 37.5 MG VIAL KIT?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for RYKINDO ER 37.5 MG VIAL KIT. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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

LabelerShandong Luye Pharmaceutical Co., Ltd.
Application holderSHANDONG LUYE PHARMACEUTICAL CO LTD
FDA applicationNDA212849 (NDA)
Labeler code72526
First marketedJun 2023
Product typeHuman Prescription Drug
Portfolio9 products on file

More NDCs from Shandong Luye Pharmaceutical Co., Ltd. labeler code 72526

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 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📖 Instructions for Use 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning 91 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. RYKINDO 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. RYKINDO is not approved for use in patients with dementia-related psychosis. ( 5.1 )

🎯 Indications and Usage 73 words ▾

1 INDICATIONS AND USAGE RYKINDO is indicated: for the treatment of schizophrenia in adults as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults RYKINDO is an atypical antipsychotic indicated: for the treatment of schizophrenia in adults. ( 1 ) as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Establish tolerability with oral risperidone prior to initiating treatment with RYKINDO . ( 2.1 ) Administer RYKINDO by intramuscular (IM) injection in the gluteal muscle by a healthcare provider. Do not administer by any other route.

( 2.1 ) Recommended dosage of RYKINDO is 25 mg intramuscular (IM) every 2 weeks. Patients not responding to 25 mg may benefit from 37.5 mg or 50 mg. Dosage titration should not be made more frequently than every 4 weeks.

The maximum recommended dosage should not exceed 50 mg every 2 weeks. ( 2.2 , 2.3 ) Administer the first dose of RYKINDO along with 7 days of oral risperidone. ( 2.2 , 2.3 ) Renal or Hepatic Impairment: Titrate with oral risperidone up to at least 2 mg prior to initiating treatment with RYKINDO.

( 2.6 ) See Full Prescribing Information for important preparation and administration instructions. ( 2.8 )

2.1General Administration Information For patients who have never taken oral risperidone, establish tolerability with oral risperidone prior to initiating RYKINDO. RYKINDO should be administered every 2 weeks by intramuscular (IM) gluteal injection. Each injection should be administered by a health care professional.

Do not administer by any other route. Alternate injections between the two buttocks. Do not combine two different dose strengths of RYKINDO in a single administration.

For detailed preparation and administration instructions, see Dosage and Administration (2.8) .

2.2Dosage Recommendations for the Treatment of Schizophrenia The recommended dosage of RYKINDO for the treatment of schizophrenia is 25 mg every 2 weeks. Administer the first dose of RYKINDO along with 7 days of oral risperidone. 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. No additional benefit was observed with dosages greater than 50 mg of risperidone long-acting injection (intramuscular); however, a higher incidence of adverse reactions was observed. Dose titration should not be made more frequently than every 4 weeks.

2.3Dosage Recommendations for Maintenance Treatment of Bipolar I Disorder The recommended dosage of RYKINDO for monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder is 25 mg every 2 weeks. Administer the first dose of RYKINDO along with 7 days of oral risperidone. 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. Dose titration should not be made more frequently than every 4 weeks.

2.4Patients Currently Receiving Risperidone Long-acting Injection 2-week Intramuscular Formulation (e.g., Risperdal Consta) The RYKINDO dose for patients receiving a risperidone long-acting injection (intramuscular) every two week formulation (e.g., Risperdal Consta) should be the same as that of the previous treatment. The first injection of RYKINDO should be given 4 weeks (no later than 5 weeks) after the last injection of the previous treatment. Supplementation with oral risperidone is not recommended [see Clinical Pharmacology (12.3) ] .

Titration should not be made more frequently than every 4 weeks.

2.5Reinitiation of Treatment in Patients Previously Discontinued There are no data to specifically address reinitiation of treatment. When restarting patients who have had an interval off treatment with RYKINDO, the previously established dosage should be reinitiated if there has been no change in the patient's general medical condition. Supplementation with oral risperidone is also required.

2.6Dosage Recommendations for Patients with Renal or Hepatic Impairment Patients with renal or hepatic impairment should be treated with titrated oral risperidone prior to initiating treatment with RYKINDO [see Use in Specific Populations (8.6 , 8.7) and Clinical Pharmacology (12.3) ] . The recommended starting dose is 0.5 mg oral risperidone twice daily during the… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 84 words ▾

3 DOSAGE FORMS AND STRENGTHS RYKINDO (risperidone) for extended-release injectable suspension, for intramuscular use is available in strengths of 25 mg, 37.5 mg, and 50 mg. Each strength is provided as a single-dose kit consisting of: a vial containing a white to almost white powder, a pre-filled syringe containing 2 mL of a colorless, clear diluent, a vial adapter, and a needle (20 gauge 2-inch needle with needle protection device). For extended-release injectable suspension: 25 mg, 37.5 mg, and 50 mg.

( 3 )

⛔ Contraindications 53 words ▾

4 CONTRAINDICATIONS RYKINDO is contraindicated in patients with a known hypersensitivity to risperidone, its metabolite, paliperidone, or to any of its components. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone or paliperidone. Known hypersensitivity to risperidone, paliperidone, or to any components in RYKINDO. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased risk of cerebrovascular adverse reactions (e.g., stroke, transient ischemia attack). ( 5.2 ) Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation and close monitoring. ( 5.3 ) Tardive Dyskinesia: Discontinue treatment if clinically appropriate.

( 5.4 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.5 ) Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration. Long-standing hyperprolactinemia, when associated with hypogonadism, can lead to decreased bone density in males and females.

( 5.6 ) Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular disease or cerebrovascular disease, and risk of dehydration or syncope. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood cell counts (CBC) in patients with a history of clinically significant low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing RYKINDO if clinically significant decline in WBC occurs in the absence of other causative factors.

( 5.9 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. ( 5.11 ) Priapism: Priapism has been reported during postmarketing use of other risperidone products .

Severe priapism may require surgical intervention. ( 5.13 )

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 that was 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% versus 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.

RYKINDO is not approved for the treatment of dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.2) ] .

5.2Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73 to 97) in trials of oral risperidone in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse reactions in patients treated with oral risperidone compared to patients treated with placebo.

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

5.3Neuroleptic Malignant Syndrome (NMS) NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, m… [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 reactions, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome (NMS) [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 and syncope [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) ] Body temperature dysregulation [see Warnings and Precautions (5.14) ] Osteodystrophy and tumors in animals [see Warnings and Precautions (5.15) ] The most common adverse reactions in patients with schizophrenia (≥ 5%) were headache, parkinsonism, dizziness, akathisia, fatigue, constipation, dyspepsia, sedation, weight increase, pain in extremity, and dry mouth.

( 6 ) The most common adverse reactions in patients with bipolar disorder were (5% in monotherapy trial) weight increased and (≥ 10% in adjunctive therapy trial) tremor and parkinsonism. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Shandong Luye Pharmaceutical Co., Ltd. at 1-800-548-9765 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of RYKINDO for the treatment of schizophrenia in adults and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder in adults is based on adequate and well-controlled studies of risperidone long-acting injection (intramuscular).

The data described in this section are derived from a clinical trial database consisting of 2,392 patients exposed to one or more doses of risperidone long-acting injection (intramuscular) for the treatment of schizophrenia. Of these 2,392 patients, 332 patients received risperidone long-acting injection (intramuscular) while participating in a 12-week double-blind, placebo-controlled trial. Two hundred two (202) of the 332 were patients with schizophrenia who received 25 mg or 50 mg risperidone long-acting injection (intramuscular).

The conditions and duration of treatment with risperidone long-acting injection (intramuscular) 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. In addition to the studies in patients with schizophrenia, safety data are presented from a trial assessing the efficacy and safety of risperidone long-acting injection (intramuscular) when administered as monotherapy for maintenance treatment in patients with bipolar I disorder.

Safety data are also presented from a trial assessing the efficacy and safety of risperidone long-acting injection (intramuscular) administered as adjunctive maintenance treatment in patients with bipolar disorder (intramuscular). The most common adverse reactions in clinical trials of risperidone long-acting injection (intramuscular) in patients with schizophrenia (≥ 5%) were headache, parkinsonism, dizziness, akathisi… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): increase risperidone plasma concentration. ( 2.7 , 7.1 ) Strong CYP3A4 inducers (e.g., carbamazepine): decrease plasma concentrations of risperidone. ( 2.7 , 7.1 )

7.1Drugs Having Clinically Significant Interactions with RYKINDO The interactions of RYKINDO with co-administration of other drugs have not been studied. The drug interaction data provided in this section is based on studies with oral risperidone. Clinically significant drug interactions with RYKINDO are included in Table 7.

Table 7. Clinically Significant Drug Interactions with RYKINDO Strong CYP2D6 Inhibitors Clinical Impact Concomitant use of RYKINDO with strong CYP2D6 inhibitors may increase the plasma concentration of risperidone and lower the concentration of 9-hydroxyrisperidone, a major active metabolite of risperidone [see Clinical Pharmacology (12.3) ] . Intervention When initiation of strong CYP2D6 inhibitors is considered, patients may be placed on a lower dose of RYKINDO between 2 to 4 weeks before the planned start of strong CYP2D6 inhibitors to adjust for the expected increase in plasma concentrations of risperidone.

When a strong CYP2D6 inhibitor is initiated in patients receiving the recommended dose of 25 mg RYKINDO, it is recommended to continue treatment with the 25 mg dose unless clinical judgment necessitates either lowering the dose to 12.5 mg, in which case a different risperidone long-acting injection intramuscular formulation should be used, or interruption of RYKINDO treatment. The effects of discontinuation of strong CYP2D6 inhibitors on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied [see Dosage and Administration (2.7) ] .

Strong CYP3A4 Inducers Clinical Impact Co-administration of a strong CYP3A4 inducer with RYKINDO may cause decreases in the combined plasma concentrations of risperidone and 9-hydroxyrisperidone, which could lead to decreased efficacy of RYKINDO ® treatment [see Clinical Pharmacology (12.3) ] . Intervention When initiating therapy with a strong CYP3A4 inducer, patients should be closely monitored during the first 4 to 8 weeks because the dose of RYKINDO may need to be adjusted. A dose increase or additional oral risperidone may need to be considered.

When discontinuing a strong CYP3A4 inducer, the dosage of RYKINDO should be re-evaluated and decreased, if necessary. Patients may be placed on a lower dose of RYKINDO between 2 to 4 weeks before the planned discontinuation of CYP3A4 inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone. For patients treated with the recommended dose of 25 mg RYKINDO and discontinuing from a CYP3A4 enzyme inducer, it is recommended to continue treatment with the 25-mg dose unless clinical judgment necessitates either lowering the RYKINDO dose to 12.5 mg, in which case a different risperidone long-acting injection intramuscular formulation should be used, or interruption of RYKINDO treatment. [see Dosage and Administration (2.7) ] .

Centrally-Acting Drugs and Alcohol Clinical Impact Nervous system disorders may be exacerbated due to additive pharmacological effects associated with the concomitant use of centrally-acting drugs, including alcohol. Intervention Use caution when RYKINDO is administered in combination with other centrally-acting drugs or alcohol. Hypotensive Agents Clinical Impact Because of its potential for inducing hypotension, RYKINDO may enhance the hypotensive effects of other therapeutic agents with this potential.

Intervention Use caution when RYKINDO is administered in combination with other therapeutic agents with hypotensive effects. Dopamine Agonists Clinical Impact RYKINDO may antagonize the effects of levodopa and dopamine agonists. Intervention Caution should be used when RYKINDO is administered in combination with levodopa and dopamine agonists.

Methylphenidate Clinical Impact: Concomitant use w… [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 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including RYKINDO, 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/clinicaland-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 RYKINDO, during pregnancy (see Clinical Considerations ) . Risperidone has been detected in plasma in adult subjects up to 6 weeks after a single-dose of RYKINDO [see Clinical Pharmacology (12.3) ] .

The clinical significance of RYKINDO administered before or during pregnancy is unknown. 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 incidence of 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 the offspring of dams dosed at 0.6-times the MRHD and offspring mortality increased at maternal 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% to 4% and 15% to 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 risperidone, during the third trimester of pregnancy.

These symptoms 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 show a clear association between 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 pregnanc… [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 RYKINDO, 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/clinicaland-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 RYKINDO, during pregnancy (see Clinical Considerations ) . Risperidone has been detected in plasma in adult subjects up to 6 weeks after a single-dose of RYKINDO [see Clinical Pharmacology (12.3) ] .

The clinical significance of RYKINDO administered before or during pregnancy is unknown. 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 incidence of 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 the offspring of dams dosed at 0.6-times the MRHD and offspring mortality increased at maternal 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% to 4% and 15% to 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 risperidone, during the third trimester of pregnancy.

These symptoms 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 show a clear association between 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 a small increase in the risk of major birth defects (RR=1.26, 95… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and effectiveness of RYKINDO have not been established in pediatric patients. Juvenile Animal Toxicity Studies Juvenile dogs were treated with oral risperidone from weeks 10 to 50 of age (equivalent to childhood through adolescence in humans) at doses of 0.31, 1.25, or 5 mg/kg/day (1.2, 3.4, or 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 AUCs of risperidone and 9-hydroxyrisperidone combined 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 (0.5 times the MRHD of 6 mg/day for children).

This dose produced plasma AUCs of risperidone and 9-hydroxyrisperidone combined that were approximately half the AUCs observed in humans at the MRHD. No other consistent effects on neurobehavioral or reproductive development were seen in juvenile rats given up to the highest tested dose of 1.25 mg/kg/day which is 1 time the MRHD and produced plasma AUCs of risperidone plus paliperidone that were about two thirds of those observed in humans at the MRHD of 6mg/day of children.

🧓 Geriatric Use 179 words ▾

8.5Geriatric Use In an open-label study, 57 clinically stable, geriatric patients (≥ 65 years old) with schizophrenia or schizoaffective disorder received risperidone long-acting injection (intramuscular) every 2 weeks for up to 12 months. In general, no differences in the tolerability of risperidone long-acting injection (intramuscular) were observed between otherwise healthy geriatric and younger patients. Because geriatric patients exhibit a greater tendency for orthostatic hypotension than nonelderly patients, geriatric 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 geriatric patients for whom orthostatic hypotension is a concern [see Warnings and Precautions (5.7) ] . Elderly patients with dementia-related psychosis treated with RYKINDO are at an increased risk of death compared to placebo. RYKINDO is not approved for the treatment of patients with dementia related psychosis [see Boxed Warning and Warnings and Precautions (5.1 , 5.2) ].

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Human Experience In premarketing experience with oral risperidone, there were eight reports of acute risperidone 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 EPS. In one case, hyponatremia, hypokalemia, prolonged QT, and widened QRS were observed after a patient took an estimated 240 mg of oral risperidone.

In another case, a patient had a seizure after taking an estimated 36 mg of oral risperidone. Postmarketing experience with oral risperidone included reports of acute overdose with estimated doses up to 360 mg. In general, the most frequently reported signs and symptoms were those resulting from an exaggeration of the drug's known pharmacological effects, i.e., drowsiness, sedation, tachycardia, hypotension, and EPS.

Other postmarketing adverse reactions related to oral risperidone overdose included prolonged QT interval and convulsions. Torsade de pointes was reported in association with combined overdose of oral risperidone and paroxetine. Management of Overdosage In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation.

Cardiovascular monitoring should commence immediately and 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 implemented. 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 EPS, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

Consider contacting the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.

🧬 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 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 .

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 H1 histaminergic receptors. Risperidone shows 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 injection of RYKINDO, the release profile consists of an initial release of risperidone followed by a stable release phase of 2 to 4 weeks. The median time to peak concentration (T max ) of risperidone and 9-hydroxyrisperidone combined are 14 and 17 days after administration of 25 mg and 50 mg of RYKINDO, respectively. Systemic exposures (AUC 0-t and C max ) of the active moiety increase in a dose proportional manner across the dosing range from 25 mg to 50 mg.

The combination of the release profile and the dosage regimen (intramuscular injections every 2 weeks) of RYKINDO results in sustained concentrations within the dosing interval (every 2 weeks). Steady-state plasma concentration levels are reached after 2 injections and can be maintained for 2 to 3 weeks after the last injection. Following multiple IM injections (25 mg every two weeks for five consecutive injections) in patients, the geometric mean ratios [RYKINDO to risperidone long-acting injection (intramuscular)] of risperidone and 9-hydroxyrisperidone combined were 102.33% for the C ss-max and 94.08% for the AUC ss-tau , and the 90% CIs of the ratios were within the 80% to 125% range.

Distribution The volume of distribution of risperidone 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 the 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. Elimination Metabolism Risperidone is extensively metabolized in the liver.

The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme CYP2D6. 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. CYP2D6, also called debrisoquin hydroxylase, is responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP2D6 is subject to genetic polymorphism (about 6% to 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 CYP2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP2D6 metabolizers convert it much more slowly… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 84 words ▾

12.1Mechanism of Action The mechanism of action of risperidone in schizophrenia is unclear. The drug's therapeutic activity 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 .

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

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RYKINDO (risperidone) for extended-release injectable suspension, for intramuscular use is, when fully mixed, a white suspension, available in strengths of 25 mg, 37.5 mg, or 50 mg. It is provided as a single-dose kit, consisting of: a vial containing a white to almost white powder, a pre-filled syringe containing 2 mL of a colorless, clear diluent, a vial adapter, and a needle (a 20 gauge 2-inch needle with needle protection device). RYKINDO: 25-mg kit (NDC 72526-102-11): A white to almost white powder provided in a vial with a green flip-off cap (NDC 72526-202-01); a pre-filled syringe containing 2 mL of a colorless, clear diluent (NDC 72526-801-01); a needle; and a vial adapter.

RYKINDO: 37.5-mg kit: (NDC 72526-103-11): A white to almost white powder provided in a vial with a purple flip-off cap (NDC 72526-203-01); a pre-filled syringe containing 2 mL of a colorless, clear diluent (NDC 72526-801-01); a needle; and a vial adapter. RYKINDO 50-mg kit: (NDC 72526-104-11): A white to almost white powder provided in a vial with a blue flip-off cap (NDC 72526-204-01); a pre-filled syringe containing 2 mL of a colorless, clear diluent (NDC 72526-801-01); a needle; and a vial adapter. Storage and Handling Store kit in refrigerator at 2° to 8°C (36° to 46°F).

Protect from light. If refrigeration is unavailable, RYKINDO can be stored in its unopened original packaging at temperatures not exceeding 77°F (25°C) for no more than 7 days prior to administration. After removal from the refrigerator, use RYKINDO within 7 days or discard.

📦 Storage and Handling 57 words ▾

Storage and Handling Store kit in refrigerator at 2° to 8°C (36° to 46°F). Protect from light. If refrigeration is unavailable, RYKINDO can be stored in its unopened original packaging at temperatures not exceeding 77°F (25°C) for no more than 7 days prior to administration. After removal from the refrigerator, use RYKINDO within 7 days or discard.

📋 Description 217 words ▾

11 DESCRIPTION RYKINDO 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)piperidin-1-yl] ethyl]-2-methyl-6,7,8,9-tetrahydro-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 410.5 g/mol.

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

0.1N HCl. RYKINDO is provided as a single-dose kit consisting of: a vial containing a white to almost white powder, a pre-filled syringe containing 2 mL of a colorless, clear diluent, a vial adapter, and a needle (a 20 gauge 2-inch needle with needle protection device). The vial contains a white to almost white sterile powder containing risperidone.

The powder consists of risperidone, mannitol (5.38 mg/100 mg risperidone), polylactide-co-glycolide (PLGA) 5050 (24.2 mg/100 mg risperidone) and polylactide-co-glycolide (PLGA) 7525 (96.7 mg/100 mg risperidone). The diluent is a sterile, clear, colorless, 2 mL solution. The diluent contains: 1.10 mg/mL citric acid monohydrate, 1.02 mg/mL dibasic sodium phosphate anhydrous, 1 mg/mL polysorbate 80, 9 mg/mL sodium carboxymethyl cellulose, 7.5 mg/mL sodium chloride, 0.54 mg/mL sodium hydroxide, and water.

RYKINDO (risperidone) for extended-release injectable suspension, for intramuscular use is, when fully mixed, a white suspension, available in strengths of 25 mg, 37.5 mg, or 50 mg. Chemical Structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION 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 [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) ] . Hyperprolactinemia Counsel patients on signs and symptoms of hyperprolactinemia that may be associated with chronic use of RYKINDO. 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) ] .

Orthostatic Hypotension and Syncope 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 RYKINDO [see Warnings and Precautions (5.9) ] . Potential for Cognitive and Motor Impairment Inform patients that RYKINDO has the potential to impair judgment, thinking, or motor skills.

Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that treatment with RYKINDO 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 [see Warnings and Precautions (5.13) ] .

Heat Exposure and Dehydration Educate 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, since there is a potential for interactions [see Drug Interactions (7) ] . Alcohol Advise patients to avoid alcohol during treatment with RYKINDO [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 RYKINDO. Advise patients that RYKINDO may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in a neonate. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to RYKINDO during pregnancy [see Use in Specific Populations (8.1) ].

Lactation Advise breastfeeding women using RYKINDO to monitor infants for somnolence, failure to thrive, jitteriness, and EPS (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 RYKINDO may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible [see Use in Specific Populations (8.3) ].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption After a single intramuscular injection of RYKINDO, the release profile consists of an initial release of risperidone followed by a stable release phase of 2 to 4 weeks. The median time to peak concentration (T max ) of risperidone and 9-hydroxyrisperidone combined are 14 and 17 days after administration of 25 mg and 50 mg of RYKINDO, respectively. Systemic exposures (AUC 0-t and C max ) of the active moiety increase in a dose proportional manner across the dosing range from 25 mg to 50 mg.

The combination of the release profile and the dosage regimen (intramuscular injections every 2 weeks) of RYKINDO results in sustained concentrations within the dosing interval (every 2 weeks). Steady-state plasma concentration levels are reached after 2 injections and can be maintained for 2 to 3 weeks after the last injection. Following multiple IM injections (25 mg every two weeks for five consecutive injections) in patients, the geometric mean ratios [RYKINDO to risperidone long-acting injection (intramuscular)] of risperidone and 9-hydroxyrisperidone combined were 102.33% for the C ss-max and 94.08% for the AUC ss-tau , and the 90% CIs of the ratios were within the 80% to 125% range.

Distribution The volume of distribution of risperidone 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 the 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. Elimination Metabolism Risperidone is extensively metabolized in the liver.

The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme CYP2D6. 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. CYP2D6, also called debrisoquin hydroxylase, is responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. CYP2D6 is subject to genetic polymorphism (about 6% to 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 CYP2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP2D6 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. Excretion Risperidone and its metabolites are eliminated via the urine and, to a much lesser extent, via the feces.

In a mass balance study of a single 1 mg oral dose of 14 C-risperidone administered in solution to three healthy male volunteers, total recovery of radioactivity at 1 week was 84%, including 70% in the urine and 14% in the feces. The apparent half-life (t ½ ) of active moiety following RYKINDO administration is 3 to 6 days and associated with a monoexponential decline in plasma concentrations after a single dose. This t ½ is related to the erosion of the sterile powder and subsequent absorption of risperidone after RYKINDO intramuscular administration.

The clearance of risperidone and risperidone plus 9-hydroxyrisperidone was

13.7 L/h and

5.0 L/h in extensive CYP2D6 metabolizers, and

3.3 L/h and

3.2L/h in poor CYP 2D6… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 99 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 H1 histaminergic receptors. Risperidone shows 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 RYKINDO in the treatment of schizophrenia is based on an adequate and well-controlled study with risperidone long-acting injection (intramuscular). The effectiveness of risperidone long-acting injection (intramuscular) was established, in part, on the basis of the established effectiveness of the oral formulation of risperidone as well as in a 12-week, placebo-controlled trial in adult inpatients and outpatients who met the DSM-IV criteria for schizophrenia. The results of the adequate and well-controlled study are presented below.

Efficacy data were obtained from 400 patients with schizophrenia who were randomized to receive injections of 25 mg, 50 mg, or 75 mg risperidone long-acting injection (intramuscular) 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 risperidone. Patients who received risperidone long-acting injection (intramuscular) were given doses of oral risperidone (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 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 risperidone long-acting injection (intramuscular) (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 RYKINDO for the maintenance treatment of bipolar I disorder is based on an adequate and well-controlled study with risperidone long-acting injection (intramuscular). The efficacy of risperidone long-acting injection (intramuscular) 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. The results of the adequate and well-controlled study are presented below.

A total of 501 patients were treated during a 26-week open-label period with the risperidone long-acting injection (intramuscular) (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 risperidone long-acting injection (intramuscular) 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 risperidone long-acting injection (intramuscular) monotherapy compared with patients receiving placebo. The majority of relapses were due to manic rather than depressive symptoms.

Based on their bipolar disorder history, subjects entering this… [Excerpted — this section continues on DailyMed.]

🧪 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. Table 8 summarizes the multiples of the human dose on a mg/m 2 (mg/kg) basis at which these tumors occurred. Table 8.

Summary of Tumor Occurrence at Multiples of the MRHD MRHD = maximum recommended human dose on a mg/ m 2 (mg/kg) basis with Oral Risperidone Dosing in Mice and Rats Tumor Type Species Sex Multiples of the MRHD in mg/m 2 (mg/kg) 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 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 by 5- to 6- fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms were found in rodents after chronic administration of other antipsychotic drugs. These neoplasms were considered to be prolactin-mediated.

The clinical relevance 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. 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 by 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 risperidon… [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. Table 8 summarizes the multiples of the human dose on a mg/m 2 (mg/kg) basis at which these tumors occurred. Table 8.

Summary of Tumor Occurrence at Multiples of the MRHD MRHD = maximum recommended human dose on a mg/ m 2 (mg/kg) basis with Oral Risperidone Dosing in Mice and Rats Tumor Type Species Sex Multiples of the MRHD in mg/m 2 (mg/kg) 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 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 by 5- to 6- fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms were found in rodents after chronic administration of other antipsychotic drugs. These neoplasms were considered to be prolactin-mediated.

The clinical relevance 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. 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 by 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 vitr… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE RYKINDO ® [ray-KIN-do] (risperidone) injection, for gluteal intramuscular use This Instruction for Use contains information on how to inject RYKINDO ® Important Information You Need to Know Before Injecting RYKINDO ® • For gluteal intramuscular injection use only For gluteal intramuscular injection only. Do not inject by any other route. Alternate injections between the two buttocks. • Wait 30 minutes Remove dose pack from the refrigerator and allow to sit at room temperature for at least 30 minutes prior to preparation.

Do not warm any other way. Prepare medication when you are ready to administer the dose. • Use components provided The components in this dose pack are specifically designed for use with RYKINDO. RYKINDO 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 the intended dose of RYKINDO is delivered. • Do not reuse. RYKINDO ® is for one-time use only.

Do not reuse RYKINDO. The components of the single-dose kit are shown in Figure 1. Figure1: Single-dose Kit Components Preparing to Inject RYKINDO ® Step 1.

Take out kit and 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 gray stopper with an alcohol swab. Allow to air dry. Do not remove gray 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 gray 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.

Step 2. 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 the LUER-LOK ADAPTER at the tip of the syringe. Do not hold syringe by the glass barrel during assembly. Remove cap Holding the transparent LUER-LOK ADAPTER, unscrew the translucent gray cap.

Do not snap or cut off the translucent gray cap. Do not touch syringe tip. This will result in contamination.

The unscrewed cap can be discarded. Connect syringe to vial adapter Hold vial adapter by skirt to keep stationary. Hold syringe by the LUER-LOK ADAPTER then turn it to connect with the luer opening of the vial adapter.

Do not hold the glass syringe barrel. This may cause the LUER-LOK ADAPTER 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 3.

Reconstitute powder Inject diluent Inject entire amount of diluent from syringe into the vial. Suspend powder in diluent Continuing to hold down the plunger rod, shake vigorously for at least 30 seconds , as shown. Check the suspension.

When properly mixed, the suspension appears uniform, thick and milky in color. Immediately proceed to the next step so suspension does not settle. Transfer suspension to syringe Invert vial completely.

Slowly pull plunger rod down to withdraw entire contents from the vial into the syringe. Remove vial adapter Hold the LUER-LOK ADAPTER on the syringe and unscrew from vial adapter. Tear section of the vial label at the perforation.

Apply detached label to the syringe fo… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 9 words ▾

Dosage and Administration ( 2.6 , 2.7 ) 1/2026

📄 Package Label / Principal Display Panel ~1 min read ▾

PRINCIPAL DISPLAY PANEL - 25 mg Kit Carton 25 mg Kit Rykindo ® (risperiDONE) for extended-release injectable suspension KIT CONTENTS: One 25 mg vial of risperiDONE for extended-release injectable suspension One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 20-gauge 2-inch safety needle for gluteal intramuscular injection only Do not substitute any components of the kit. For gluteal intramuscular injection only. Each injection should be administered by a healthcare professional.

Rx only Single dose Store Kit in Refrigerator (see bottom panel for storage conditions) PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. NDC 72526-102-11 Principal Display Panel - 25 mg Kit Carton

PRINCIPAL DISPLAY PANEL - 37.5 mg Kit Carton 37.5 mg Kit Rykindo ® (risperiDONE) for extended-release injectable suspension KIT CONTENTS: One 37.5 mg vial of risperiDONE for extended-release injectable suspension One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 20-gauge 2-inch safety needle for gluteal intramuscular injection only Do not substitute any components of the kit. For gluteal intramuscular injection only. Each injection should be administered by a healthcare professional.

Rx only Single dose Store Kit in Refrigerator (see bottom panel for storage conditions) PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. NDC 72526-103-11 Principal Display Panel - 37.5 mg Kit Carton

PRINCIPAL DISPLAY PANEL - 50 mg Kit Carton 50 mg Kit Rykindo ® (risperiDONE) for extended-release injectable suspension KIT CONTENTS: One 50 mg vial of risperiDONE for extended-release injectable suspension One pre-filled syringe containing 2 mL of diluent One Vial Adapter One 20-gauge 2-inch safety needle for gluteal intramuscular injection only Do not substitute any components of the kit. For gluteal intramuscular injection only. Each injection should be administered by a healthcare professional.

Rx only Single dose Store Kit in Refrigerator (see bottom panel for storage conditions) PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE. NDC 72526-104-11 Principal Display Panel - 50 mg Kit Carton

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

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

Medicare Part D (outpatient prescription) spending for Uzedy (matched by generic name) — 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 Uzedy. CMS lists 5 products for this generic; we show the highest-spend one. 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
$49.48M
Claims incl. refills
14K
Beneficiaries
6.5K
Spend / beneficiary
$7,584.84
Spend / claim
$3,535.76
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.

About this NDC listing & data coverage

Finished prescription product Kit / multi-component package No longer marketed (per FDA listing data)

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) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“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

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
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.
Who lists this product with the FDA?
Shandong Luye Pharmaceutical Co., Ltd. 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 J2801 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.
← 72526-0102-11 · Shandong 72526-0104-11 · Shandong →
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.