INVEGA SUSTENNA paliperidone palmitate 234 mg/1.5mL Injection, 1 syringe — NDC 50458-564-01 (Billing 50458-0564-01)
This is a package of 1 syringe of INVEGA SUSTENNA paliperidone palmitate 234 mg/1.5mL Injection from Janssen Pharmaceuticals, Inc., marketed since Jul 2009 and currently FDA-listed; retail pharmacies pay about $2,338.47 per mL (NADAC). It is the main listing for this product, which comes in 2 package sizes.
NDC database record
One package, one record: these facts belong to NDC 50458-564-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 50458 labeler · 564 product · 01 package
- Package marketed since
- Jul 31, 2009
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2026
- Barcode (UPC-A, from the NDC)
- 3 5045856401 3
- Medicaid fills, this package
- 372,926 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 065452
- GCN: 27418
- GPI-14 (Medi-Span): 5907005010E638
- HICL (First Databank): 036479
- AHFS class code: 28:16.08.04
- RxCUI (RxNorm): 858048
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 8, 2026
RxNorm drug class
This medicine belongs to the Atypical Antipsychotic class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It treats schizophrenia in adults. Invega Hafyera is given every six months after you have been stable on a monthly or three-monthly injection. Invega Sustenna dosing also covers s...
- No. A healthcare professional must give every injection into a muscle. Keep your appointments, and call your clinic if you miss one so they can tell you how to catch up.
- Common ones are injection site soreness, sleepiness, dizziness, restlessness and movement stiffness. Weight gain and headache can also occur. Tell your care team if they bother you...
- Call for high fever with severe stiffness or confusion, fainting, a racing heartbeat, seizures, or uncontrolled movements. Also call for stroke signs or a painful erection that won...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Paliperidone Palmitate — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
Ask a licensed pharmacist directly — free, answered by our team.
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 system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $2,338.470 | $3,507.71 / 1.5 ml |
| Medicaid paysCMS SDUD · 12 mo | $2,273.44 | $3,410.15 / 1.5 ml |
| Medicare drug plans payPart D · Q2 2026 | $2,374.67 | $3,562.01 / 1.5 ml |
| Medicare Part B allowsASP · J2426 | $15.431 / J2426 unit | — |
Where does this data come from?
- CMS NADAC weekly file · file of Oct 7, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Billing & reimbursement
Where does this data come from?
- CMS ASP NDC-HCPCS crosswalk · refreshed Sep 22, 2026
- DMEPDAC NDC-HCPCS crosswalk
- openFDA NSDE billing units · refreshed Oct 7, 2026
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 50458-0564-01 You're viewing this Main listing | 1 SYRINGE in 1 KIT / 1.5 mL in 1 SYRINGE | $2,338.47 / mL | $3,507.71 | 2009-07-31 | — | Active |
| 50458-0564-03 50458-564-03 | 1 SYRINGE in 1 KIT / 1.5 mL in 1 SYRINGE Sample | — | — | 2009-07-31 | — | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 50458-0564-03?
What NDC number is used to bill for this package of INVEGA SUSTENNA paliperidone palmitate 234 mg/1.5mL Injection?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Invega Sustenna 234 mg/1.5mLthis 50458-0564-01 | Janssen | 1 syringe | $2,338.470 | — | Availability likely | — |
| Erzofri extended-release 234 mg/1.5mL 72526-0109-11 | Shandong | 1 syringe | — | — | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Oct 7, 2026
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
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.
🛈 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.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9439906 ↗ | Method of use | U-2758 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2757 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2757 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2758 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2758 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2757 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2757 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2758 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2758 | Jan 26, 2031 |
| US 9439906 ↗ | Method of use | U-2757 | Jan 26, 2031 |
Is there a generic version of INVEGA SUSTENNA 234 MG/1.5 ML?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
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 Paliperidone Injection 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
-
UNII 4R4HFI6D95
Polyethylene glycol 4000 is a synthetic polymer derived from petroleum. It serves as a binder, filler, and lubricant in solid dosage forms, and helps control how quickly the medicine dissolves.
-
UNII 7T1F30V5YH
A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
-
UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
-
UNII 22ADO53M6F
A mineral salt derived from phosphoric acid, used as a buffer to maintain the pH balance of the medication and help stabilize the active ingredients.
-
UNII 3980JIH2SW
A salt form of phosphoric acid that acts as a buffer and pH adjuster in medicines. It helps keep the product at the correct acidity level for stability and effectiveness.
-
UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
7 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 8, 2026
- FDA openFDA NDC Directory · synced Oct 8, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Janssen Pharmaceuticals, Inc. labeler code 50458
- Invega paliperidone 9 mg Tablet, Extended Release NDC 50458-552-01
- Invega paliperidone 1.5 mg Tablet, Extended Release NDC 50458-554-01
- INVEGA SUSTENNA paliperidone palmitate 39 mg/.25mL Injection NDC 50458-560-01
- INVEGA SUSTENNA paliperidone palmitate 78 mg/.5mL Injection NDC 50458-561-01
- INVEGA SUSTENNA paliperidone palmitate 117 mg/.75mL Injection NDC 50458-562-01
- INVEGA SUSTENNA paliperidone palmitate 156 mg/mL Injection NDC 50458-563-01
- Xarelto rivaroxaban 155 mg Granule, For Suspension NDC 50458-575-01
- Xarelto rivaroxaban 2.5 mg Tablet, Film Coated NDC 50458-577-10
- Xarelto rivaroxaban 15 mg Tablet, Film Coated NDC 50458-578-07
- Xarelto rivaroxaban 20 mg Tablet, Film Coated NDC 50458-579-07
- Xarelto rivaroxaban 10 mg Tablet, Film Coated NDC 50458-580-07
- XARELTO Rivaroxaban Kit NDC 50458-584-51
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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. INVEGA SUSTENNA is not approved for use in 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. INVEGA SUSTENNA is not approved for use in patients with dementia-related psychosis. ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE INVEGA SUSTENNA (paliperidone palmitate) is indicated for the treatment of: Schizophrenia in adults [see Clinical Studies (14.1) ]. Schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants [see Clinical Studies (14.2) ]. INVEGA SUSTENNA is an atypical antipsychotic indicated for Treatment of schizophrenia in adults.
( 1 ) Treatment of schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For intramuscular injection only. ( 2.1 ) Each injection must be administered only by a healthcare professional. ( 2.1 ) For deltoid injection, use 1-inch 23G needle for patients weighing less than 90 kg or 1½-inch 22G needle for patients weighing 90 kg or more.
For gluteal injection, use 1½-inch 22G needle regardless of patient weight. ( 2.1 ) Indication Initiation Dosing (deltoid) Monthly Maintenance Dose Administered 5 weeks after the first injection. (deltoid or gluteal) Maximum Monthly Dose Day 1 Day 8 Schizophrenia ( 2.2 ) 234 mg 156 mg 39–234 mg The recommended maintenance dose for treatment of schizophrenia is 117 mg.
Some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). 234 mg Schizoaffective disorder ( 2.2 ) 234 mg 156 mg 78–234 mg Adjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not studied in the long-term schizoaffective disorder study.
234 mg For patients naïve to oral paliperidone or oral or injectable risperidone, establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA. ( 2.2 ) Missed Doses: To manage either a missed second initiation dose or a missed monthly maintenance dose, refer to the Full Prescribing Information. ( 2.3 ) Moderate to severe renal impairment (creatinine clearance < 50 mL/min): INVEGA SUSTENNA is not recommended.
( 2.5 ) Mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min): Administer 156 mg on treatment Day 1 and 117 mg on Day 8, both in the deltoid muscle. Follow with the recommended monthly maintenance dose of 78 mg, administered in the deltoid or gluteal muscle. Adjust monthly maintenance dose based on tolerability and/or efficacy within the strengths of 39 mg, 78 mg, 117 mg, or 156 mg.
The maximum monthly dose is 156 mg for patients with mild renal impairment. ( 2.5 )
2.1Administration Instructions Each injection must be administered only by a healthcare professional. Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration, whenever product and container permit. INVEGA SUSTENNA is intended for intramuscular use only.
Do not administer by any other route. Avoid inadvertent injection into a blood vessel. Administer the dose in a single injection; do not administer the dose in divided injections.
Inject slowly, deep into the deltoid or gluteal muscle. INVEGA SUSTENNA must be administered using only the needles that are provided in the INVEGA SUSTENNA kit. The recommended needle size for administration of INVEGA SUSTENNA into the deltoid muscle is determined by the patient's weight: For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended. Deltoid injections should be alternated between the two deltoid muscles. The recommended needle size for administration of INVEGA SUSTENNA into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.
Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.
2.2Schizophrenia and Schizoaffective Disorder For patients who have never taken oral paliperidone or oral or injectable risperidone, it is recommended to establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA. The recommended dosing of INVEGA SUSTENNA for each approved indication is displayed in Table 1. The recommended initiation of INVEGA SUSTENNA is with a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle.
Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle. Table 1: Recommended Dosing of INVEGA SUSTENNA for… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS INVEGA SUSTENNA is available as a white to off-white aqueous extended-release injectable suspension for intramuscular injection in dose strengths of 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/mL, and 234 mg/1.5 mL paliperidone palmitate in single-dose prefilled syringes. Extended-release injectable suspension: 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/mL, or 234 mg/1.5 mL ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS INVEGA SUSTENNA is contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the INVEGA SUSTENNA formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. Paliperidone palmitate is converted to paliperidone, which is a metabolite of risperidone.
Known hypersensitivity to paliperidone, risperidone, or to any excipients in INVEGA SUSTENNA. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g. stroke, transient ischemic attack). ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring. ( 5.3 ) QT Prolongation: Avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval.
( 5.4 ) Tardive Dyskinesia: Discontinue drug if clinically appropriate. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. ( 5.6 ) Orthostatic Hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing INVEGA SUSTENNA if clinically significant decline in WBC in the absence of other causative factors. ( 5.9 ) Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration.
( 5.10 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.11 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.12 )
5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
INVEGA SUSTENNA is not approved for the treatment of patients with 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 In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. No studies have been conducted with oral paliperidone, INVEGA SUSTENNA, or the 3-month paliperidone palmitate extended-release injectable suspension in elderly patients with dementia.
These medicines are not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] .
5.3Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex, has been reported in association with antipsychotic drugs, including paliperidone. 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, myoglobinur… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
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 [see Warnings and Precautions (5.3) ] QT prolongation [see Warnings and Precautions (5.4) ] Tardive dyskinesia [see Warnings and Precautions (5.5) ] Metabolic changes [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) ] Hyperprolactinemia [see Warnings and Precautions (5.10) ] Potential for cognitive and motor impairment [see Warnings and Precautions (5.11) ] Seizures [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Priapism [see Warnings and Precautions (5.14) ] Disruption of body temperature regulation [see Warnings and Precautions (5.15) ] The most common adverse reactions (incidence ≥ 5% and occurring at least twice as often as placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia, and extrapyramidal disorder.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-526-7736 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. Patient Exposure The data described in this section are derived from a clinical trial database consisting of a total of 3817 subjects (approximately 1705 patient-years exposure) with schizophrenia who received at least one dose of INVEGA SUSTENNA in the recommended dose range of 39 mg to 234 mg and a total of 510 subjects with schizophrenia who received placebo.
Among the 3817 INVEGA SUSTENNA-treated subjects, 1293 received INVEGA SUSTENNA in four fixed-dose, double-blind, placebo-controlled trials (one 9-week and three 13-week studies), 849 received INVEGA SUSTENNA in the maintenance trial (median exposure 229 days during the initial 33-week open-label phase of this study, of whom 205 continued to receive INVEGA SUSTENNA during the double-blind placebo-controlled phase of this study [median exposure 171 days]), and 1675 received INVEGA SUSTENNA in five non-placebo controlled trials (three noninferiority active-comparator trials, one long-term open-label pharmacokinetic and safety study, and an injection site [deltoid-gluteal] cross-over trial).
One of the 13-week studies included a 234 mg INVEGA SUSTENNA initiation dose followed by treatment with either 39 mg, 156 mg, or 234 mg every 4 weeks. The safety of INVEGA SUSTENNA was also evaluated in a 15-month, long-term study comparing INVEGA SUSTENNA to selected oral antipsychotic therapies in adult subjects with schizophrenia. A total of 226 subjects received INVEGA SUSTENNA during the 15-month, open-label period of this study; 218 subjects received selected oral antipsychotic therapies.
The safety of INVEGA SUSTENNA was similar to that seen in previous double-blind, placebo-controlled clinical trials in adult subjects with schizophrenia. The safety of INVEGA SUSTENNA was also evaluated in a long-term study in adult subjects with schizoaffective disorder. A total of 667 subjects received INVEGA SUSTENNA during the initial 25-week open-label period of this study (median exposure 147 days); 164 subjects continued to receive INVEGA SUSTENNA during the 15-month double-blind placebo-controlled period of this study (median exposure 446 days).
Adverse reactions that occurred more frequently… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Drugs that may cause orthostatic hypotension: An additive effect may occur when co-administered with INVEGA SUSTENNA. ( 7.1 ) Strong CYP3A4/P-glycoprotein (P-gp) inducers : Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John's Wort) during a dosing interval for INVEGA SUSTENNA. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended-release tablets.
( 2.5 , 7.1 , 12.3 )
7.1Drugs Having Clinically Important Interactions with INVEGA SUSTENNA Because paliperidone palmitate is hydrolyzed to paliperidone [see Clinical Pharmacology (12.3) ] , results from studies with oral paliperidone should be taken into consideration when assessing drug-drug interaction potential. Table 13. Clinically Important Drug Interactions with INVEGA SUSTENNA Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Centrally Acting Drugs and Alcohol Given the primary CNS effects of paliperidone, concomitant use of centrally acting drugs and alcohol may modulate the CNS effects of INVEGA SUSTENNA.
INVEGA SUSTENNA should be used with caution in combination with other centrally acting drugs and alcohol [see Adverse Reactions (6.1 , 6.2) ] . Drugs with Potential for Inducing Orthostatic Hypotension Because INVEGA SUSTENNA has the potential for inducing orthostatic hypotension, an additive effect may occur when INVEGA SUSTENNA is administered with other therapeutic agents that have this potential [see Warnings and Precautions (5.7) ] . Monitor orthostatic vital signs in patients who are vulnerable to hypotension [see Warnings and Precautions (5.7) ] .
Strong Inducers of CYP3A4 and P-gp (e.g., carbamazepine, rifampin, or St. John's Wort) The concomitant use of paliperidone and strong inducers of CYP3A4 and P-gp may decrease the exposure of paliperidone [see Clinical Pharmacology (12.3) ] . Avoid using CYP3A4 and/or P-gp inducers with INVEGA SUSTENNA during the 1-month dosing interval, if possible.
If administering a strong inducer is necessary, consider managing the patient using paliperidone extended-release tablets [see Dosage and Administration (2.5) ] . Levodopa and Other Dopamine Agonists Paliperidone may antagonize the effect of levodopa and other dopamine agonists. Monitor and manage patient as clinically appropriate.
7.2Drugs Having No Clinically Important Interactions with INVEGA SUSTENNA Clinically meaningful pharmacokinetic interaction between INVEGA SUSTENNA and valproate (including valproic acid and divalproex sodium) is not expected. Based on pharmacokinetic studies with oral paliperidone, no dosage adjustment of INVEGA SUSTENNA is required when administered with valproate [see Clinical Pharmacology (12.3) ]. Additionally, no dosage adjustment is necessary for valproate when co-administered with INVEGA SUSTENNA [See Clinical Pharmacology (12.3) ].
Pharmacokinetic interaction between lithium and INVEGA SUSTENNA is also unlikely. Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes. In vitro studies indicate that CYP2D6 and CYP3A4 may be involved in paliperidone metabolism; however, there is no evidence in vivo that inhibitors of these enzymes significantly affect the metabolism of paliperidone.
Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19; an interaction with inhibitors or inducers of these isozymes is unlikely. [see Clinical Pharmacology (12.3) ]
👥 Use in Specific Populations ▾
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 INVEGA SUSTENNA, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .
Overall, available data from published epidemiologic studies of pregnant women exposed to paliperidone have not established a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including INVEGA SUSTENNA, during pregnancy (see Clinical Considerations ). Paliperidone has been detected in plasma in adult subjects up to 126 days after a single-dose administration of INVEGA SUSTENNA [see Clinical Pharmacology (12.3) ] , and the clinical significance of INVEGA SUSTENNA administered before pregnancy or anytime during pregnancy is not known.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
In animal reproduction studies, there were no treatment related effects on the offspring when pregnant rats were injected intramuscularly with paliperidone palmitate during the period of organogenesis at doses up to 10 times the maximum recommended human dose (MRHD) of 234 mg paliperidone based on mg/m 2 body surface area. There were no increases in fetal abnormalities when pregnant rats and rabbits were treated orally with paliperidone during the period of organogenesis with up to 8 times the MRHD of 12 mg of paliperidone based on mg/m 2 body surface area.
Additional reproduction toxicity studies were conducted with orally administered risperidone, which is extensively converted to paliperidone (see Animal data ). Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, 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 INVEGA SUSTENNA, during the third trimester of pregnancy. These symptoms have varied in severity.
Monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A prospective observational study including 6 women treated with risperidone, the parent compound of paliperidone, demonstrated placental passage of risperidone and paliperidone. A… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including INVEGA SUSTENNA, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations ) .
Overall, available data from published epidemiologic studies of pregnant women exposed to paliperidone have not established a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, including INVEGA SUSTENNA, during pregnancy (see Clinical Considerations ). Paliperidone has been detected in plasma in adult subjects up to 126 days after a single-dose administration of INVEGA SUSTENNA [see Clinical Pharmacology (12.3) ] , and the clinical significance of INVEGA SUSTENNA administered before pregnancy or anytime during pregnancy is not known.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
In animal reproduction studies, there were no treatment related effects on the offspring when pregnant rats were injected intramuscularly with paliperidone palmitate during the period of organogenesis at doses up to 10 times the maximum recommended human dose (MRHD) of 234 mg paliperidone based on mg/m 2 body surface area. There were no increases in fetal abnormalities when pregnant rats and rabbits were treated orally with paliperidone during the period of organogenesis with up to 8 times the MRHD of 12 mg of paliperidone based on mg/m 2 body surface area.
Additional reproduction toxicity studies were conducted with orally administered risperidone, which is extensively converted to paliperidone (see Animal data ). Clinical Considerations Disease-associated maternal and/or embryo/fetal risk There is a risk to the mother from untreated schizophrenia, 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 INVEGA SUSTENNA, during the third trimester of pregnancy. These symptoms have varied in severity.
Monitor neonates exhibiting extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A prospective observational study including 6 women treated with risperidone, the parent compound of paliperidone, demonstrated placental passage of risperidone and paliperidone. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increa… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of INVEGA SUSTENNA in patients < 18 years of age have not been established. Juvenile Animal Studies In a study in which juvenile rats were treated with oral paliperidone from days 24 to 73 of age, a reversible impairment of performance in a test of learning and memory was seen, in females only, with a no-effect dose of 0.63 mg/kg/day, which produced plasma levels (AUC) of paliperidone similar to those in adolescents dosed at 12 mg/day. No other consistent effects on neurobehavioral or reproductive development were seen up to the highest dose tested (2.5 mg/kg/day), which produced plasma levels of paliperidone 2–3 times those in adolescents.
Juvenile dogs were treated for 40 weeks with oral risperidone, which is extensively metabolized to paliperidone in animals and humans, at doses of 0.31, 1.25, or 5 mg/kg/day. Decreased bone length and density were seen with a no-effect dose of 0.31 mg/kg/day, which produced plasma levels (AUC) of risperidone plus paliperidone which were similar to those in children and adolescents receiving the MRHD of risperidone. In addition, a delay in sexual maturation was seen 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. The long-term effects of INVEGA SUSTENNA on growth and sexual maturation have not been fully evaluated in children and adolescents.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of INVEGA SUSTENNA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. This drug is known to be substantially excreted by the kidney and clearance is decreased in patients with renal impairment [see Clinical Pharmacology (12.3) ] , who should be given reduced doses.
Because elderly patients are more likely to have decreased renal function, adjust dose based on renal function [see Dosage and Administration (2.5) ].
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Human Experience No cases of overdose were reported in premarketing studies with INVEGA SUSTENNA. Because INVEGA SUSTENNA is to be administered by healthcare professionals, the potential for overdosage by patients is low. While experience with paliperidone overdose is limited, among the few cases of overdose reported in premarketing trials with oral paliperidone, the highest estimated ingestion was 405 mg.
Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, and QT prolongation. Torsades de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose with oral paliperidone.
Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert.
10.2Management of Overdosage Contact a Certified Poison Control Center for the most up to date information on the management of INVEGA SUSTENNA overdosage (1-800-222-1222 or www.poison.org). Provide supportive care, including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug.
Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs.
Use supportive and symptomatic measures. There is no specific antidote to paliperidone. Consider the prolonged-release characteristics of INVEGA SUSTENNA and the long apparent half-life of paliperidone when assessing treatment needs and recovery.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Paliperidone palmitate is hydrolyzed to paliperidone [see Clinical Pharmacology (12.3) ] . Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone is unclear. However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptor antagonism.
12.2Pharmacodynamics In vitro , paliperidone acts as an antagonist at the central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptors with binding affinities (Ki values) of 1.6–2.8 nM for D 2 and 0.8–1.2 nM for 5HT 2A receptors. Paliperidone is also active as an antagonist at histamine H 1 and α 1 and α 2 adrenergic receptors with binding affinities of 32 nM, 4 nM, 17 nM, respectively. Paliperidone has no affinity for cholinergic muscarinic or β 1 - and β 2 -adrenergic receptors.
The pharmacological activity of the (+)- and (-)- paliperidone enantiomers is qualitatively and quantitatively similar .
12.3Pharmacokinetics Absorption and Distribution Due to its extremely low water solubility, the 1-month formulation of paliperidone palmitate dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. Following a single intramuscular dose, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median T max of 13 days. The release of the drug starts as early as day 1 and lasts for as long as 126 days.
Following intramuscular injection of single doses (39 mg – 234 mg) in the deltoid muscle, on average, a 28% higher C max was observed compared with injection in the gluteal muscle. The two initial deltoid intramuscular injections of 234 mg on day 1 and 156 mg on day 8 help attain therapeutic concentrations rapidly. The release profile and dosing regimen of INVEGA SUSTENNA results in sustained therapeutic concentrations.
The AUC of paliperidone following INVEGA SUSTENNA administration was dose-proportional over a 39 mg-234 mg dose range, and less than dose-proportional for C max for doses exceeding 78 mg. The mean steady-state peak: trough ratio for an INVEGA SUSTENNA dose of 156 mg was 1.8 following gluteal administration and 2.2 following deltoid administration. Following administration of paliperidone palmitate the (+) and (-) enantiomers of paliperidone interconvert, reaching an AUC (+) to (-) ratio of approximately 1.6–1.8.
Based on a population analysis, the apparent volume of distribution of paliperidone is 391 L. The plasma protein binding of racemic paliperidone is 74%. Metabolism and Elimination In a study with oral immediate-release 14 C-paliperidone, one week following administration of a single oral dose of 1 mg immediate-release 14 C-paliperidone, 59% of the dose was excreted unchanged into urine, indicating that paliperidone is not extensively metabolized in the liver.
Approximately 80% of the administered radioactivity was recovered in urine and 11% in the feces. Four metabolic pathways have been identified in vivo , none of which accounted for more than 10% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, there is no evidence in vivo that these isozymes play a significant role in the metabolism of paliperidone.
Population pharmacokinetics analyses indicated no discernible difference on the apparent clearance of paliperidone after administration of oral paliperidone between extensive metabolizers and poor metabolizers of CYP2D6 substrates. The median apparent half-life of paliperidone following INVEGA SUSTENNA single-dose administration over the dose range of 39 mg – 234 mg ranged from 25 days – 49 days. Long-Acting Paliperidone Palmitate Injection versus Oral Extended-Release Paliperidone INVEGA SUSTENNA is designed to deliver pa… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Paliperidone palmitate is hydrolyzed to paliperidone [see Clinical Pharmacology (12.3) ] . Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone is unclear. However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptor antagonism.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING INVEGA SUSTENNA ® is available as a white to off-white sterile aqueous extended-release suspension for intramuscular injection in dose strengths of 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/mL, and 234 mg/1.5 mL paliperidone palmitate in single-dose prefilled syringes. The single-use kit contains a prefilled syringe and 2 safety needles (a 1 ½-inch 22 gauge safety needle and a 1-inch 23 gauge safety needle). 39 mg paliperidone palmitate kit (NDC 50458-560-01) 78 mg paliperidone palmitate kit (NDC 50458-561-01) 117 mg paliperidone palmitate kit (NDC 50458-562-01) 156 mg paliperidone palmitate kit (NDC 50458-563-01) 234 mg paliperidone palmitate kit (NDC 50458-564-01) Storage and Handling Store at room temperature (25 °C, 77 °F); excursions between 15 °C and 30 °C (between 59 °F and 86 °F) are permitted.
Do not mix with any other product or diluent.
📦 Storage and Handling ▾
Storage and Handling Store at room temperature (25 °C, 77 °F); excursions between 15 °C and 30 °C (between 59 °F and 86 °F) are permitted. Do not mix with any other product or diluent.
📋 Description ▾
11 DESCRIPTION INVEGA SUSTENNA ® contains paliperidone palmitate. The active ingredient, paliperidone, is an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. INVEGA SUSTENNA contains a racemic mixture of (+)- and (-)- paliperidone palmitate.
The chemical name is (9 RS )-3-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-4-oxo-6,7,8,9-tetrahydro-4 H -pyrido[1,2- a ]pyrimadin-9-yl hexadecanoate. Its molecular formula is C 39 H 57 FN 4 O 4 and its molecular weight is 664.89. The structural formula is: Paliperidone palmitate is very slightly soluble in ethanol and methanol, practically insoluble in polyethylene glycol 400 and propylene glycol, and slightly soluble in ethyl acetate.
INVEGA SUSTENNA is available as a white to off-white sterile aqueous extended-release suspension for intramuscular injection in the following dose strengths of paliperidone palmitate (and deliverable volumes) of the single-dose prefilled syringes: 39 mg (0.25 mL), 78 mg (0.5 mL), 117 mg (0.75 mL), 156 mg (1.0 mL), and 234 mg (1.5 mL). The drug product hydrolyzes to the active moiety, paliperidone, resulting in dose strengths of 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg of paliperidone, respectively. The inactive ingredients are polysorbate 20 (12 mg/mL), polyethylene glycol 4000 (30 mg/mL), citric acid monohydrate (5 mg/mL), disodium hydrogen phosphate anhydrous (5 mg/mL), sodium dihydrogen phosphate monohydrate (2.5 mg/mL), sodium hydroxide (2.84 mg/mL used as an alkalizing agent to set pH at 7), and water for injection.
INVEGA SUSTENNA is provided in a single-dose prefilled syringe (cyclic-olefin-copolymer) with a plunger stopper and tip cap (bromobutyl rubber). The kit also contains 2 safety needles (a 1 ½-inch 22 gauge safety needle and a 1-inch 23 gauge safety needle). Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient 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 their healthcare provider or report to the emergency room if they experience signs and symptoms of NMS, including hyperpyrexia, muscle rigidity, altered mental status including delirium, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions (5.3) ].
Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions (5.5) ]. 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 (5.6) ]. Orthostatic Hypotension Educate patients about the risk of orthostatic hypotension and syncope, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose [see Warnings and Precautions (5.7) ] .
Leukopenia/Neutropenia Advise patients with a pre-existing low WBC or a history of drug-induced leukopenia/neutropenia that they should have their CBC monitored while taking INVEGA SUSTENNA [see Warnings and Precautions (5.9) ] . Hyperprolactinemia Counsel patients on signs and symptoms of hyperprolactinemia that may be associated with chronic use of INVEGA SUSTENNA. 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 (5.10) ] .
Interference with Cognitive and Motor Performance Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that INVEGA SUSTENNA therapy does not affect them adversely [see Warnings and Precautions (5.11) ] . 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 (5.14) ] .
Heat Exposure and Dehydration Counsel patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions (5.15) ] . Concomitant Medication Advise patients to inform their healthcare providers if they are taking, or plan to take any prescription or over-the-counter medications because there is a potential for clinically significant interactions [see Drug Interactions (7) ] . Alcohol Advise patients to avoid alcohol during treatment with INVEGA SUSTENNA [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 INVEGA SUSTENNA. Advise patients that INVEGA SUSTENNA may cause extrapyramidal and/or withdrawal symptoms in a neonate. Advise patients that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to INVEGA SUSTENNA during pregnancy [see Use in Specific Populations (8.1) ] .
Lactation Advise breastfeeding women using INVEGA SUSTENNA to monitor infants for somnolence, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) and to seek medical care if they notice these signs [see Use in Specific Populations (8.2) ] . Infertility Advise females of reproductive potential that INVEGA SUSTENNA may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible [see Use… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption and Distribution Due to its extremely low water solubility, the 1-month formulation of paliperidone palmitate dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. Following a single intramuscular dose, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median T max of 13 days. The release of the drug starts as early as day 1 and lasts for as long as 126 days.
Following intramuscular injection of single doses (39 mg – 234 mg) in the deltoid muscle, on average, a 28% higher C max was observed compared with injection in the gluteal muscle. The two initial deltoid intramuscular injections of 234 mg on day 1 and 156 mg on day 8 help attain therapeutic concentrations rapidly. The release profile and dosing regimen of INVEGA SUSTENNA results in sustained therapeutic concentrations.
The AUC of paliperidone following INVEGA SUSTENNA administration was dose-proportional over a 39 mg-234 mg dose range, and less than dose-proportional for C max for doses exceeding 78 mg. The mean steady-state peak: trough ratio for an INVEGA SUSTENNA dose of 156 mg was 1.8 following gluteal administration and 2.2 following deltoid administration. Following administration of paliperidone palmitate the (+) and (-) enantiomers of paliperidone interconvert, reaching an AUC (+) to (-) ratio of approximately 1.6–1.8.
Based on a population analysis, the apparent volume of distribution of paliperidone is 391 L. The plasma protein binding of racemic paliperidone is 74%. Metabolism and Elimination In a study with oral immediate-release 14 C-paliperidone, one week following administration of a single oral dose of 1 mg immediate-release 14 C-paliperidone, 59% of the dose was excreted unchanged into urine, indicating that paliperidone is not extensively metabolized in the liver.
Approximately 80% of the administered radioactivity was recovered in urine and 11% in the feces. Four metabolic pathways have been identified in vivo , none of which accounted for more than 10% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, there is no evidence in vivo that these isozymes play a significant role in the metabolism of paliperidone.
Population pharmacokinetics analyses indicated no discernible difference on the apparent clearance of paliperidone after administration of oral paliperidone between extensive metabolizers and poor metabolizers of CYP2D6 substrates. The median apparent half-life of paliperidone following INVEGA SUSTENNA single-dose administration over the dose range of 39 mg – 234 mg ranged from 25 days – 49 days. Long-Acting Paliperidone Palmitate Injection versus Oral Extended-Release Paliperidone INVEGA SUSTENNA is designed to deliver paliperidone over a monthly period while extended-release oral paliperidone is administered on a daily basis.
The initiation regimen for INVEGA SUSTENNA (234 mg/156 mg in the deltoid muscle on Day 1/Day 8) was designed to rapidly attain steady-state paliperidone concentrations when initiating therapy without the use of oral supplementation. In general, overall initiation plasma levels with INVEGA SUSTENNA were within the exposure range observed with 6–12 mg extended-release oral paliperidone. The use of the INVEGA SUSTENNA initiation regimen allowed patients to stay in this exposure window of 6–12 mg extended-release oral paliperidone even on trough pre-dose days (Day 8 and Day 36).
The intersubject variability for paliperidone pharmacokinetics following delivery from INVEGA SUSTENNA was lower relative to the variability determined from extended-release oral paliperidone tablets. Because of the difference in median pharmacokinetic profiles between the two products, caution should be exercised when making a direct comparison of their pharmac… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics In vitro , paliperidone acts as an antagonist at the central dopamine Type 2 (D 2 ) and serotonin Type 2 (5HT 2A ) receptors with binding affinities (Ki values) of 1.6–2.8 nM for D 2 and 0.8–1.2 nM for 5HT 2A receptors. Paliperidone is also active as an antagonist at histamine H 1 and α 1 and α 2 adrenergic receptors with binding affinities of 32 nM, 4 nM, 17 nM, respectively. Paliperidone has no affinity for cholinergic muscarinic or β 1 - and β 2 -adrenergic receptors.
The pharmacological activity of the (+)- and (-)- paliperidone enantiomers is qualitatively and quantitatively similar .
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Schizophrenia Short-Term Monotherapy (Studies 1, 2, 3, 4) The efficacy of INVEGA SUSTENNA in the acute treatment of schizophrenia was evaluated in four short-term (one 9-week and three 13-week) double-blind, randomized, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. The fixed doses of INVEGA SUSTENNA in these studies were given on days 1, 8, and 36 in the 9-week study, and additionally on day 64 of the 13-week studies, i.e., at a weekly interval for the initial two doses and then every 4 weeks for maintenance.
Efficacy was evaluated using the total score on the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item scale that measures positive symptoms of schizophrenia (7 items), negative symptoms of schizophrenia (7 items), and general psychopathology (16 items), each rated on a scale of 1 (absent) to 7 (extreme); total PANSS scores range from 30 to 210. In Study 1 (PSY-3007), a 13-week study (n=636) comparing three fixed doses of INVEGA SUSTENNA (initial deltoid injection of 234 mg followed by 3 gluteal or deltoid doses of either 39 mg/4 weeks, 156 mg/4 weeks or 234 mg/4 weeks) to placebo, all three doses of INVEGA SUSTENNA were superior to placebo in improving the PANSS total score.
In Study 2 (PSY-3003), another 13-week study (n=349) comparing three fixed doses of INVEGA SUSTENNA (78 mg/4 weeks, 156 mg/4 weeks, and 234 mg/4 weeks) to placebo, only 156 mg/4 weeks of INVEGA SUSTENNA was superior to placebo in improving the PANSS total score. In Study 3 (PSY-3004), a third 13-week study (n=513) comparing three fixed doses of INVEGA SUSTENNA (39 mg/4 weeks, 78 mg/4 weeks, and 156 mg/4 weeks) to placebo, all three doses of INVEGA SUSTENNA were superior to placebo in improving the PANSS total score.
In Study 4 (SCH-201), the 9-week study (n=197) comparing two fixed doses of INVEGA SUSTENNA (78 mg/4 weeks and 156 mg/4 weeks) to placebo, both doses of INVEGA SUSTENNA were superior to placebo in improving PANSS total score. A summary of the mean baseline PANSS scores along with the mean changes from baseline in the four short-term acute schizophrenia studies are provided in Table 14. Table 14: Schizophrenia Short-term Studies Study Number Treatment Group Primary Efficacy Measure: PANSS Total Score Mean Baseline Score (SD) LS Mean Change from Baseline (SE) Placebo-subtracted Difference Difference (drug minus placebo) in least-squares mean change from baseline.
(95% CI) SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval. Study 1 INVEGA SUSTENNA (39 mg/4 weeks) p<0.05 (Doses statistically significantly superior to placebo). 86.9 (11.99) -11.2 (1.69) -5.1 (-9.01, -1.10) INVEGA SUSTENNA (156 mg/4 weeks) 86.2 (10.77) -14.8 (1.68) -8.7 (-12.62, -4.78) INVEGA SUSTENNA (234 mg/4 weeks) 88.4 (11.70) -15.9 (1.70) -9.8 (-13.71, -5.85) Placebo 86.8 (10.31) -6.1 (1.69) -- Study 2 Because an insufficient number of subjects received the 234 mg/4 weeks dose, results from this group are not included.
INVEGA SUSTENNA (78 mg/4 weeks) 89.9 (10.78) -6.9 (2.50) -3.5 (-8.73, 1.77) INVEGA SUSTENNA (156 mg/4 weeks) 90.1 (11.66) -10.4 (2.47) -6.9 (-12.12, -1.68) Placebo 92.4 (12.55) -3.5 (2.15) -- Study 3 INVEGA SUSTENNA (39 mg/4 weeks) 90.7 (12.25) -19.8 (2.19) -6.6 (-11.40, -1.73) INVEGA SUSTENNA (78 mg/4 weeks) 91.2 (12.02) -19.2 (2.19) -5.9 (-10.76, -1.07) INVEGA SUSTENNA (156 mg/4 weeks) 90.8 (11.70) -22.5 (2.18) -9.2 (-14.07, -4.43) Placebo 90.7 (12.22) -13.3 (2.21) -- Study 4 INVEGA SUSTENNA (78 mg/4 weeks) 88.0 (12.39) -4.6 (2.43) -11.2 (-16.85, -5.57) INVEGA SUSTENNA (156 mg/4 weeks) 85.2 (11.09) -7.4 (2.45) -14.0 (-19.51, -8.58) Placebo 87.8 (13.90) 6.6 (2.45) -- Maintenance Monotherapy Treatment (Study 5: PSY-3001) The efficacy of INVEGA SUSTENNA in maintaining symptomatic control in schizophrenia was established in a longer-term double-blind, placebo-controlled, flexible-dose study… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance INVEGA SUSTENNA (paliperidone) is not a controlled substance.
9.2Abuse Paliperidone has not been systematically studied in animals or humans for its potential for abuse.
9.3Dependence Paliperidone has not been systematically studied in animals or humans for its potential for tolerance or physical dependence.
🔒 Controlled Substance ▾
9.1Controlled Substance INVEGA SUSTENNA (paliperidone) is not a controlled substance.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis The carcinogenic potential of intramuscularly injected paliperidone palmitate was assessed in rats. There was an increase in mammary gland adenocarcinomas in female rats at 16, 47, and 94 mg/kg/month, which is 0.6, 2, and 4 times, respectively, the MRHD of 234 mg of INVEGA SUSTENNA based on mg/m 2 body surface area. A no-effect dose was not established.
Male rats showed an increase in mammary gland adenomas, fibroadenomas, and carcinomas at 2 and 4 times the MRHD based on mg/m 2 body surface area. A carcinogenicity study in mice has not been conducted with paliperidone palmitate. Carcinogenicity studies with risperidone, which is extensively converted to paliperidone in rats, mice, and humans, were conducted in Swiss albino mice and Wistar rats.
Risperidone was administered in the diet at daily doses of 0.63, 2.5, and 10 mg/kg for 18 months to mice and for 25 months to rats. A maximum tolerated dose was not achieved in male mice. There were statistically significant increases in pituitary gland adenomas, endocrine pancreas adenomas, and mammary gland adenocarcinomas.
The no-effect dose for these tumors was less than or equal to the maximum recommended human dose of risperidone based on mg/m 2 body surface area (see risperidone package insert). An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be mediated by prolonged dopamine D 2 antagonism and hyperprolactinemia. The relevance of these tumor findings in rodents to human risk is unclear [see Warnings and Precautions (5.7) ] .
Mutagenesis Paliperidone palmitate showed no genotoxicity in the in vitro Ames bacterial reverse mutation test or the mouse lymphoma assay. Paliperidone was not genotoxic in the in vitro Ames bacterial reverse mutation test, the mouse lymphoma assay, or the in vivo rat bone marrow micronucleus test. Impairment of Fertility No fertility studies were conducted with paliperidone palmitate.
In an oral paliperidone study of fertility, the percentage of treated female rats that became pregnant was not affected at oral doses of paliperidone of up to 2.5 mg/kg/day which is 2 times the MRHD based on mg/m 2 body surface area. However, pre- and post-implantation loss was increased, and the number of live embryos was slightly decreased, at 2.5 mg/kg, a dose that also caused slight maternal toxicity. These parameters were not affected at a dose of 0.63 mg/kg, which is half of the MRHD based on mg/m 2 body surface area.
The fertility of male rats was not affected at oral doses of paliperidone of up to 2 times the MRHD of 12 mg/day based on mg/m 2 body surface area, although sperm count and sperm viability studies were not conducted with paliperidone. In a subchronic study in Beagle dogs with risperidone, which is extensively converted to paliperidone in dogs and humans, all doses tested (0.31 mg/kg – 5.0 mg/kg) resulted in decreases in serum testosterone and in sperm motility and concentration (0.6 to 10 times the MRHD of 16 mg/day for risperidone, based on mg/m 2 body surface area).
Serum testosterone and sperm parameters partially recovered, but remained decreased after the last observation (two months after treatment was discontinued).
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis The carcinogenic potential of intramuscularly injected paliperidone palmitate was assessed in rats. There was an increase in mammary gland adenocarcinomas in female rats at 16, 47, and 94 mg/kg/month, which is 0.6, 2, and 4 times, respectively, the MRHD of 234 mg of INVEGA SUSTENNA based on mg/m 2 body surface area. A no-effect dose was not established.
Male rats showed an increase in mammary gland adenomas, fibroadenomas, and carcinomas at 2 and 4 times the MRHD based on mg/m 2 body surface area. A carcinogenicity study in mice has not been conducted with paliperidone palmitate. Carcinogenicity studies with risperidone, which is extensively converted to paliperidone in rats, mice, and humans, were conducted in Swiss albino mice and Wistar rats.
Risperidone was administered in the diet at daily doses of 0.63, 2.5, and 10 mg/kg for 18 months to mice and for 25 months to rats. A maximum tolerated dose was not achieved in male mice. There were statistically significant increases in pituitary gland adenomas, endocrine pancreas adenomas, and mammary gland adenocarcinomas.
The no-effect dose for these tumors was less than or equal to the maximum recommended human dose of risperidone based on mg/m 2 body surface area (see risperidone package insert). An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be mediated by prolonged dopamine D 2 antagonism and hyperprolactinemia. The relevance of these tumor findings in rodents to human risk is unclear [see Warnings and Precautions (5.7) ] .
Mutagenesis Paliperidone palmitate showed no genotoxicity in the in vitro Ames bacterial reverse mutation test or the mouse lymphoma assay. Paliperidone was not genotoxic in the in vitro Ames bacterial reverse mutation test, the mouse lymphoma assay, or the in vivo rat bone marrow micronucleus test. Impairment of Fertility No fertility studies were conducted with paliperidone palmitate.
In an oral paliperidone study of fertility, the percentage of treated female rats that became pregnant was not affected at oral doses of paliperidone of up to 2.5 mg/kg/day which is 2 times the MRHD based on mg/m 2 body surface area. However, pre- and post-implantation loss was increased, and the number of live embryos was slightly decreased, at 2.5 mg/kg, a dose that also caused slight maternal toxicity. These parameters were not affected at a dose of 0.63 mg/kg, which is half of the MRHD based on mg/m 2 body surface area.
The fertility of male rats was not affected at oral doses of paliperidone of up to 2 times the MRHD of 12 mg/day based on mg/m 2 body surface area, although sperm count and sperm viability studies were not conducted with paliperidone. In a subchronic study in Beagle dogs with risperidone, which is extensively converted to paliperidone in dogs and humans, all doses tested (0.31 mg/kg – 5.0 mg/kg) resulted in decreases in serum testosterone and in sperm motility and concentration (0.6 to 10 times the MRHD of 16 mg/day for risperidone, based on mg/m 2 body surface area).
Serum testosterone and sperm parameters partially recovered, but remained decreased after the last observation (two months after treatment was discontinued).
📄 Patient Package Insert ▾
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: January 2025 PATIENT INFORMATION INVEGA SUSTENNA ® (in-VAY-guh suss-TEN-uh) (paliperidone palmitate) Extended-Release Injectable Suspension What is the most important information I should know about INVEGA SUSTENNA?
INVEGA SUSTENNA can cause serious side effects, including: Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis). INVEGA SUSTENNA is not for treating dementia-related psychosis. What is INVEGA SUSTENNA?
INVEGA SUSTENNA is a prescription medicine given by injection by a healthcare professional and used to treat: schizophrenia in adults schizoaffective disorder in adults either alone or with other medicines such as mood stabilizers or antidepressants It is not known if INVEGA SUSTENNA is safe and effective in children under 18 years of age. Who should not receive INVEGA SUSTENNA? Do not receive INVEGA SUSTENNA if you: are allergic to paliperidone, paliperidone palmitate, risperidone, or any of the ingredients in INVEGA SUSTENNA.
See the end of this Patient Information leaflet for a complete list of ingredients in INVEGA SUSTENNA. What should I tell my healthcare provider before receiving INVEGA SUSTENNA? Before you receive INVEGA SUSTENNA, tell your healthcare provider about all your medical conditions, including if you: have had Neuroleptic Malignant Syndrome (NMS) have or have had heart problems, including a heart attack, heart failure, abnormal heart rhythm, or long QT syndrome have or have had low levels of potassium or magnesium in your blood have or have had uncontrolled movements of your tongue, face, mouth, or jaw (tardive dyskinesia) have or have had kidney or liver problems have diabetes or have a family history of diabetes have had a low white blood cell count have had problems with dizziness or fainting or are being treated for high blood pressure have or have had seizures or epilepsy have any other medical conditions are pregnant or plan to become pregnant.
It is not known if INVEGA SUSTENNA will harm your unborn baby. If you become pregnant while taking INVEGA SUSTENNA, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. You can register by calling 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/.
Infants born to women who are treated with INVEGA SUSTENNA may experience symptoms such as tremors, irritability, excessive sleepiness, eye twitching, muscle spasms, decreased appetite, difficulty breathing, or abnormal movement of arms and legs. Let your healthcare provider know if these symptoms occur. are breastfeeding or plan to breastfeed. INVEGA SUSTENNA can pass into your breast milk.
Talk to your healthcare provider about the best way to feed your baby if you receive INVEGA SUSTENNA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take.
Keep a list of them to show to your healthcare provider or pharmacist when you get a new medicine. How will I receive INVEGA SUSTENNA? Follow your INVEGA SUSTENNA treatment schedule exactly as your healthcare provider tells you to.
Your healthcare provider will tell you how much INVEGA SUSTENNA you will receive and when you will receive it. INVEGA SUSTENNA is given as an injection by your healthcare provider into the muscle (intramuscularly) of your arm or your buttocks. When you receive your first dose of INVEGA SUSTENNA you will need to get a second dose 1 week later.
After that you will only need to get a dose 1 time a month. What should I avoid while receiving INVEGA SUSTENNA? INVEGA SUSTENNA may affect your ability to make decisions, think clearly, or react quickly.
Do not drive, operate heavy machinery, or do other dangerous activities until you… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
INSTRUCTIONS FOR USE INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension Rx only Single use only PLEASE READ COMPLETE INSTRUCTIONS PRIOR TO USE For deltoid and gluteal intramuscular injection only Please see accompanying full Package Insert. IMPORTANT RESOURCES For additional information, visit www.invegasustenna.com or call Janssen Pharmaceuticals, Inc. at 1-800-526-7736. Kit contents Each injection must be administered only by a health care professional.
The kit contains a prefilled syringe and 2 safety needles (a 1 ½-inch 22 gauge needle and a 1-inch 23 gauge needle) for intramuscular injection. INVEGA SUSTENNA is for single use only. INVEGA SUSTENNA is intended for intramuscular use only.
Inject slowly, deep into the muscle. Care should be taken to avoid inadvertent injection into a blood vessel. Each injection should be administered by a health care professional.
Administration should be in a single injection. Do not administer the dose in divided injections. Do not administer intravascularly or subcutaneously.
INSTRUCTIONS FOR USE Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous suspension. Select the appropriate needle. For DELTOID injection: If the patient weighs less than 90 kg, use the 1-inch 23 gauge needle (needle with blue colored hub).
If the patient weighs 90 kg or more, use the 1 ½-inch 22 gauge needle (needle with gray colored hub). For GLUTEAL injection: Use the 1 ½-inch 22 gauge needle (needle with gray colored hub) regardless of patient's weight. Hold the syringe with the tip cap pointing up.
Remove the rubber tip cap with a gentle twisting motion. Peel the safety needle pouch half way open. Grasp the needle sheath using the plastic peel pouch.
Hold the syringe pointing up. Attach the safety needle to the syringe using a gentle twisting motion to avoid needle hub cracks or damage. Always check for signs of damage or leaking prior to administration.
Pull the needle sheath away from the needle with a straight pull. Do not twist the sheath as the needle may be loosened from the syringe. Bring the syringe with the attached needle in upright position to de-aerate.
De-aerate the syringe by moving the plunger rod carefully forward. Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal muscle of the patient. Do not administer by any other route.
After the injection is complete, use either thumb or finger of one hand (h1, h2) or a flat surface (h3) to activate the needle protection system. The needle protection system is fully activated when a 'click' is heard. Discard the syringe with needle appropriately.
Keep out of reach of children. h1 h2 h3 Manufactured for: Janssen Pharmaceuticals, Inc. Titusville, NJ 08560, USA For patent information: www.janssenpatents.com © Johnson & Johnson and its affiliates 2009 This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 2/2025 Image Image Image Image Image Image Image Image Image
📄 Recent Major Changes ▾
Dosage and Administration ( 2.7 ) 9/2024 Warnings and Precautions ( 5.10 ) 1/2025
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 39 mg Syringe Kit NDC 50458-560-01 Rx only Single-dose prefilled syringe. Use entire contents of syringe. INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension 39 mg/0.25 mL 39 mg/0.25 mL Each single-dose prefilled syringe contains 39 mg (0.25 mL) paliperidone palmitate.
FOR INTRAMUSCULAR INJECTION ONLY Shake before using Each injection must be administered only by a healthcare professional. CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1½-inch safety needle and a 23G, 1-inch safety needle) Store at room temperature (77°F, 25°C); excursions between 59°F and 86°F (15°C and 30°C) are permitted. For initiation and monthly maintenance dosing instructions, please see accompanying full Package Insert. janssen PRINCIPAL DISPLAY PANEL - 39 mg Syringe Kit
PRINCIPAL DISPLAY PANEL - 78 mg Syringe Kit NDC 50458-561-01 Rx only Single-dose prefilled syringe. Use entire contents of syringe. INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension 78 mg/0.5 mL 78 mg/0.5 mL Each single-dose prefilled syringe contains 78 mg (0.5 mL) paliperidone palmitate.
FOR INTRAMUSCULAR INJECTION ONLY Shake before using Each injection must be administered only by a healthcare professional. CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1½-inch safety needle and a 23G, 1-inch safety needle) Store at room temperature (77°F, 25°C); excursions between 59°F and 86°F (15°C and 30°C) are permitted. For initiation and monthly maintenance dosing instructions, please see accompanying full Package Insert. janssen PRINCIPAL DISPLAY PANEL - 78 mg Syringe Kit
PRINCIPAL DISPLAY PANEL - 117 mg Syringe Kit NDC 50458-562-01 Rx only Single-dose prefilled syringe. Use entire contents of syringe. INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension 117 mg/0.75 mL 117 mg/0.75 mL Each single-dose prefilled syringe contains 117 mg (0.75 mL) paliperidone palmitate.
FOR INTRAMUSCULAR INJECTION ONLY Shake before using Each injection must be administered only by a healthcare professional. CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1½-inch safety needle and a 23G, 1-inch safety needle) Store at room temperature (77°F, 25°C); excursions between 59°F and 86°F (15°C and 30°C) are permitted. For initiation and monthly maintenance dosing instructions, please see accompanying full Package Insert. janssen PRINCIPAL DISPLAY PANEL - 117 mg Syringe Kit
PRINCIPAL DISPLAY PANEL - 156 mg Syringe Kit NDC 50458-563-01 Rx only Single-dose prefilled syringe. Use entire contents of syringe. INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension 156 mg/mL 156 mg/mL Each single-dose prefilled syringe contains 156 mg (1 mL) paliperidone palmitate.
FOR INTRAMUSCULAR INJECTION ONLY Shake before using Each injection must be administered only by a healthcare professional. CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1½-inch safety needle and a 23G, 1-inch safety needle) Store at room temperature (77°F, 25°C); excursions between 59°F and 86°F (15°C and 30°C) are permitted. For initiation and monthly maintenance dosing instructions, please see accompanying full Package Insert. janssen PRINCIPAL DISPLAY PANEL - 156 mg Syringe Kit
PRINCIPAL DISPLAY PANEL - 234 mg Syringe Kit NDC 50458-564-01 Rx only Single-dose prefilled syringe. Use entire contents of syringe. INVEGA SUSTENNA ® (paliperidone palmitate) extended-release injectable suspension 234 mg/1.5 mL 234 mg/1.5 mL Each single-dose prefilled syringe contains 234 mg (1.5 mL) paliperidone palmitate.
FOR INTRAMUSCULAR INJECTION ONLY Shake before using Each injection must be administered only by a healthcare professional. CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1½-inch safety needle and a 23G, 1-inch safety needle) Store at room temperature (77°F, 25°C); excursions between 59°F and 86°F (15°C and 30°C) are permitted. For initiatio… [Excerpted — this section continues on DailyMed.]
Medicaid utilization & spend
Medicaid utilization by pack size
Medicare Part D spend CMS · PART D · 2026 (Q1)
About this NDC listing & data coverage
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) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |