INVEGA TRINZA paliperidone palmitate 819 mg/2.63mL Injection, Suspension, Extended Release, 1 syringe — NDC 50458-609-01 (Billing 50458-0609-01)
This is a package of 1 syringe of INVEGA TRINZA paliperidone palmitate 819 mg/2.63mL Injection, Suspension, Extended Release from Janssen Pharmaceuticals, Inc, marketed since May 2015 and currently FDA-listed; retail pharmacies pay about $3,997.97 per mL (NADAC). It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 50458-609-01 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 50458 labeler · 609 product · 01 package
- Package marketed since
- May 19, 2015
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2026
- Barcode (UPC-A, from the NDC)
- 3 5045860901 1
- Medicaid fills, this package
- 32,192 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): 074143
- GCN: 38702
- GPI-14 (Medi-Span): 5907005010E655
- HICL (First Databank): 036479
- AHFS class code: 28:16.08.04
- RxCUI (RxNorm): 1650966
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 8, 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 8, 2026
Clinical
Paliperidone extended-release injections are used to treat schizophrenia (a mental illness that affects how a person thinks, feels and behaves) and schizoaffective disorder (a mental illness that causes both a loss of contact with reality and mood problems such as depression or mania). Paliperidone extended-release injection 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 ↗- 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 | $3,997.970 | $3,997.97 / 1 ml |
| Medicaid paysCMS SDUD · 12 mo | $3,863.36 | $3,863.36 / 1 ml |
| Medicare drug plans payPart D · Q2 2026 | $4,044.26 | $4,044.26 / 1 ml |
| Medicare Part B allowsASP · J2427 | $13.262 / J2427 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 | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 50458-0609-01 You're viewing this Main listing | 1 SYRINGE in 1 KIT / 1 mL in 1 SYRINGE | 2015-05-19 | — | Active |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Invega Trinza 819 mg/2.63mLthis 50458-0609-01 | Janssen | 1 syringe | $3,997.970 | — | Availability likely | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Orange Book · refreshed Oct 9, 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.
Our estimate: April 2036 about 9.5 years away
How sure: Very likely. Few things could still move it, but a court ruling or a new deal can.
Why then: A patent that protects the brand runs out. After that, approved generics can be sold.
That is before the November 2041 date above, which is common: a court ruling or a deal with the brand’s maker often lets a generic in before the last patent runs out.
See the full forecast for generic Invega Trinza →🛈 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 10143693 ↗ | Method of use | U-2457 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2458 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2458 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2457 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2458 | Apr 5, 2036 |
| US 11324751 ↗ | Method of use | U-3359 | May 7, 2041 |
| US 11324751 ↗ | Method of use | U-3359 | May 7, 2041 |
| US 11304951 ↗ | Method of use | U-3349 | May 7, 2041 |
| US 11304951 ↗ | Method of use | U-3349 | May 7, 2041 |
| US 12208100 ↗ | Method of use | U-3359 | May 7, 2041 |
| US 12208100 ↗ | Method of use | U-4110 | May 7, 2041 |
| US 12208100 ↗ | Method of use | U-4110 | May 7, 2041 |
| US 12208100 ↗ | Method of use | U-3359 | May 7, 2041 |
| US 10143693 ↗ | Method of use | U-2457 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2458 | Apr 5, 2036 |
| US 10143693 ↗ | Method of use | U-2457 | Apr 5, 2036 |
| US 11666697 ↗ | Method of use | U-3626 | Nov 24, 2041 |
| US 11666697 ↗ | Method of use | U-3626 | Nov 24, 2041 |
Is there a generic version of INVEGA TRINZA 819 MG/2.63 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 9, 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.
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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.
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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.
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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.
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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.
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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.
5 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
- CONCERTA Methylphenidate hydrochloride 54 mg Tablet, Extended Release NDC 50458-587-01
- CONCERTA Methylphenidate hydrochloride 27 mg Tablet, Extended Release NDC 50458-588-01
- Risperidone 1 mg/mL Solution NDC 50458-596-01
- INVEGA TRINZA paliperidone palmitate 273 mg/.88mL Injection, Suspension, Extended Release NDC 50458-606-01
- INVEGA TRINZA paliperidone palmitate 410 mg/1.32mL Injection, Suspension, Extended Release NDC 50458-607-01
- INVEGA TRINZA paliperidone palmitate 546 mg/1.75mL Injection, Suspension, Extended Release NDC 50458-608-01
- INVEGA HAFYERA paliperidone palmitate 1092 mg/3.5mL Injection, Suspension, Extended Release NDC 50458-611-01
- INVEGA HAFYERA paliperidone palmitate 1560 mg/5mL Injection, Suspension, Extended Release NDC 50458-612-01
- Topamax topiramate 25 mg Tablet, Coated NDC 50458-639-65
- Topamax topiramate 50 mg Tablet, Coated NDC 50458-640-65
- Topamax topiramate 100 mg Tablet, Coated NDC 50458-641-65
- Topamax topiramate 200 mg Tablet, Coated NDC 50458-642-65
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 TRINZA 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 TRINZA is not approved for use in patients with dementia-related psychosis. ( 5.1 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE INVEGA TRINZA (paliperidone palmitate), a 3-month injection, is indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA (1-month paliperidone palmitate extended-release injectable suspension) for at least four months [see Dosage and Administration (2.2) and Clinical Studies (14) ] . INVEGA TRINZA, a 3-month injection, is an atypical antipsychotic indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA (1-month paliperidone palmitate extended-release injectable suspension) for at least four months.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Use INVEGA TRINZA only after the patient has been adequately treated with the 1-month paliperidone palmitate extended-release injectable suspension for at least four months. ( 2.2 ) INVEGA TRINZA should be administered once every 3 months. ( 2.1 ) For intramuscular injection only.
( 2.1 ) Each injection must be administered only by a healthcare professional. ( 2.1 ) For deltoid injection: For patients weighing less than 90 kg, use the 1-inch 22 gauge thin wall needle. For patients weighing 90 kg or more, use the 1½-inch 22 gauge thin wall needle.
For gluteal injection: Regardless of patient weight, use the1½-inch 22 gauge thin wall needle. Prior to administration, shake the prefilled syringe vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension. ( 2.1 ) Initiate INVEGA TRINZA when the next 1-month paliperidone palmitate dose is scheduled with an INVEGA TRINZA dose based on the previous 1-month injection dose as shown below.
( 2.2 ) INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA If the Last Dose of INVEGA SUSTENNA is: Initiate INVEGA TRINZA at the Following Dose: 78 mg 273 mg 117 mg 410 mg 156 mg 546 mg 234 mg 819 mg Conversion from the INVEGA SUSTENNA 39 mg dose was not studied. Missed Doses: Missing doses of INVEGA TRINZA should be avoided. To manage missed doses on exceptional occasions, refer to the Full Prescribing Information.
( 2.3 ) Moderate to severe renal impairment (creatinine clearance < 50 mL/min): INVEGA TRINZA is not recommended. ( 2.5 ) Mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min): Adjust dosage and stabilize the patient using INVEGA SUSTENNA, then transition to INVEGA TRINZA. See above table .
( 2.5 )
2.1Administration Instructions INVEGA TRINZA should be administered once every 3 months. 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.
It is important to shake the syringe vigorously for at least 15 seconds to ensure a homogeneous suspension. Inject INVEGA TRINZA within 5 minutes of shaking vigorously [see Dosage and Administration (2.8) ] . INVEGA TRINZA 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 TRINZA must be administered using only the thin wall needles that are provided in the INVEGA TRINZA pack. Do not use needles from the 1-month paliperidone palmitate extended-release injectable suspension pack or other commercially-available needles to reduce the risk of blockage.
Deltoid Injection The recommended needle size for administration of INVEGA TRINZA into the deltoid muscle is determined by the patient's weight: For patients weighing less than 90 kg, the 1-inch, 22 gauge thin wall needle is recommended. For patients weighing 90 kg or more, the 1½-inch, 22 gauge thin wall needle is recommended. Administer into the center of the deltoid muscle.
Deltoid injections should be alternated between the two deltoid muscles. Gluteal Injection Regardless of patient weight, the recommended needle size for administration of INVEGA TRINZA into the gluteal muscle is the 1½-inch, 22 gauge thin wall needle. Administer into the upper-outer quadrant of the gluteal muscle.
Gluteal injections should be alternated between the two gluteal muscles. Incomplete Administration To avoid an incomplete administration of INVEGA TRINZA, ensure that the prefilled syringe is shaken vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension and ensure the needle does not get clogged during injection [see Dosage and Administration (2.8) ] . However, in the event of an incompletely… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS INVEGA TRINZA is available as a white to off-white aqueous extended-release injectable suspension for intramuscular injection in dose strengths of 273 mg/0.88 mL, 410 mg/1.32 mL, 546 mg/1.75 mL, and 819 mg/2.63 mL paliperidone palmitate in single-dose prefilled syringes. Extended-release injectable suspension: 273 mg/0.88 mL, 410 mg/1.32 mL, 546 mg/1.75 mL, or 819 mg/2.63 mL ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS INVEGA TRINZA is contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the INVEGA TRINZA 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 TRINZA. ( 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, including fatalities). INVEGA TRINZA is not approved for use in patients with dementia-related psychosis ( 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: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk.
These metabolic changes include: Hyperglycemia and Diabetes Mellitus: Monitor for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. ( 5.6 ) Dyslipidemia: Undesirable alterations have been observed.
( 5.6 ) Weight Gain: Significant weight gain has been reported. Monitor weight gain. ( 5.6 ) Orthostatic Hypotension and Syncope: Use with caution in patients with known cardiovascular or cerebrovascular disease and patients predisposed to hypotension ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis: Monitor complete blood count in patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia.
Consider discontinuation 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 TRINZA 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, the 1-month paliperidone palmitate extended-release injectable suspension, or INVEGA TRINZA in elderly patients with dementia.
These medications are not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and… [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 reaction, weight increased, headache, upper respiratory tract infection, akathisia, and parkinsonism.
( 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 include data from two clinical trials. One is a long-term maintenance trial, in which 506 subjects with schizophrenia received several doses of the 1-month paliperidone palmitate extended-release injectable suspension during the open-label phase, of which 379 subjects continued to receive a single injection of INVEGA TRINZA during the open-label phase, and 160 subjects were subsequently randomized to receive at least one dose of INVEGA TRINZA and 145 subjects received placebo during the double-blind placebo-controlled phase.
The mean (SD) duration of exposure during the double-blind phase was 150 (79) days in the placebo group and 175 (90) days in the INVEGA TRINZA group. The other is a Phase 1 study (N=308), which included patients with schizophrenia who received a single injection of INVEGA TRINZA concomitantly with other oral antipsychotics. Adverse Reactions in a Double-Blind, Placebo-Controlled (Long-Term Maintenance) Clinical Trial Commonly Observed Adverse Reactions: The most common adverse reactions (incidence at least 5% in the open-label phase, or in the INVEGA TRINZA group and at least twice the incidence in the placebo group during the double-blind phase) were injection site reaction, weight increased, headache, upper respiratory tract infection, akathisia, and parkinsonism.
Discontinuation of Treatment Due to Adverse Events: The percentages of subjects who discontinued due to adverse events in the long-term maintenance trial were 5.1% during the open-label phase. During the double-blind phase, no INVEGA TRINZA-treated subject and one placebo-treated subject discontinued due to adverse events. Adverse Reactions Occurring at an Incidence of 2% or More in INVEGA TRINZA - Treated Patients: The safety profile of INVEGA TRINZA was similar to that seen with the 1-month paliperidone extended-release injectable suspension.
Table 8 lists the adverse reactions reported in a long-term maintenance trial in subjects with schizophrenia. Table 8. Incidences of Adverse Reactions 2% or More of INVEGA TRINZA-Treated Patients (and Greater than Placebo) for the Open-Lab… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS 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 TRINZA. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended release tablets. ( 7.2 , 12.3 )
7.1Drugs Having Clinically Important Interactions with INVEGA TRINZA 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. In addition, consider the 3-month dosing interval and long half-life of INVEGA TRINZA [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) ] . Table 11.
Clinically Important Drug Interactions with INVEGA TRINZA 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 TRINZA. INVEGA TRINZA 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 TRINZA has the potential for inducing orthostatic hypotension, an additive effect may occur when INVEGA TRINZA 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 TRINZA during the 3-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 (2.7) ] . 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 TRINZA Based on pharmacokinetic studies with oral paliperidone, no dosage adjustment of INVEGA TRINZA is required when administered concomitantly with valproate [see Clinical Pharmacology (12.3) ]. Additionally, no dosage adjustment is necessary for valproate when co-administered with INVEGA TRINZA [see Clinical Pharmacology (12.3) ] . Pharmacokinetic interaction between lithium and INVEGA TRINZA is 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 TRINZA, 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 TRINZA during pregnancy (see Clinical Considerations ) . Paliperidone has been detected in plasma in adult subjects up to 18 months after a single-dose administration of INVEGA TRINZA [see Clinical Pharmacology (12.3) ] , and the clinical significance of INVEGA TRINZA 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 is 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 TRINZA, during the third trimester of pregnancy. These symptoms have varied in severity.
Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A prospective observational study including 6 women treated with risperidone, the parent compound of paliperidone, demonstrated placental passage of risperidone and paliperidone. A retrospective cohort study from a Medic… [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 TRINZA, 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 TRINZA during pregnancy (see Clinical Considerations ) . Paliperidone has been detected in plasma in adult subjects up to 18 months after a single-dose administration of INVEGA TRINZA [see Clinical Pharmacology (12.3) ] , and the clinical significance of INVEGA TRINZA 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 is 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 TRINZA, during the third trimester of pregnancy. These symptoms have varied in severity.
Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Published data from observational studies, birth registries, and case reports on the use of atypical antipsychotics during pregnancy do not report a clear association with antipsychotics and major birth defects.
A prospective observational study including 6 women treated with risperidone, 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 increased risk for major birth defects. There… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of INVEGA TRINZA in patients less than 18 years of age have not been established. Use of INVEGA TRINZA is not recommended in pediatric patients because of the potential longer duration of an adverse event compared to shorter-acting products. In clinical trials of oral paliperidone, there were notably higher incidences of dystonia, hyperkinesia, tremor, and parkinsonism in the adolescent population as compared to the adult studies.
Juvenile Animal Studies No juvenile animal studies were conducted with the 3-month paliperidone palmitate extended-release injectable suspension. 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 TRINZA on growth and sexual maturation have not been fully evaluated in children and adolescents.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of INVEGA TRINZA 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, monitor renal function and adjust dosage [see Dosage and Administration (2.5) ].
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Human Experience No cases of overdose were reported in premarketing studies with paliperidone palmitate injection. Because INVEGA TRINZA 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 paliperidone and INVEGA TRINZA 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 TRINZA 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 3-month formulation of paliperidone palmitate dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The release of the drug starts as early as day 1 and lasts for as long as 18 months. Following a single intramuscular dose of INVEGA TRINZA, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median T max of 30–33 days.
Following intramuscular injection of INVEGA TRINZA at doses of 273–819 mg in the deltoid muscle, on average, an 11–12% higher C max was observed compared with injection in the gluteal muscle. The release profile and dosing regimen of INVEGA TRINZA results in sustained therapeutic concentrations over 3 months. The total and peak exposure of paliperidone following INVEGA TRINZA administration was dose-proportional over a 273–819 mg dose range.
The mean steady-state peak:trough ratio for a INVEGA TRINZA dose was 1.6 following gluteal administration and 1.7 following deltoid administration. Following administration of INVEGA TRINZA, the apparent volume of distribution of paliperidone is 1960 L. The plasma protein binding of racemic paliperidone is 74%.
Following administration of INVEGA TRINZA, the (+) and (-) enantiomers of paliperidone interconvert, reaching an AUC (+) to (-) ratio of approximately 1.7–1.8. 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 TRINZA administration over the dose range of 273–819 mg ranged from 84–95 days following deltoid injections and 118–139 days following gluteal injections. The concentration of paliperidone remaining in the circulation 18 months after dosing of 819 mg INVEGA TRINZA is stopped is estimated to be 3% (following deltoid injection) or 7% (following gluteal injection) of the average steady-sta… [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 TRINZA ® is available as a white to off-white sterile aqueous extended-release suspension for intramuscular injection in dose strengths of 273 mg/0.88 mL, 410 mg/1.32 mL, 546 mg/1.75 mL, and 819 mg/2.63 mL paliperidone palmitate in single-dose prefilled syringes. The single-use kit contains a prefilled syringe and 2 safety needles (a thin walled 22G, 1-inch safety needle and a thin walled 22G, 1½-inch safety needle). 273 mg paliperidone palmitate kit (NDC 50458-606-01) 410 mg paliperidone palmitate kit (NDC 50458-607-01) 546 mg paliperidone palmitate kit (NDC 50458-608-01) 819 mg paliperidone palmitate kit (NDC 50458-609-01) Storage and Handling Store at room temperature 20°C to 25°C (68°F to 77°F); excursions between 15°C and 30°C (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 20°C to 25°C (68°F to 77°F); excursions between 15°C and 30°C (59°F and 86°F) are permitted. Do not mix with any other product or diluent.
📋 Description ▾
11 DESCRIPTION INVEGA TRINZA ® contains paliperidone palmitate. The active ingredient, paliperidone, is an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. INVEGA TRINZA 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 TRINZA is available as a white to off-white sterile aqueous extended-release suspension for intramuscular injection in dose strengths of 273 mg, 410 mg, 546 mg, and 819 mg paliperidone palmitate in single-dose prefilled syringes. The drug product hydrolyzes to the active moiety, paliperidone, resulting in dose strengths of 175 mg, 263 mg, 350 mg, and 525 mg of paliperidone, respectively. The inactive ingredients are polysorbate 20 (10 mg/mL), polyethylene glycol 4000 (75 mg/mL), citric acid monohydrate (7.5 mg/mL), sodium dihydrogen phosphate monohydrate (6 mg/mL), sodium hydroxide (5.4 mg/mL used as an alkalizing agent to set the pH at 7), and water for injection.
INVEGA TRINZA is provided in a single-dose prefilled syringe (cyclic-olefin-copolymer) with either 175 mg (0.875 mL), 263 mg (1.315 mL), 350 mg (1.75 mL), or 525 mg (2.625 mL) paliperidone (as 273 mg, 410 mg, 546 mg, or 819 mg paliperidone palmitate) suspension with a plunger stopper and tip cap (bromobutyl rubber), a backstop, and 2 types of commercially available needles: a thin walled 22G, 1 ½-inch safety needle and a thin walled 22G, 1-inch 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 TRINZA [see Warnings and Precautions (5.9) ] . Hyperprolactinemia Counsel patients on signs and symptoms of hyperprolactinemia that may be associated with chronic use of INVEGA TRINZA. 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 TRINZA 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 [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 TRINZA [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 TRINZA.
Advise patients that INVEGA TRINZA 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 TRINZA during pregnancy [see Use in Specific Populations (8.1) ] . Lactation Advise breastfeeding women using INVEGA TRINZA 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 TRINZA may impair fertility due to an increase in serum prolactin levels. The effects on fertility are reversible [see Use in Specific Population… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption and Distribution Due to its extremely low water solubility, the 3-month formulation of paliperidone palmitate dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The release of the drug starts as early as day 1 and lasts for as long as 18 months. Following a single intramuscular dose of INVEGA TRINZA, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median T max of 30–33 days.
Following intramuscular injection of INVEGA TRINZA at doses of 273–819 mg in the deltoid muscle, on average, an 11–12% higher C max was observed compared with injection in the gluteal muscle. The release profile and dosing regimen of INVEGA TRINZA results in sustained therapeutic concentrations over 3 months. The total and peak exposure of paliperidone following INVEGA TRINZA administration was dose-proportional over a 273–819 mg dose range.
The mean steady-state peak:trough ratio for a INVEGA TRINZA dose was 1.6 following gluteal administration and 1.7 following deltoid administration. Following administration of INVEGA TRINZA, the apparent volume of distribution of paliperidone is 1960 L. The plasma protein binding of racemic paliperidone is 74%.
Following administration of INVEGA TRINZA, the (+) and (-) enantiomers of paliperidone interconvert, reaching an AUC (+) to (-) ratio of approximately 1.7–1.8. 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 TRINZA administration over the dose range of 273–819 mg ranged from 84–95 days following deltoid injections and 118–139 days following gluteal injections. The concentration of paliperidone remaining in the circulation 18 months after dosing of 819 mg INVEGA TRINZA is stopped is estimated to be 3% (following deltoid injection) or 7% (following gluteal injection) of the average steady-state levels. Long-acting 3-month paliperidone palmitate injection versus other paliperidone formulations INVEGA TRINZA is designed to deliver paliperidone over a 3-month period, while 1-month paliperidone palmitate injection is administered on a monthly basis.
INVEGA TRINZA, when administered at doses that are 3.5-fold higher than the corresponding dose of 1-month paliperidone palmitate injection, results in paliperidone exposures similar to those obtained with corresponding monthly doses of 1-month paliperidone palmitate injection and corresponding once daily doses of paliperidone extended-release tablets. The exposure range for INVEGA TRINZA is encompassed within the exposure range for the approved dose strengths of paliperidone extended-release tablets. The between-subject variability for paliperidone pharmacokinetics following delivery from INVEGA TRINZA was similar to the variability for paliperidone extended-release tablets.
Because of the difference in median pharmacokinetic profiles among the three formulations, caution should be e… [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 The efficacy of INVEGA TRINZA for the treatment of schizophrenia in patients who have been adequately treated for at least 4 months with INVEGA SUSTENNA (1-month paliperidone palmitate extended-release injectable suspension) was evaluated in a long-term double-blind, placebo-controlled randomized-withdrawal trial designed to evaluate time to relapse involving adult subjects who met DSM-IV-TR criteria for schizophrenia. Patients could enter the study with acute symptoms (if previously treated with oral antipsychotics) or be clinically stable (if treated with long-acting injectable antipsychotics [LAI]).
All patients who previously received oral antipsychotics received the paliperidone palmitate 1-month initiation regimen (deltoid injections of 234 mg and 156 mg one week apart), while those patients switching from LAI medication were treated with the 1-month paliperidone palmitate extended-release injectable suspension in place of the next scheduled injection. Specifically: For patients entering the study who were already being treated with the 1-month paliperidone palmitate extended-release injectable suspension, their dosing remained unchanged.
Patients who were currently receiving the 39 mg dose of 1-month paliperidone palmitate were not eligible to enroll in the study. Patients entering the study who were being treated with 25 mg, 37.5 mg, or 50 mg of RISPERDAL CONSTA (risperidone long-acting injection) were switched to 78 mg, 117 mg, or 156 mg, respectively, of the 1-month paliperidone palmitate administered in the deltoid muscle. Patients entering the study who were being treated with any other LAI product were switched to 234 mg of the 1-month paliperidone palmitate administered in the deltoid muscle.
This study consisted of the following three treatment periods: A 17-week flexible-dose open-label period with the 1-month paliperidone palmitate (first part of a 29-week open-label stabilization phase). A total of 506 patients entered this phase of the study. Dosing of the 1-month paliperidone palmitate was individualized based on symptom response, tolerability, and previous medication history.
Specifically, the dose could be adjusted at the week 5 and 9 injections and the injection site could be deltoid or gluteal. The week 13 dose had to be the same as the week 9 dose. Patients had to be clinically stable at the end of this period before receiving INVEGA TRINZA at the week 17 visit.
Clinical stability was defined as achieving a PANSS total score <70 at week 17. 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. A 12-week open-label treatment period with INVEGA TRINZA (second part of a 29-week open-label stabilization phase).
A total of 379 patients received a single-dose of INVEGA TRINZA which was a 3.5 multiple of the last dose of the 1-month paliperidone palmitate. Patients had to remain clinically stable before entry into the next period (double-blind). Clinical stability was defined as achieving a PANSS total score <70 and scores of ≤ 4 for seven specific PANSS items.
A variable length double-blind treatment period. In this period, 305 stabilized patients were randomized 1:1 to continue treatment with INVEGA TRINZA or placebo until relapse, early withdrawal, or the end of study. Patients were randomized to the same dose of INVEGA TRINZA they received during the open-label phase (i.e., 273 mg, 410 mg, 546 mg, or 819 mg) or to placebo administered every 12 weeks.
The numbers (%) of patients entering double-blind on each of the dose levels were 6 (4%) for 273 mg, 15 (9%) for 410 mg, 78 (49%) for 546 mg, and 61 (38%) for 819 mg. The primary efficacy variable was time to first relapse. Relapse was pre-defined as emergence of one or more of the following: psychiatric hospitalization, ≥ 25% in… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance INVEGA TRINZA (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 TRINZA (paliperidone) is not a controlled substance.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No carcinogenicity studies were conducted with the 3-month paliperidone palmitate extended-release injectable suspension. The carcinogenic potential of intramuscularly injected 1-month paliperidone palmitate extended-release injectable suspension 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 0.2, 0.6, and 1 times, respectively, the MRHD of 819 mg of INVEGA TRINZA 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 0.6 and 1 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 D2 antagonism and hyperprolactinemia.
The relevance of these tumor findings in rodents to human risk is unclear [see Warnings and Precautions (5.7) ]. Mutagenesis No mutagenesis studies were conducted with the 3-month paliperidone palmitate extended-release injectable suspension. 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 the 3-month paliperidone palmitate extended-release injectable suspension. 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).
13.2Animal Toxicology and/or Pharmacology Injection site toxicity was assessed in minipigs injected intramuscularly with the 3-month paliperidone palmitate extended-release injectable suspension at doses up to 819 mg, which is equal to the MRHD. Injection site inflammatory reactions we… [Excerpted — this section continues on DailyMed.]
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis No carcinogenicity studies were conducted with the 3-month paliperidone palmitate extended-release injectable suspension. The carcinogenic potential of intramuscularly injected 1-month paliperidone palmitate extended-release injectable suspension 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 0.2, 0.6, and 1 times, respectively, the MRHD of 819 mg of INVEGA TRINZA 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 0.6 and 1 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 D2 antagonism and hyperprolactinemia.
The relevance of these tumor findings in rodents to human risk is unclear [see Warnings and Precautions (5.7) ]. Mutagenesis No mutagenesis studies were conducted with the 3-month paliperidone palmitate extended-release injectable suspension. 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 the 3-month paliperidone palmitate extended-release injectable suspension. 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 TRINZA ® (in-VAY-guh TRIN-zuh) (paliperidone palmitate) Extended-Release Injectable Suspension What is the most important information I should know about INVEGA TRINZA ?
INVEGA TRINZA 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 TRINZA is not for treating dementia-related psychosis. What is INVEGA TRINZA ?
INVEGA TRINZA is a prescription medicine given by injection by a healthcare professional and used to treat schizophrenia. INVEGA TRINZA is used in people who have been treated with INVEGA SUSTENNA 1 time a month injections for at least 4 months. It is not known if INVEGA TRINZA is safe and effective in children under 18 years of age.
Who should not receive INVEGA TRINZA ? Do not receive INVEGA TRINZA if you: are allergic to paliperidone palmitate, risperidone, or any of the ingredients in INVEGA TRINZA. See the end of this Patient Information leaflet for a complete list of ingredients in INVEGA TRINZA.
What should I tell my healthcare provider before receiving INVEGA TRINZA ? Before you receive INVEGA TRINZA, 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 TRINZA will harm your unborn baby. If you become pregnant while taking INVEGA TRINZA, 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 TRINZA 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 TRINZA can pass into your breast milk.
Talk to your healthcare provider about the best way to feed your baby if you receive INVEGA TRINZA. 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 TRINZA ? Follow your INVEGA TRINZA treatment schedule exactly as your healthcare provider tells you to.
Your healthcare provider will tell you how much INVEGA TRINZA you will receive and when you will receive it. INVEGA TRINZA is given as an injection by your healthcare provider into the muscle (intramuscularly) of your arm or your buttocks, 1 time every 3 months. What should I avoid while receiving INVEGA TRINZA ?
INVEGA TRINZA 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 know how INVEGA TRINZA affects you. Avoid getting overheated or dehydrated.
What are the possible side effects of INVEGA TRINZA ? INVEGA TRINZA may cause serious side effects, including: See " What… [Excerpted — this section continues on DailyMed.]
📖 Instructions for Use ▾
2.8Instructions for Preparation and Administration Administer every 3 months Shake syringe vigorously for at least 15 seconds For intramuscular injection only. Do not administer by any other route. Important INVEGA TRINZA should be administered by a healthcare professional as a single injection.
DO NOT divide dose into multiple injections. INVEGA TRINZA is intended for intramuscular use only. Inject slowly, deep into the muscle taking care to avoid injection into a blood vessel.
Read complete instructions prior to use. Dosing This medication should be administered once every 3 months . Preparation Peel off tab label from the syringe and place in patient record.
INVEGA TRINZA requires longer and more vigorous shaking than INVEGA SUSTENNA (1-month paliperidone palmitate extended-release injectable suspension). Shake the syringe vigorously, with the syringe tip pointing up, for at least 15 seconds within 5 minutes prior to administration (see Step 2 ). Thin Wall Safety Needle Selection Thin wall safety needles are designed to be used with INVEGA TRINZA.
Therefore, it is important to only use the needles provided in the INVEGA TRINZA kit . Dose pack contents Prefilled Syringe Thin Wall Safety Needles 1 Select needle Needle selection is determined by injection area and patient weight. If administering a Deltoid injection If patient weighs: Less than 90 kg pink hub If administering a Gluteal injection If patient weighs: Less than 90 kg yellow hub 90 kg or more yellow hub 90 kg or more yellow hub 2 Prepare for injection Check suspension After shaking the syringe for at least 15 seconds, check the liquid in the viewing window.
The suspension should appear uniform and milky white in color. It is also normal to see small air bubbles. Open needle pouch and remove cap First, open needle pouch by peeling the cover back half way.
Place on a clean surface. Then, holding the syringe upright, twist and pull the rubber cap to remove. Grasp needle pouch Fold back needle cover and plastic tray.
Then, firmly grasp the needle sheath through the pouch, as shown. Attach needle 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 leakage prior to administration. Remove needle sheath Pull the needle sheath away from the needle in a straight motion. Do not twist the sheath, as this may loosen the needle from the syringe.
Remove air bubbles Hold the syringe upright and tap gently to make any air bubbles rise to the top. Remove air by pressing the plunger rod upward carefully until a drop of liquid comes out of the needle tip. 3 Inject Inject dose Slowly inject the entire contents of the syringe intramuscularly, deep into the selected deltoid or gluteal muscle.
Do not administer by any other route. 4 After injection Secure needle After the injection is complete, use your thumb or a flat surface to secure the needle in the safety device. The needle is secure when a "click" sound is heard.
Dispose properly Dispose of the syringe and unused needle in an approved sharps container. Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image
Instructions for Use INVEGA TRINZA ® paliperidone palmitate extended-release injectable suspension Administer every 3 months Shake syringe vigorously for at least 15 seconds For intramuscular injection only. Do not administer by any other route. Important INVEGA TRINZA should be administered by a healthcare professional as a single injection.
DO NOT divide dose into multiple injections. INVEGA TRINZA is intended for intramuscular use only. Inject slowly, deep into the muscle taking care to avoid injection into a blood vessel.
Read complete instructions prior to use. Dosing This medication should be administered once every 3 months . Preparation Peel off tab label from the syringe and place in patient record.
INVEGA TRINZA requires longer… [Excerpted — this section continues on DailyMed.]
📄 Recent Major Changes ▾
Dosage and Administration ( 2.5 , 2.8 ) 9/2024 Warnings and Precautions ( 5.10 ) 1/2025
📄 Package Label / Principal Display Panel ▾
PRINCIPAL DISPLAY PANEL - 273 mg Syringe Carton 3 MONTHS Administer every 3 months Shake syringe vigorously for at least 15 seconds 273 mg Each single-dose prefilled syringe contains 273 mg (0.88 mL) paliperidone palmitate. NDC 50458-606-01 Single-dose prefilled syringe. Use entire contents of syringe.
INVEGA TRINZA ® 273 mg paliperidone palmitate extended-release injectable suspension FOR INTRAMUSCULAR INJECTION ONLY Each injection must be administered only by a health care professional. Shake before using CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1-inch thin wall safety needle and a 22G, 1½-inch thin wall safety needle) For recommended dosing instructions, please see accompanying full Package Insert. Rx only Store at room temperature 20°C to 25°C; (68°F to 77°F); excursions between 15°C to 30°C (59°F to 86°F) are permitted. janssen PRINCIPAL DISPLAY PANEL - 273 mg Syringe Carton
PRINCIPAL DISPLAY PANEL - 410 mg Syringe Carton 3 MONTHS Administer every 3 months Shake syringe vigorously for at least 15 seconds 410 mg Each single-dose prefilled syringe contains 410 mg (1.32 mL) paliperidone palmitate. NDC 50458-607-01 Single-dose prefilled syringe. Use entire contents of syringe.
INVEGA TRINZA ® 410 mg paliperidone palmitate extended-release injectable suspension FOR INTRAMUSCULAR INJECTION ONLY Each injection must be administered only by a health care professional. Shake before using CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1-inch thin wall safety needle and a 22G, 1½-inch thin wall safety needle) For recommended dosing instructions, please see accompanying full Package Insert. Rx only Store at room temperature 20°C to 25°C; (68°F to 77°F); excursions between 15°C to 30°C (59°F to 86°F) are permitted. janssen PRINCIPAL DISPLAY PANEL - 410 mg Syringe Carton
PRINCIPAL DISPLAY PANEL - 546 mg Syringe Carton 3 MONTHS Administer every 3 months Shake syringe vigorously for at least 15 seconds 546 mg Each single-dose prefilled syringe contains 546 mg (1.75 mL) paliperidone palmitate. NDC 50458-608-01 Single-dose prefilled syringe. Use entire contents of syringe.
INVEGA TRINZA ® 546 mg paliperidone palmitate extended-release injectable suspension FOR INTRAMUSCULAR INJECTION ONLY Each injection must be administered only by a health care professional. Shake before using CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1-inch thin wall safety needle and a 22G, 1½-inch thin wall safety needle) For recommended dosing instructions, please see accompanying full Package Insert. Rx only Store at room temperature 20°C to 25°C; (68°F to 77°F); excursions between 15°C to 30°C (59°F to 86°F) are permitted. janssen PRINCIPAL DISPLAY PANEL - 546 mg Syringe Carton
PRINCIPAL DISPLAY PANEL - 819 mg Syringe Carton 3 MONTHS Administer every 3 months Shake syringe vigorously for at least 15 seconds 819 mg Each single-dose prefilled syringe contains 819 mg (2.63 mL) paliperidone palmitate. NDC 50458-609-01 Single-dose prefilled syringe. Use entire contents of syringe.
INVEGA TRINZA ® 819 mg paliperidone palmitate extended-release injectable suspension FOR INTRAMUSCULAR INJECTION ONLY Each injection must be administered only by a health care professional. Shake before using CONTENTS: 1 single-dose prefilled syringe and 2 needles (a 22G, 1-inch thin wall safety needle and a 22G, 1½-inch thin wall safety needle) For recommended dosing instructions, please see accompanying full Package Insert. Rx only Store at room temperature 20°C to 25°C; (68°F to 77°F); excursions between 15°C to 30°C (59°F to 86°F) are permitted. janssen PRINCIPAL DISPLAY PANEL - 819 mg Syringe Carton
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