Coverage Policy Manual
Policy #: 2016021
Category: Pharmacy
Initiated: August 2016
Last Review: August 2023
  Paliperidone Palmitate (e.g., Long-acting Injectables Invega Sustenna ® & Invega Trinza)
Description:
Paliperidone palmitate is the primary active metabolite of the older antipsychotic risperidone.  Paliperidone palmitate (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications.  Paliperidone palmitate is also active as an antagonist at alpha 1 and alpha 2 adrenergic receptors and H1 histaminergic receptors, which may explain some of the other effects of the drug. Paliperidone palmitate was approved by the FDA for treatment of schizophrenia on December 20, 2006. Invega is an extended release formulation of paliperidone palmitate that uses the OROS extended release system to allow for once-daily dosing developed by Janssen Pharmaceutical.
 
Paliperidone palmitate (trade name Invega Sustenna, named Xeplion in Europe and other countries) is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-monthly injection after an initial titration period with an oral form of paliperidone.
 
Regulatory Status
 
A new formulation of paliperidone palmitate was approved the FDA on May 18, 2015 under the brand name of Invega Trinza as an extended-release injectable suspension for 3 months as indicated for 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.
 
Coding
 
See CPT/HCPCS Code section below.
 
Policy/
Coverage:
Effective April 01, 2022 Prior Approval is required for Paliperidone.
 
The Step Therapy Medication Act is applicable to fully-insured (Arkansas Blue Cross, Health Advantage, and Exchange) and specified governmental (ASE/PSE and ASP) health plans. The law is not applicable to FEP or self-insured ERISA groups (including but not limited to Walmart, Tyson or other Blue Advantage groups). Initial approval for exigent request is 28 days. Otherwise, initial approval for standard review is up to 1 year.
 
Effective August 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate (e.g., Invega Sustenna) as a monthly formulation meets member benefit certificate primary coverage criteria for the treatment of:
 
    1. Schizophrenia
    2. Schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months when the below criteria are met:
 
    1. Documentation of tolerability has been established with oral paliperidone or oral risperidone (Schreiner, 2016; APA, 2020); AND
    2. The individual has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; APA, 2020); AND
    3. Individual is at least 18 years of age AND
    4. Must be dosed in accordance with the FDA label.
 
The use of long-acting injectable paliperidone palmitate (e.g., Invega Trinza) as a 3-month formulation meets member benefit certificate primary coverage criteria for the treatment of adults with schizophrenia when the below criteria are met:
 
INITIAL APPROVAL for up to 12 months:
 
    1. Documentation of tolerability to a 1 month formulation of long-acting paliperidone extended-release injectable for at least 4 months (Savitz, 2016; APA, 2020); AND
    2. The individual has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; Savitz, 2016; APA, 2020); AND
    3. Individual is at least 18 years of age AND
    4. Must be dosed in accordance with the FDA label.
 
CONTINUATION OF THERAPY for 12 months:
 
1. Individual meets criteria for initial approval based on indication.
2. Individual has experienced a positive clinical response to paliperidone palmitate.
3. Must be dosed in accordance with FDA label.
 
Dosage and Administration
Dosing per FDA Guidelines
 
Paliperidone palmitate (e.g., Invega Sustenna)
    • Each injection must be administered only by a healthcare professional.
    • The recommended dosing for Schizophrenia:
        • Initiation Dosing
            • Day 1: 234 mg
            • Day 8: 156 mg
            • Monthly Maintenance Dose: 39-234 mg (234 mg maximum monthly dose)
    • The recommended dosing for Schizoaffective disorder:
        • Initiation Dosing
            • Day 1: 234 mg
            • Day 8: 156 mg
            • Monthly Maintenance Dose: 78-234 mg (234 mg maximum monthly dose)
    • Paliperidone palmitate (e.g., Invega Sustenna) extended-release injectable suspension is available as 39 mg/0.25 mL, 78 mg/0.5 mL, 117 mg/0.75 mL, 156 mg/mL, or 234 mg/1.5 mL.
 
Paliperidone palmitate (e.g., Invega Trinza)
    • Use only after the individual has been adequately treated with the 1-month paliperidone palmitate extended-release injectable suspension for at least four months.
    • Should be administered once every 3 months.
    • Each injection must be administered only by a healthcare professional.
    • The recommended dose is:
        • If the last dose of paliperidone palmitate (e.g., Invega Sustenna) is 78 mg initiate paliperidone palmitate (e.g., Invega Trinza) at 273 mg.
        • If the last dose of paliperidone palmitate (e.g., Invega Sustenna) is 117 mg initiate paliperidone palmitate (e.g., Invega Trinza) at 410 mg.
        • If the last dose of paliperidone palmitate (e.g., Invega Sustenna) is 156 mg initiate paliperidone palmitate (e.g., Invega Trinza) at 546 mg.
        • If the last dose of paliperidone palmitate (e.g., Invega Sustenna) is 234 mg initiate paliperidone palmitate (e.g., Invega Trinza) at 819 mg.
    • Paliperidone palmitate (e.g., Invega Trinza) extended-release injectable suspension is available as 273 mg/0.88 mL, 410 mg/1.32 mL, 546 mg/175 mL, or 819 mg/2.63 mL.  
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate for any indication or circumstance other than those described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For individuals with contracts without primary coverage criteria the use of long-acting injectable paliperidone palmitate for any indication or circumstance other than those described above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of Invega Sustenna is not FDA approved for dementia-related psychosis and does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For individuals with contracts without primary coverage criteria the use Invega Sustenna is not FDA approved for dementia related psychosis and is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective August 2022 to July 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate (e.g., Invega Sustenna) as a monthly formulation meets member benefit certificate primary coverage criteria for the treatment of:
 
    1. schizophrenia
    2. schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months when the below criteria are met:
 
    1. Documentation of tolerability has been established with oral paliperidone or oral risperidone (Schreiner, 2016; APA, 2020); AND
    2. The individual has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; APA, 2020); AND
    3. Individual is at least 18 years of age AND
    4. Must be dosed in accordance with the FDA label unless otherwise specified.
 
The use of long-acting injectable paliperidone palmitate (e.g., Invega Trinza) as a 3-month formulation meets member benefit certificate primary coverage criteria for the treatment of adults with schizophrenia when the below criteria are met:
 
INITIAL APPROVAL for up to 12 months:
 
    1. Documentation of tolerability to a 1 month formulation of long-acting paliperidone extended-release injectable for at least 4 months (Savitz, 2016; APA, 2020); AND
    2. The individual has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; Savitz, 2016; APA, 2020); AND
    3. Individual is at least 18 years of age AND
    4. Must be dosed in accordance with the FDA label unless otherwise specified.
 
CONTINUATION OF THERAPY for 12 months:
 
1. Individual meets criteria for initial approval based on indication.
2. Individual has experienced a positive clinical response to paliperidone palmitate.
3. Must be dosed in accordance with FDA label unless otherwise specified.
 
Dosage and Administration
 
    1. Per FDA label guidelines
    2. Each injection must be administered only by a healthcare professional.  
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate for any other indication than those listed above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For individuals with contracts without primary coverage criteria the use of long-acting injectable paliperidone palmitate for any other indication than those listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of Invega Sustenna is not FDA approved for dementia-related psychosis and does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For individuals with contracts without primary coverage criteria the use Invega Sustenna is not FDA approved for dementia related psychosis and is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective April 1, 2022 to July 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate (Invega Sustenna) as a monthly formulation meets member benefit certificate primary coverage criteria for the treatment of:
 
    • schizophrenia
    • schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months when the below criteria are met:
 
    • Documentation of tolerability has been established with oral paliperidone or oral risperidone (Schreiner, 2016; APA, 2020); AND
    • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; APA, 2020); AND
    • Member is at least 18 years of age.
 
The use of long-acting injectable paliperidone palmitate (Invega Trinza) as a 3 month formulation meets member benefit certificate primary coverage criteria for the treatment of adults with schizophrenia when the below criteria are met:
 
INITIAL APPROVAL for up to 12 months:
 
    • Documentation of tolerability to a 1 month formulation of long-acting paliperidone extended-release injectable for at least 4 months (Savitz, 2016; APA, 2020); AND
    • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; Savitz, 2016; APA, 2020); AND
    • Member is at least 18 years of age.
 
CONTINUATION OF THERAPY for 12 months:
1. Member meets criteria for initial approval based on indication.
2. Member has experienced a positive clinical response to paliperidone palmitate.
3. Dosed in accordance with FDA labeling.
 
Dosage and Administration
 
    • Per FDA label guidelines
    • Each injection must be administered only by a healthcare professional.  
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate for any other indication than those listed above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria the use of long-acting injectable paliperidone palmitate for any other indication than those listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of Invega Sustenna is not FDA approved for dementia-related psychosis and does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria the use Invega Sustenna is not FDA approved for dementia related psychosis and is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective August 2020 to March 31, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate (Invega Sustenna) as a monthly formulation meets member benefit certificate primary coverage criteria for the treatment of:
 
    • schizophrenia
    • schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers or antidepressants
 
when the below criteria are met:
 
    • Documentation of tolerability has been established with oral paliperidone or oral risperidone (Schreiner, 2016; APA, 2020); AND
    • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; APA, 2020); AND
    • Member is at least 18 years of age.
 
The use of long-acting injectable paliperidone palmitate (Invega Trinza) as a 3 month formulation meets member benefit certificate primary coverage criteria for the treatment of adults with schizophrenia when the below criteria are met:
 
    • Documentation of tolerability to a 1 month formulation of long-acting paliperidone extended-release injectable for at least 4 months (Savitz, 2016; APA, 2020); AND
    • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach (Kim, 2016; Savitz, 2016; APA, 2020); AND
    • Member is at least 18 years of age.
 
Dosage and Administration
 
    • Per FDA label guidelines
    • Each injection must be administered only by a healthcare professional.  
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate for any other indication than those listed above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria the use of long-acting injectable paliperidone palmitate for any other indication than those listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
The use of Invega Sustenna is not FDA approved for dementia-related psychosis and does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
 
For members with contracts without primary coverage criteria the use Invega Sustenna is not FDA approved for dementia related psychosis and is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective 8/26/2016 to July 2019
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate (Invega Sustenna) as a monthly formulation meets member benefit certificate primary coverage criteria for the treatment of schizophrenia when the below criteria are met:
      • Documentation of tolerability has been established with oral paliperidone or oral risperidone; AND
      • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach; AND
      • Member is at least 18 years of age; AND
      • Dosage, frequency, and dose initiation conversions between different formulations are within the FDA-approved range
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
The use of long-acting injectable paliperidone palmitate as a 3 month formulation meets member benefit certificate primary coverage criteria for the treatment of schizophrenia when the below criteria are met:
      • Documentation of tolerability to a 1 month formulation of long-acting paliperidone extended-release injectable for at least 4 months; AND
      • The member has a history of noncompliance with oral antipsychotics resulting in decompensation, or a rationale is provided indicating why the member requires an injection approach; AND
      • Member is at least 18 years of age; AND
      • Dosage, frequency, and dose initiation conversions between different formulations must be within the FDA-approved range.
 
NOTE:  Initial coverage duration will be for 12 months.  Additional coverage after each 12 months period will require documentation indicating the patient has clinically benefited from treatment and remained compliant.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of long-acting injectable paliperidone palmitate for any other indication than those listed above does not meet member benefit certificate primary coverage criteria.
 
For members with contracts without primary coverage criteria the use of long-acting injectable paliperidone palmitate for any other indication than those listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
Alphs et al published a multicenter  15-month clinical trial of 450 patients with schizophrenia, who had been taken into custody by the criminal justice system at least two times in the previous two years, randomly assigned them to open-label treatment with paliperidone-LAI or one of seven daily oral antipsychotics. The primary end point was time to treatment failure, which included arrest/incarceration, psychiatric hospitalization, suicide, inadequate efficacy, discontinuation due to tolerability, or increased services to prevent imminent hospitalization. After 15 months, fewer subjects receiving paliperidone-LAI experienced treatment failure compared to patients receiving oral antipsychotics (39.8 versus 53.7 percent). Median time to first treatment failure was longer for paliperidone-LAI compared oral antipsychotics (416 versus 226 days). The most common reasons for treatment failure were arrest/incarceration and psychiatric hospitalization. No differences were seen between groups on measures of social functioning or severity of illness. Patients taking paliperidone-LAI were more likely to experience extrapyramidal symptoms, weight gain, and prolactin elevation compared with patients taking oral antipsychotic drugs. Medication adherence rates, to the extent that they could be measured or estimated, were higher in the paliperidone-LAI compared with oral antipsychotics as measured by prescriptions or pharmacy refills (95.2 versus 77.2 or 24.3 percent).
 
2018 Update
A literature search conducted using the MEDLINE database did not reveal any new
literature that would prompt a change in the coverage statement.
 
 2017 Update
A literature search conducted using the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement.
 
2019 Update
A literature search conducted through July 2019 did not reveal any new information that would prompt a change in the coverage statement.
 
2020 Update
Data from two multinational, double-blind (DB), randomized, controlled phase 3 studies including patients with schizophrenia (DSM-IV-TR) previously stabilized on paliperidone palmitate (PP1M/PP3M) (open-label [OL] phase) was analyzed for efficacy and safety. Patients were randomized to PP3M or PP1M (noninferiority study A) and PP3M or placebo (study B) in DB phase. The subgroup analysis included Latin American (Argentina, Brazil, Colombia, Mexico) patients. Primary efficacy endpoints were relapse-free rates (study A) and time-to-relapse (study B).
In study A, 63/71 (88.7%) and in study B 38/43 (88.4%) Latin American patients completed the DB phase. In study A, relapse-free percentage was similar in Latin America (PP3M: 97%, PP1M: 100%) and ROW (PP3M: 91%, PP1M: 89%). In study B, median time-to-relapse was not estimable in the Latin American subgroup for either placebo or PP3M groups, nor for the ROW PP3M group; the median time-to-relapse in the ROW placebo group was 395 days. Caregiver burden improved in patients switching from oral antipsychotics (OL baseline) to PP3M/PP1M in DB phase (Involvement Evaluation Questionnaire score mean ± SD change, -9.4±15.16; p < 0.001). Treatment emergent adverse events with PP3M during DB phase were similar in Latin America (study A: 24/34 [70.6%]; study B: 15/21 [71.4%]) and ROW (study A: 318/470 [67.7%]; study B: 84/139 [60.4%]) subgroups.
PP3M was efficacious and showed no new safety concerns in patients with schizophrenia from Latin America, corroborating ROW findings. (Savitz AJ, Xu H, Gopal S, Nuamah I, Mathews M, Soares B., 2019)
 
2021 Update
A double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18-70 years) with schizophrenia, previously stabilized on PP1M.
 
After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase.
 
Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected.
 
Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia. (Savitz AJ, Xu H, Gopal S, et.al., 2016)
 
An analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).
 
PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.
 
Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.
 
Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results. (Kim E, Correll CU, Mao L, et.al., 2016)
 
A study aimed to explore the safety, tolerability, and treatment response of paliperidone palmitate once-monthly in non-acute but symptomatic adult patients switched from previously unsuccessful monotherapy with frequently used oral atypical antipsychotics.
 
This was a post hoc analysis of a prospective, interventional, single-arm, international, multicenter, open-label, 6-month study.
 
The patients (N = 472) were switched to paliperidone palmitate once-monthly (PP1M) from daily oral treatment with either aripiprazole (n = 46), olanzapine (n = 87), paliperidone extended-release (n = 104), quetiapine (n = 44), or risperidone (n = 191). In all groups, mean Positive and Negative Syndrome Scale total (p < 0.0001) and Clinical Global Impression-Severity scores improved significantly (p = 0.0004 to p < 0.0001). An improvement of ≥50 % in the Positive and Negative Syndrome Scale total score was observed in 21.7 % (aripiprazole), 29.9 % (olanzapine), 29.8 % (paliperidone extended-release), 27.3 % (quetiapine), and 37.2 % (risperidone) of patients. The patients showed significant improvements in the Personal and Social Performance score (aripiprazole p = 0.0409, all others p ≤ 0.0015); Mini International Classification of Functionality, Disability and Health Rating for Activity and Participation Disorders in Psychological Illnesses total scores (all p < 0.01); and Treatment Satisfaction Questionnaire for Medication Global Satisfaction score (olanzapine and risperidone p < 0.0001, quetiapine p = 0.0465, paliperidone extended-release p = 0.0571, aripiprazole p = NS). Paliperidone palmitate once-monthly was well tolerated, presenting no new safety signals.
 
These data illustrate that stable, non-acute but symptomatic patients on oral antipsychotic monotherapy may show clinically meaningful improvement of symptoms, functioning, and treatment satisfaction after direct transition to PP1M. The findings are limited by the naturalistic study design; thus, further studies are required to confirm the current findings. (Schreiner A, Caspi A, Bergmans P, et.al., 2016)
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through August 2023. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J2426Injection, paliperidone palmitate extended release, 1 mg
J2427Injection, paliperidone palmitate extended release (invega hafyera, or invega trinza), 1 mg
References: Alphs L, Benson C, Cheshire-Kinney K, et al.(2015) Real-world outcomes of paliperidone palmitate compared to daily oral antipsychotic therapy in schizophrenia: a randomized, open-label, review board-blinded 15-month study J Clin Psychiatry. 2015 May;76(5):554-61.

FDA Full Prescribing Information.(2016) Invega Sustenna. Accessed at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022264s019lbl.pdf. Last accessed Aug. 26, 2016.

FDA Full Prescribing Information.(2016) Invega Trinza. Accessed at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207946s001lbl.pdf. Last accessed Aug 26, 2016.

Kim E, Correll CU, Mao L, Starr HL, Alphs L.(2016) Once-monthly paliperidone palmitate compared with conventional and atypical daily oral antipsychotic treatment in patients with schizophrenia. CNS Spectr. 2016 Dec;21(6):466-477. doi: 10.1017/S1092852916000444. Epub 2016 Sep 15. PMID: 27629292.

Savitz AJ, Xu H, Gopal S, Nuamah I, Mathews M, Soares B.(2019) Efficacy and safety of paliperidone palmitate 3-month formulation in Latin American patients with schizophrenia: A subgroup analysis of data from two large phase 3 randomized, double-blind studies. Braz J Psychiatry. 2019;41(6):499-510. doi:10.1590/1516-4446-2018-0153

Savitz AJ, Xu H, Gopal S, Nuamah I, Ravenstijn P, Janik A, Schotte A, Hough D, Fleischhacker WW.(2016) Efficacy and Safety of Paliperidone Palmitate 3-Month Formulation for Patients with Schizophrenia: A Randomized, Multicenter, Double-Blind, Noninferiority Study Int J Neuropsychopharmacol. 2016 Jul 5;19(7):pyw018. doi: 10.1093/ijnp/pyw018. PMID: 26902950; PMCID: PMC4966278.

Schreiner A, Caspi A, Bergmans P, Cherubin P, Keim S, Lara E, Pinchuk I, Schuepbach D, Suleman S, Hargarter L.(2017) Switching from oral atypical antipsychotic monotherapy to paliperidone palmitate once-monthly in non-acute patients with schizophrenia: A prospective, open-label, interventional study. Psychopharmacology (Berl). 2017 Jan;234(1):3-13. doi: 10.1007/s00213-016-4445-0. Epub 2016 Nov 5. PMID: 27815602; PMCID: PMC5203852.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.