DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 39, 78, 117, 156 and 234 mg of paliperidone palmitate are equal to 25, 50, 75, 100 and 150 mg eq. of paliperidone, respectively.
• INVEGA TRINZA doses expressed as 273, 410, 546 and 819 mg of paliperidone palmitate are equal to 175, 263, 350 and 525 mg eq. of paliperidone, respectively.

dosing information

Dose Optimization with INVEGA SUSTENNA

• Prior to initiating INVEGA TRINZA, patients must be adequately treated with INVEGA SUSTENNA for at least 4 months. The selection of an optimal dose of INVEGA SUSTENNA is based on individual patient’s schizophrenia symptoms, patient tolerability of INVEGA SUSTENNA, and knowledge of prior antipsychotic doses. Appropriate time for transition from INVEGA SUSTENNA to INVEGA TRINZA should be based on clinical judgment with consideration toward balancing efficacy and safety.¹
• Due to the slow release characteristics of INVEGA TRINZA, the product is not intended to be used for initiation of treatment in acutely symptomatic patients or in patients who are immediately transitioning from oral to long-acting injectable antipsychotic therapy. Rather, INVEGA TRINZA is intended to be used in patients who have already demonstrated a therapeutic effect and ability to tolerate INVEGA SUSTENNA over a treatment period of at least 4 months at the time of initiation of INVEGA TRINZA.¹
• Appropriate initiation and stabilization with INVEGA SUSTENNA prior to transitioning to INVEGA TRINZA is important for the following reasons¹:
  • Patients may be transitioned to an inappropriate dose of INVEGA TRINZA, resulting in either relapse (if dose is too low) or adverse events (if dose is too high).¹
  • Due to the long half-life of INVEGA TRINZA, it may take as long as 1 year for paliperidone palmitate plasma concentrations to achieve therapeutic levels.¹
  • Additional patient factors that slow the drug absorption process, such as high body mass index, female gender, and gluteal initiation, may further prolong the time to reach therapeutic concentrations.¹
  • Due to the long-acting nature of INVEGA TRINZA, it is inefficient to attempt to stabilize patients directly on this product; if any dose adjustments are necessary, the effects will not be apparent for several months.¹

Turkoz et al (2022)⁴ conducted a retrospective cohort study that evaluated the real-world data on relapse rates in adult patients with schizophrenia who transitioned to INVEGA TRINZA after adequate treatment (AT) vs not adequate treatment (NAT) with INVEGA SUSTENNA.

Study Design/Methods

• Data were derived from the IBM^® MarketScan^® Multi-State Medicaid Database (June 2015-December 2020).
• Propensity score matching was conducted on the basis of patient demographics and disease state characteristics for the AT and NAT cohorts.
  • AT cohort included patients who were treated with INVEGA SUSTENNA for ≥4 months (≥5 injections), wherein the last 2 doses of INVEGA SUSTENNA were same, and the INVEGA TRINZA initiation dose met the corresponding dose conversion from INVEGA SUSTENNA to INVEGA TRINZA.
  • NAT cohort included patients who received ≤2 or no INVEGA SUSTENNA doses.
• Additionally, 2 sensitivity analyses based on duration of follow-up (≥6 and ≥24 months) were conducted that assessed the robustness of the main analysis.

Results

• After propensity score matching, 657 patients were included in each cohort.
• The relapse rate was significantly lower in the AT vs NAT cohort (18.4% vs 26.8%; P=0.0002).
• The risk to relapse decreased by 35% (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51-0.81) in the AT vs NAT cohort.
• The most common reason for relapse in each cohort was inpatient psychiatric hospitalization.

Sensitivity Analysis

• After propensity score matching, 765 and 455 patients were included in each cohort in the first and second sensitivity analysis, respectively.
• The relapse rates were consistent in both analyses. A significantly lower relapse rate was observed in the AT vs NAT cohort (P=0.0002 vs P=0.0292).
• In the first and second sensitivity analyses, the risk to relapse was lower by 33% (HR, 0.67; 95% CI, 0.54-0.83) and 26% (HR, 0.74; 95% CI, 0.56-0.97), respectively, in the AT vs NAT cohort.
• In the first and sensitivity analyses, the most common reason for relapse was inpatient psychiatric hospitalization in both cohorts.

Limitations

• The claims data may not have completely captured all the medical conditions and outcomes.
• Missing data or varying levels of coding practices among providers.
• Analysis was restricted to first relapse; therefore, assessment of annualized relapse rates was not possible.

O’Donnell et al (2019)^5,6 conducted a post-hoc analysis of the relapse prevention study to further define “adequately treated” by identifying which patient characteristics were associated with successful transition from INVEGA SUSTENNA to INVEGA TRINZA.

Study Design/Methods

• Comparisons were made between the group of patients who met randomization criteria to transition to INVEGA TRINZA (randomized group) vs those who did not meet randomization criteria (nonrandomized group).

Results

• Using a stepwise logistic regression model, multiple baseline clinical factors were identified to predict readiness for transition from INVEGA SUSTENNA to INVEGA TRINZA, including fewer (3 vs 0) prior hospitalizations for psychosis (odds ratio [OR], 0.39; 95% CI, 0.19-0.84), lower baseline Clinical Global Impression-Severity (CGI-S) scores (OR, 0.66; 95% CI, 0.48-0.90), and shorter duration of illness at baseline (OR, 0.97; 95% CI, 0.95-1.00).

Nash et al (2017)^7,8 conducted a post-hoc analysis of the non-inferiority study to identify patient characteristics during INVEGA SUSTENNA treatment that would result in a greater likelihood of achieving symptomatic remission after transitioning to INVEGA TRINZA.

Study Design/Methods

• Remission was defined as a score of ≤3 on Positive and Negative Syndrome Scale (PANSS) items P1, G9, P3, P2, G5, N1, N4, and N6 maintained for ≥6 months.

Results

• Among 411 patients in the INVEGA TRINZA group who had completed 6 months of follow-up and were included in the analysis, 260 (63.3%) patients achieved remission.
• Patients who had larger improvements in CGI, PANSS, and Personal and Social Performance (PSP) scores over the 17-week open-label treatment phase with INVEGA SUSTENNA were more likely to achieve remission once they transitioned to INVEGA TRINZA in the double-blind phase (P<0.05).
• Furthermore, early improvement in CGI (P=0.006) and PANSS (P<0.001) starting at Week 5 and maintained through week 17, increased the likelihood of achieving remission after transition to INVEGA TRINZA.

Dose Initiation

• Initiate INVEGA TRINZA when the next 1-month paliperidone palmitate dose is scheduled with a INVEGA TRINZA dose based on the previous 1-month injection dose, using the equivalent 3.5-fold higher dose (see Table: INVEGA TRINZA Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA).¹

Management of a Missed Dose:

• Missing doses of INVEGA TRINZA should be avoided. Patients may be given the injection up to 2 weeks before or after the 3-month time point.¹
• Missed Dose >3½ Months to <4 Months Since Last Injection: The previously administered INVEGA TRINZA dose should be administered as soon as possible, then continue with the 3-month injections following this dose.¹
• Missed Dose 4 Months to 9 Months Since Last Injection: Do NOT administer the next dose of INVEGA TRINZA. Instead, reinitiate the regimen using the Table: ReInitiation Regimen After Missing 4 Months to 9 Months of INVEGA TRINZA.¹
• Missed Dose >9 Months Since Last Injection: Re-initiate treatment with the 1month paliperidone palmitate extended-release injectable suspension as described in the prescribing information for that product. INVEGA TRINZA can then be resumed after the patient has been adequately treated with INVEGA SUSTENNA for at least 4 months.¹

INTERCHANGEABILITY OF INJECTION SITES

Pharmacokinetic simulations found that after steady state was achieved with the PP3M formulation, C_max and C_min were not significantly different between injection sites in the deltoid or the gluteal muscle (11% to 12% higher for deltoid muscle).³ Therefore, INVEGA TRINZA may be administered in either site (deltoid or gluteal) at any given time according to the recommended scheduled regimen.¹

OTHER RELEVANT LITERATURE

A citation for a review article summarizing the pharmacokinetic rationale for the dosing and switching strategies for INVEGA TRINZA is provided in the References section below.⁹

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 19 January 2024.