Summary

• INVEGA TRINZA is to be used only after the patient has been adequately treated with INVEGA SUSTENNA for at least 4 months. The last 2 doses of INVEGA SUSTENNA immediately before transition to INVEGA TRINZA should be the same.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 (LAI) 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
• A prospective, observational study evaluated the maintenance of clinical efficacy and tolerability, and variation of paliperidone plasma levels during the transition from INVEGA SUSTENNA to INVEGA TRINZA. After a slight initial increase, plasma levels were stabilized after the fourth administration of INVEGA SUSTENNA, and a slight reduction in plasma levels (not statistically significant) was observed during treatment with INVEGA TRINZA.²
• A multicenter, retrospective, observational study evaluated the effectiveness of INVEGA TRINZA among patients with schizophrenia who transitioned from INVEGA SUSTENNA to INVEGA TRINZA. INVEGA TRINZA treatment was initiated at the doses of 546 mg and 819 mg in 36.5% and 39.9% of patients, respectively. Majority of patients (90.8%) were transitioned from INVEGA SUSTENNA to INVEGA TRINZA at the conversion ratio of 3.5.³
• A double-blind (DB), placebo (PBO)-controlled, relapse-prevention study evaluated the efficacy and safety of INVEGA TRINZA-enrolled schizophrenia patients who were previously treated with oral antipsychotics and had acute symptoms or previously treated with LAI antipsychotic therapy and were clinically stable. An open-label (OL) phase preceded the DB phase, in which patients were stabilized with INVEGA SUSTENNA over 4 months before they received a dose of INVEGA TRINZA. Table: Dosing Details for Patients Converting From Previous Antipsychotics in a Clinical Trial describes how patients converted to INVEGA TRINZA from their previous antipsychotic regimen.⁴
  • For patients who had never taken oral paliperidone or oral or injectable risperidone, tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA was confirmed.

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 INVEGA SUSTENNA and INVEGA TRINZA 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.

CLINICAL STUDIES

Mauri et al (2022)² conducted a prospective, observational study to evaluate the maintenance of clinical efficacy and tolerability, and variation of paliperidone plasma levels during the transition from INVEGA SUSTENNA to INVEGA TRINZA.

Study Design/Methods

• Patients aged 18-66 years with schizophrenia were included, and observation was ongoing at the time of reporting.
• Clinical assessments were performed at the time of the first INVEGA SUSTENNA administration and then every 28 days up to the time of switching to INVEGA TRINZA, followed by 28 days and 2 months after the first INVEGA TRINZA administration and then every 3 months until 9 months of the first INVEGA TRINZA administration.
• All patients were stabilized on INVEGA SUSTENNA for 4 months and then switched to INVEGA TRINZA.

Results

• Overall, 22 patients were included (mean age, 46.91 years) in the study.
• The mean (standard deviation [SD]) plasma level of paliperidone was 32.84 (15.21) ng/mL at the time of transitioning from INVEGA SUSTENNA to INVEGA TRINZA and 23.56 (11.98) ng/mL 28 days after first INVEGA TRINZA administration.
• The plasma levels varied from a minimum of 16.40 ng/mL to a maximum of 30.22 ng/mL for INVEGA SUSTENNA, and from a minimum of 19.09 ng/mL to a maximum of 35.01 ng/mL for INVEGA TRINZA.
• After a slight initial increase, plasma levels were stabilized after the fourth administration of INVEGA SUSTENNA, and a slight reduction in plasma levels (not statistically significant) was observed during treatment with INVEGA TRINZA.
  • After steady-state paliperidone concentrations were achieved with INVEGA SUSTENNA treatment, the stability of plasma concentration of paliperidone was maintained during the transition to INVEGA TRINZA without oral supplementation of paliperidone.
• From the first study dose of INVEGA SUSTENNA to 9 months on treatment with INVEGA TRINZA, statistically significant improvements in Brief Psychiatric Rating Scale (BPRS) total scores (P=0.006), Positive and Negative Symptom Scale (PANSS) scores (P=0.0016), and Hamilton Rating Scale of Depression (HAM-D) scores (P=0.003) were observed.

Corbeil et al (2022)³ conducted a multicenter, retrospective, observational study to evaluate the effectiveness of INVEGA TRINZA among patients with schizophrenia who transitioned from INVEGA SUSTENNA to INVEGA TRINZA.

Study Design/Methods

• Patients aged ≥18 years with a diagnosis of schizophrenia spectrum psychotic disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification who received ≥1 dose of INVEGA TRINZA during observation period were included.
• The primary outcome measured was relapse, which was defined as an increase of psychotic symptoms requiring either:
  • Discontinuation of INVEGA TRINZA in favor of another antipsychotic
  • Increasing INVEGA TRINZA dose or reducing the dosing interval by >2 weeks
  • Use of supplemental oral antipsychotic due to psychotic symptoms
  • Psychiatric hospitalization

Results

• A total of 178 patients were included (mean age, 33.9 years) in the study.
  • In the 2 years prior to INVEGA TRINZA initiation, 50.6% of patients had been hospitalized at least once for psychiatric reasons, and the mean Clinical Global Impression – Severity (CGI-S) score was 3.1 at INVEGA TRINZA initiation.
• Patients received INVEGA SUSTENNA for an average of 2.4 years before being initiated on INVEGA TRINZA.
  • The last administered dose of INVEGA SUSTENNA was 156 mg and 234 mg in 35.6% and 35.1% of patients, respectively.
  • INVEGA TRINZA treatment was initiated at the doses of 546 mg and 819 mg in 36.5% and 39.9% of patients, respectively.
  • Majority of patients (90.8%) were transitioned from INVEGA SUSTENNA to INVEGA TRINZA at the conversion ratio of 3.5.
• At 12 months after transitioning to INVEGA TRINZA, 33 patients had a relapse, and 19 patients discontinued treatment with INVEGA TRINZA.
• At 12 months, the relapse-free survival probability was 0.788 (95% confidence interval [CI], 0.725-0.856), discontinuation-free survival probability was 0.863 (95% CI, 0.806-0.924), and hospitalization-free survival probability was 0.889 (95% CI, 0.840-0.940).
• The most common reasons for treatment discontinuation were side effects (n=7), insufficient response (n=4), patient’s decision (n=3), relapse (n=1), and other consideration (n=4).

Berwaerts et al (2015)⁴ conducted a DB, PBO-controlled, relapse-prevention study to evaluate the efficacy and safety of INVEGA TRINZA in delaying time-to-relapse of schizophrenia symptoms in patients previously treated with INVEGA SUSTENNA for at least 4 months. The study included 4 phases: a screening and oral tolerability testing phase of up to 3 weeks, a 17-week OL transition phase, a 12-week OL maintenance phase, and a DB phase of variable length.

• During the transition phase, all patients received 4 months of INVEGA SUSTENNA treatment.
• During the maintenance phase, patients received a single dose of INVEGA TRINZA (273, 410, 546, or 819 mg; a 3.5-fold multiple of the final INVEGA SUSTENNA dose administered) in either the deltoid or gluteal muscle.
• During the DB phase, stabilized patients were randomized 1:1 to receive a fixed dose of INVEGA TRINZA (the same dose as during the maintenance phase) or PBO.
• Table: Dosing Details for Patients Converting From Previous Antipsychotics in a Clinical Trial describes how patients converted to INVEGA TRINZA from their previous antipsychotic regimen.

CASE REPORT

Cellini et al (2021)⁶ evaluated variations in plasma concentrations and clinical outcomes and possible relapses in 5 clinically stable patients with schizophrenia or schizoaffective disorder who switched from INVEGA SUSTENNA to INVEGA TRINZA. Overall, 5 patients, including 4 with schizophrenia (age range, 42-83 years) and 1 with schizoaffective disorder (age, 51 years), were enrolled. No major comorbidities were present (except patient 4, who had type 2 diabetes mellitus), and no significant concomitant medications were administered (except diazepam ≤10 mg at bedtime or equivalent). All patients received INVEGA SUSTENNA for ≥9 months (except patient 1, who had received INVEGA SUSTENNA for 4 months), and all (except patients 3 and 5) were switched to a 3.5-fold dose of INVEGA TRINZA administered on day 0 and at months 3, 6, and 9. Paliperidone plasma levels, PANSS scores, and Global Assessment of Functioning (GAF) scores were monitored before each scheduled administration of INVEGA TRINZA.

In 3 patients, the baseline steady-state plasma concentration of paliperidone was within the therapeutic range (20-60 ng/mL) during INVEGA SUSTENNA maintenance. In patients 2, 4, and 5, the plasma concentrations were within the therapeutic range at baseline and reduced to subtherapeutic levels at month 3 after switching to INVEGA TRINZA. Patients 1 and 3 had subtherapeutic plasma concentrations of paliperidone at baseline, which remained stable throughout the follow-up period.

No relapse was reported throughout the follow-up period. In patients 2, 4, and 5, no strong relationship was established between the reduced plasma concentrations and clinical outcomes. The PANSS scores remained stable, and the GAF scores did not show significant worsening.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 03 January 2025.