Summary

• 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. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature.¹
• QT Prolongation: INVEGA TRINZA causes a modest increase in the corrected QT (QTc) interval. The use of paliperidone should be avoided in combination with other drugs that are known to prolong the QTc interval. Paliperidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.²
• Orthostatic Hypotension and Syncope: Paliperidone can induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. INVEGA TRINZA should be used with caution in patients with known cardiovascular disease (eg, heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (eg, dehydration, hypovolemia, and treatment with antihypertensive medications). Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension.²
• Tachycardia has been observed in the long-term maintenance trial for INVEGA TRINZA.³
• An observational study in 31 patients with schizophrenia reported that INVEGA TRINZA did not significantly differ from INVEGA SUSTENNA in Qrisk3 values, a cardiovascular risk index, but showed a significant difference in 10-year risk scores due to age variations.⁴ 

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate can 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., 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., respectively.

CLINICAL STUDIES

Berwaerts et al (2015)³ conducted a double-blind (DB), placebo (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 open-label (OL) transition phase, a 12-week OL maintenance phase, and a DB phase of variable length. During the transition phase, all patients except those who were receiving other long-acting injectable (LAI) antipsychotics or those who were receiving INVEGA SUSTENNA before entering the study received 4 months of INVEGA SUSTENNA treatment. Dosing included the following: day 1: INVEGA SUSTENNA 234 mg (deltoid intramuscular [IM] administration); day 8: INVEGA SUSTENNA 156 mg (deltoid IM administration); days 36 and 64: INVEGA SUSTENNA 78, 117, 156, or 234 mg flexible doses (deltoid IM or gluteal IM administration); and day 92: the same dose of INVEGA SUSTENNA as was administered on day 64. 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 on day 92) 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. In addition to efficacy, safety and laboratory parameters were measured.

Syncope was reported in <1% (1/506) of patients who received INVEGA SUSTENNA during the OL phase. There were no cases of syncope reported during the DB phase in either treatment group. Orthostatic hypotension was reported in <1% (1/506) of patients who received INVEGA SUSTENNA and <1% (1/379) of patients after receiving a single dose of INVEGA TRINZA during the OL phase. There were no cases of orthostatic hypotension reported during the DB phase in either treatment group.⁵

A higher percentage of PBO- vs INVEGA TRINZA-treated patients experienced treatment-emergent abnormally high heart rate (≥100 beats per minute [bpm]) relative to average predose value (10 of 145 [7%] vs 3 of 160 [2%]). Similar percentages of PBO- vs INVEGA TRINZA-treated patients experienced treatment-emergent abnormally low heart rate (≤50 bpm; 4 of 145 [3%] vs 4 of 160 [3%]) and abnormally high PR duration (≥210 msec; 3 of 145 [2%] vs 2 of 160 [1%]) relative to average predose value. QTc interval change from DB baseline to maximum corrected QT interval is listed in Table: QTc Change from DB Baseline to Maximum Corrected QT Interval.³

Observational Study

Ispir et al (2024)⁴ studied 31 patients with schizophrenia (mean age, 44.4 years; female, 48.4%) and reported mean Qrisk3 values (a cardiovascular risk index) in patients taking INVEGA SUSTENNA or INVEGA TRINZA. INVEGA TRINZA did not significantly differ from INVEGA SUSTENNA in Qrisk3 values, but a significant difference in 10-year risk score (INVEGA SUSTENNA, 3.7±4.2; INVEGA TRINZA, 4.6±4.8, P=0.003) was attributed to variations in age.

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 13 January 2025.