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 HAFYERA 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: Paliperidone palmitate 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.^2,3
• Orthostatic Hypotension and Syncope: Paliperidone palmitate can induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. INVEGA HAFYERA 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
• During the double-blind (DB) phase of the INVEGA HAFYERA randomized, DB, active controlled study in patients with schizophrenia, QTcLD (QT interval corrected for heart rate using the population specified linear derived method) exceeding 60 msec was observed in 2 patients (0.4%) in the INVEGA HAFYERA treatment group and in 2 patients (0.9%) in the INVEGA TRINZA treatment group. No patients had a QTcLD value of >480 msec at any point in the study.³

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate can be expressed in mg eq. of paliperidone (active moiety) or mg 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.
• INVEGA HAFYERA doses expressed as 1,092 or 1,560 mg of paliperidone palmitate are equal to 700 and 1,000 mg eq of paliperidone, respectively.

CLINICAL DATA

Noninferiority Trial⁴

A phase 3, randomized, DB, active-controlled, parallel-group, multicenter, non-inferiority trial was conducted to evaluate the efficacy and safety of INVEGA HAFYERA relative to INVEGA TRINZA on time to first relapse in adults with schizophrenia who were previously stabilized on corresponding doses of INVEGA SUSTENNA or INVEGA TRINZA. See FIGURE: Study Design

Results

Orthostatic hypotension was reported in 0.4% (2/478) of patients in the INVEGA HAFYERA group and 0.9% (2/224) of patients in the INVEGA TRINZA group during the DB phase.⁴

During the DB phase, tachycardia-related treatment-emergent adverse events (TEAEs) were observed in 1.5% (7/478) and 0.4% (1/224) of patients in the INVEGA HAFYERA and INVEGA TRINZA groups, respectively. Bradycardia was reported in 0.2% (1/478) and 0.9% (2/224) of patients in the in the INVEGA HAFYERA and INVEGA TRINZA groups, respectively.⁵

One patient (0.4%) in the INVEGA HAFYERA group during the DB phase had a TEAE of myocardial ischemia that was not deemed serious by the investigator and did not lead to study discontinuation.⁴

During the DB Phase, QTcLD exceeding 60 msec was observed in 0.4% (2/474) of patients in the INVEGA HAFYERA treatment group and in 0.9% (2/220) in the INVEGA TRINZA group relative to the value at DB baseline. All reported events related to QT prolongation in the DB phase were non-serious and did not result in study drug discontinuation. No patient had a QTcLD value of >480 msec at any point in the study.^3,6

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 During DB Phase.

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 11 June 2024.