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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

INVEGA SUSTENNA® (paliperidone palmitate)

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Adverse Event of INVEGA SUSTENNA- Cardiovascular Effects

Last Updated: 01/04/2025

Summary

BOXED WARNING: 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 SUSTENNA is not approved for use in patients with dementia-related psychosis.¹ Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.²
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.³
Orthostatic Hypotension and Syncope: Paliperidone palmitate can induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity. INVEGA SUSTENNA should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that predispose the patient to hypotension. Monitoring of orthostatic vital signs should be considered in patients who are vulnerable to hypotension.³
Clinical Studies: Cardiovascular adverse events have been reported in clinical studies of INVEGA SUSTENNA. See Table: Clinical Trial Data.

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 25, 50, 75, 100, and 150 mg eq. are equal to 39, 78, 117, 156, and 234 mg of paliperidone palmitate, respectively.

CLINICAL STUDIES

Clinical Trial Data

Trial Design	Cardiovascular Effects
SCHIZOPHRENIA
DOUBLE-BLIND CLINICAL TRIALS
Pandina (2011)⁴ conducted a 13-week, randomized, DB, double-dummy, active-controlled, parallel-group, multicenter study assessing non-inferiority of INVEGA SUSTENNA to risperidone long-acting injection (RLAI) in the treatment of patients with schizophrenia (n=1,214, safety analysis set). INVEGA SUSTENNA (n=606): Deltoid injection of INVEGA SUSTENNA 234 mg on day 1 followed by a 156-mg deltoid injection on day 8; thereafter, patients received flexibly dosed INVEGA SUSTENNA injections on days 36 (78 or 156 mg) and 64 (78, 156, or 234 mg) in either the deltoid or gluteal muscle. RLAI (n=608): RLAI 25 mg on days 8 and 22, followed by 25 or 37.5 mg on days 36 and 50; thereafter, patients received flexible doses of 25, 37.5, or 50 mg on days 64 and 78, all in the gluteal muscle. Oral supplementation with RIS (1-6 mg) was administered for the first 28 days. -Optional supplementation with RIS was permitted under certain circumstances outlined in the protocol.	Reports of cardiac arrhythmias, QT interval, ischemia, and cardiovascular events were low and comparable in both the INVEGA SUSTENNA and RLAI treatment groups. No clinically relevant vital sign or ECG changes were observed in either the INVEGA SUSTENNA or RLAI treatment groups. One death was reported in the RLAI-treatment group due to pulmonary embolism after study completion.
Hough (2010)⁵, Gopal (2010a)⁶ conducted a longer-term, DB, randomized, multicenter, PBO-controlled, parallel group study examining the efficacy and safety of INVEGA SUSTENNA in delaying time-to-relapse in schizophrenic patients following an initial 9-week, OL transition phase and 24-week, OL maintenance phase (n=849, transition and maintenance population; n=408, DB safety analysis set). Dosing Schedule (All doses administered IM via gluteal muscle): 9-week OL transition phase: INVEGA SUSTENNA 78 mg on day 1 and day 8 followed by adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the rest of the transition period. 24-week OL maintenance phase: Adjustable INVEGA SUSTENNA doses (39, 78, or 156 mg) administered every 4 weeks for the first 12 weeks followed by fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg. every 4 weeks for the last 12 weeks. DB phase: Fixed INVEGA SUSTENNA doses of 39, 78, or 156 mg (n=205) or PBO (n=203) every 4 weeks.	Tachycardia was reported by 9 (1%) patients and sinus tachycardia by one patient during the transition/maintenance phase. One patient discontinued the study due to tachycardia. During the DB phase, one patient receiving PBO discontinued treatment due to a myocardial infarction. One patient, who experienced ventricular extrasystoles in the maintenance phase, discontinued treatment during the DB phase. One patient died due to a heart attack 10 days after discontinuing the study due to a suicide attempt. QTcLD shifts from a normal predose value to a prolonged maximum value occurred in 1 patient during the transition/maintenance period and in 1 patient receiving INVEGA SUSTENNA during the DB period. QTcLD shifts from a normal predose value to a borderline maximum value occurred in 24 patients during the transition/maintenance period, and in 7 patients receiving INVEGA SUSTENNA during the DB period. Two patients had QTcLD values >480 msec during the transition/maintenance period.
Gopal (2010)⁷ conducted a 13-week, multicenter, randomized, DB, PBO-controlled, dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (78, 156, or 234 mg), administered via gluteal injection on days 1, 8, 36 and 64, in patients with schizophrenia (n=388, safety analysis set).	Increased blood pressure occurred ≥3% more frequently in patients who received INVEGA SUSTENNA 78 mg or 156 mg than in those who received PBO. Tachycardia, sinus tachycardia, and tachyarrhythmia each occurred in 2 patients receiving INVEGA SUSTENNA and 2 patients receiving PBO. None of the patients receiving INVEGA SUSTENNA had corrected QTcLD intervals of >480 msec.
Kramer (2010)⁸ conducted a 9-week, DB, randomized, international study comparing the safety and efficacy between INVEGA SUSTENNA (two fixed doses) and PBO in the treatment of adults with schizophrenia (n=247). Following a 5-day screening/washout phase and a 7-day oral run-in period, patients were randomized to receive gluteal IM injections of INVEGA SUSTENNA 78 mg (n=79), INVEGA SUSTENNA 156 mg (n=84), or PBO (n=84), without oral supplementation, on days 1, 8, and 36.	Compared to PBO, INVEGA SUSTENNA groups experienced higher rates of treatment-emergent orthostatic hypotension (4% versus 6-11%, respectively). Three patients in the INVEGA SUSTENNA 156 mg group and one patient in the PBO group experienced tachycardia. One INVEGA SUSTENNA patient experienced an episode of syncope. None of the patients receiving INVEGA SUSTENNA had corrected QTc intervals of >500 msec. Abnormally high heart rate (≥100 bpm) was reported by 17 patients in the INVEGA SUSTENNA 78 mg group, 10 patients in the INVEGA SUSTENNA 156 mg group, and 6 patients in the PBO group. Abnormally low heart rate (≤50 bpm) was reported by 5 patients in the INVEGA SUSTENNA 78 mg group, 4 patients in the INVEGA SUSTENNA 156 mg group, and 4 patients in the PBO group.
Nasrallah (2010)⁹ conducted a 13-week, phase 3, multicenter, randomized, DB, PBO-controlled, parallel group, international dose-response study evaluating the efficacy and safety of 3 fixed doses of INVEGA SUSTENNA (39, 78, or 156 mg), administered by gluteal IM injection on days 1, 8, 36, and 64, in patients with schizophrenia (n=517, safety analysis set).	Tachycardia or sinus tachycardia occurred in 2 patients, one who received INVEGA SUSTENNA 39 mg and one who received INVEGA SUSTENNA 156 mg. No increased cardiovascular risk was reported for patients treated with INVEGA SUSTENNA for doses up to 156 mg. None of the patients receiving INVEGA SUSTENNA had corrected QTcLD intervals of >480 msec.
Pandina (2010)¹⁰; Haskins (2009)¹¹ 13-week, phase 3, randomized, DB, PBO-controlled, international dose response INVEGA SUSTENNA study conducted in patients experiencing an acute exacerbation of established schizophrenia (n=652). Initiation Dose: Day 1 (Deltoid IM inj) INVEGA SUSTENNA 234 mg (n=488) PBO (n=164) Fixed Dose: Day 8, 36, and 64 (Deltoid or Gluteal IM inj) INVEGA SUSTENNA 234 mg (n=163) INVEGA SUSTENNA 156 mg (n=165) INVEGA SUSTENNA 39 mg (n=160) PBO (n=164)	Pulse rates ≥100 bpm and increases of ≥15 bpm were observed in 6%-11% of INVEGA SUSTENNA patients when measurements were taken with the patient in standing position and in 2%-5% of patients when taken in the supine position. No clinically significant QTc prolongation was observed with doses of INVEGA SUSTENNA up to 234 mg. No subject had a QTcLD value of >480 msec or a maximum change of >60 msec during the study. Post Hoc Analysis: An additional post hoc analysis of the Pandina (2010) trial assessed the following outcome: recent diagnosis¹²
Hough (2009)¹³ conducted a 25-week, randomized, DB, multicenter, cross-over study assessing the safety and tolerability of INVEGA SUSTENNA administered via a deltoid or gluteal IM injection in adults with stable schizophrenia (n=252, safety analysis set). Patients were randomized to receive one of two injection-site sequences (Period 1: Doses administered on days 1, 8, 36, and 64 followed by Period 2: Doses administered on days 92, 120, and 148). GD (Gluteal IM inj during period 1 followed by Deltoid IM inj during period DG (Deltoid IM inj during period 1 followed by Gluteal IM inj during period 2)	In period 1, the incidence of tachycardia was 5% in the GD group and <5% in the DG group; in period 2, the incidence of tachycardia was 5% in both the GD and DG groups. The incidence of sinus tachycardia and bundle branch block was reported in at least 5% of patients in any dose group.
ADDITIONAL DOUBLE-BLIND TRIALS
Weiden (2020)¹⁴ conducted a 26-week, phase 3b DB trial to evaluate the safety and efficacy of a 2-month formulation of AL in patients hospitalized for acute exacerbation of schizophrenia followed by transition to outpatient care (ALPINE). INVEGA SUSTENNA was included as an active control, but the study was not powered for direct comparisons between the randomized groups. AL (n=99)¹⁴: AL Nano Crystal Dispersion plus a single 30 mg dose of oral aripiprazole on day 1 followed by AL 1064 mg IM gluteal on day 8 and every 8 weeks. INVEGA SUSTENNA (n=101)¹⁴: 234 mg deltoid injection on day 1 and 156 mg deltoid injection on day 8 followed by 156 mg IM gluteal every 4 weeks. The study did not allow for flexible INVEGA SUSTENNA dosing. Citrome et al (2024)¹⁵ conducted a post hoc analysis of the ALPINE study to evaluate the safety and tolerability of AL and INVEGA SUSTENNA.	In the post hoc analysis of the ALPINE study, in the INVEGA SUSTENNA group¹⁵: 4 (4.0%) patients reported hypotension AEs (mild to moderate in severity) 1 patient discontinued treatment due to dizziness 22 (21.8%) patients received concomitant hypertension medications, but none reported AEs related to hypotension
Savitz et al (2016)¹⁶ conducted a randomized, DB, parallel-group, multicenter, noninferiority study of paliperidone palmitate 3-month (PP3M) and INVEGA SUSTENNA. During the OL stabilization phase, 1,429 patients received INVEGA SUSTENNA in the following doses: Initiation doses, IM deltoid (234 mg on day 1; 156 mg on day 8); Weeks 5 and 9: flexible dosing between 78-234 mg (deltoid or gluteal administration). The week 13 dose was the same as week 9 Based on pre-defined criteria, patients who were clinically stable after completing the OL phase were randomized (1:1) into the 48-week, DB phase. Patients received fixed doses of INVEGA SUSTENNA every 4 weeks (78, 117, 156 or 234 mg; n=512) or PP3M every 3 months (273, 410, 546, 819 mg; n=504) in the deltoid or gluteal muscle.	The mean duration of exposure was 295.1 days for PP3M at a mean dose of 647.01 mg and 286.7 days for INVEGA SUSTENNA at a mean dose of 185.8 mg. The incidence of TEAEs related to tachycardia, orthostatic hypotension, and QT prolongation was comparable between the PP3M and INVEGA SUSTENNA groups. During the DB phase, 1 patient in the INVEGA SUSTENNA group (and none in the PP3M group) experienced a shift in QTc interval from normal average predose value to maximum interval value ≥500 msec based on QTcB, QTcF, QTLc, and QTcLD. A maximum increase of >30 to 60 msec from the average predose value, based on QTcLD, was observed in 10% and 6% of PP3M and INVEGA SUSTENNA patients, respectively. In addition, 1 patient each in the PP3M and INVEGA SUSTENNA groups had a maximum increase of >60 msec from the average predose value. Minimal changes in vital signs occurred and were similar in both treatment groups. During the OL phase, one patient died following cardiac arrest.
Takahashi et al (2013)¹⁷ conducted a 13-week, randomized, DB, PBO-controlled trial assessing the safety and efficacy of INVEGA SUSTENNA in Asian patients with schizophrenia (N=323; mean age: 45 years; 57% male). INVEGA SUSTENNA (n=159): 234 mg on day 1 (deltoid IM); 156 mg on day 8 (deltoid IM); once-monthly injections of 117 mg (deltoid IM or gluteal IM) on days 36 and 64. PBO (n=164)	Mean duration of INVEGA SUSTENNA and PBO exposure was 87 and 50 days, respectively. During the study, one death occurred (PBO group, primary cause cardiac failure). QT prolongation was reported in one patient from each treatment group.
OPEN-LABEL CLINICAL TRIALS
Si et al (2015)¹⁸ conducted a 13-week, OL, single-arm, multicenter prospective study examining the efficacy and safety of INVEGA SUSTENNA in Chinese patients with acute schizophrenia (safety analysis set: n=616). Dosing: Deltoid IM injection on day 1 (234 mg) and day 8 (156 mg) followed by flexible once-monthly injections of 117-234 mg (deltoid IM or gluteal IM) administered on days 36, 64 and 92. Stable doses of antidepressants were permitted if started 30 days before study.	Mean INVEGA SUSTENNA dose: 179 mg Mean duration of exposure: 94 days Treatment discontinuation due to TEAEs occurred in 17 patients (2.8%) and included bradycardia and sinus bradycardia (1 case each). At baseline, 170 patients (27.6%) had ECG abnormalities versus 83 patients (13.5%) at endpoint (13 weeks).
Zhang et al (2015)¹⁹ conducted a phase 3b, OL, multicenter study evaluating the safety, tolerability, and efficacy of INVEGA SUSTENNA in Asian/Australian patients with recent-onset schizophrenia who previously failed treatment with oral antipsychotics (n=521 ITT/safety population). Dosing: Deltoid IM injection on day 1 (234 mg) and day 8 (156 mg) followed by flexible once-monthly injections of 78-234 mg (deltoid IM or gluteal IM).	Mean duration of exposure: 382.6 days Mean maintenance dose: 157.2 mg Observed cardiac AEs included: palpitations or sinus arrhythmia (0.8% each), sinus bradycardia, hypertension or orthostatic hypotension (0.4% each) and increased blood pressure (0.2%).
Cleton (2014)²⁰ conducted an international, multicenter, single-dose, randomized, OL, parallel-group study evaluating the dose proportionality of INVEGA SUSTENNA injections administered via the gluteal or deltoid muscle in patients with clinically stable schizophrenia (n=201). Dosing: Randomization to a single OL dose of INVEGA SUSTENNA (39, 78, 156, or 234 mg IM injection into the deltoid or gluteal muscle)-Patients were followed for a period of ≤126 days after the single injection. Concomitant use of pre-existing oral antipsychotic medications (except paliperidone ER, risperidone, clozapine, thioridazine or ziprasidone), adjusted to the lowest clinically effective dose, were permitted during the trial.	One of the most common TEAEs included tachycardia (n=20). Twenty patients (10 deltoid; 10 gluteal) experienced treatment-emergent orthostatic hypotension (sustained decrease in SBP >20mm Hg or DBP >10mm Hg upon standing for ≥2 minutes, associated with an increase in pulse >15 bpm) with neither injection group experiencing a dose-dependent increase in incidence. Concomitant use of oral antipsychotics may have influenced the occurrence of orthostatic hypotension. No patients experienced a QTcLD interval >500 msec. Maximum postbaseline QTc intervals ranged from 431-452 msec (deltoid) and 418-471 msec (gluteal).
Rossenu (2014)²¹ conducted a randomized, single-center, multiple-dose, OL, parallel-group study assessing the pharmacokinetics of INVEGA SUSTENNA at steady state following multiple *deltoid or gluteal* IM injections in patients with stable schizophrenia (n=49). Dosing Schedule: ≤21-day screening period -OL treatment phase of INVEGA SUSTENNA 156 mg administered via the *deltoid* (n=24) or *gluteal* (n=25) muscle on days 1, 8, 36, and 64.	TEAEs Reported by ≥10% of Patients Included: Orthostatic Hypotension Deltoid: 33%; Gluteal: 16% Hypotension Deltoid: 8% (n=2/24); Gluteal: 20% Diastolic Hypertension Deltoid: 13% (n=3/24); Gluteal: 12% Hypertension Deltoid: 4% (n=1/24); Gluteal: 12% ECGs and Vitals No QTcLD (population-specific linear-derived) levels >450 msec were observed at any post-baseline assessment point. Orthostatic hypotension (as defined by Cleton et al, 2014²⁰) was observed in 42% (n=10) and 32% (n=8) of patients in the deltoid and gluteal groups, respectively. During the study, 23 patients (47%) experienced an abnormally high supine pulse rate (increase by ≥15 bpm from baseline to at least 100 bpm) at least once during the study, with no between group differences.
Wakamatsu et al (2013)²² conducted a 57-week, OL, flexible-dose study evaluating the long-term safety and efficacy of INVEGA SUSTENNA in Japanese patients with schizophrenia (N=201; mean age: 45.5 years; 51.7% male; n=184 in safety analysis set). Dosing: Deltoid IM injection on day 1 (234 mg) and day 8 (156 mg) followed by flexible once-monthly injections (deltoid IM or gluteal IM).	Mean INVEGA SUSTENNA dose: 166.8 mg Mean duration: 238.7 days Cardiac disorders following treatment were low (≤2.5%). No additional detail was provided.
Coppola (2012)²³ conducted a 53-week, OL, multidose, multicenter study evaluating the pharmacokinetics and long-term safety and tolerability of INVEGA SUSTENNA 234 mg in adults with stable schizophrenia (n=212, safety analysis set). Following a screening and washout phase of ≤21 days, each patient received a deltoid IM injection of INVEGA SUSTENNA 234 mg on day 1. Each patient who tolerated the dose (Group A, n=186) received a second deltoid IM injection of INVEGA SUSTENNA 234 mg on day 8 and 12 once-monthly injections (deltoid or gluteal muscle) starting on day 36. Patients who were unable to tolerate the 234-mg dose or unwilling to participate in intensive pharmacokinetic sampling (Group B, n=26) received a second IM injection of INVEGA SUSTENNA 78-234 mg (flexible dose) on day 8 (deltoid or gluteal muscle) and 12 once-monthly injections starting on day 36 (deltoid or gluteal muscle).	Twenty-seven patients reported tachycardia, leading to discontinuation in 1 patient. Two patients reported syncope, leading to discontinuation in 1 patient. Eighteen patients spontaneously reported orthostatic hypotension (mild in severity), and 22% of patients had orthostatic changes in blood pressure. Eleven patients reported hypertension. No incidence of QTc interval prolongation >500 msec was reported. One patient reported bradycardia.
Li (2011)²⁴ conducted a 13-week, OL, phase 3, randomized, active-controlled, parallel-group, multicenter, rater-blinded, comparative study to demonstrate the noninferiority of INVEGA SUSTENNA to RLAI in adult Chinese patients with acute schizophrenia (safety analysis set, n=452). INVEGA SUSTENNA (n=229): Deltoid IM injection on day 1 (234 mg) and day 8 (156 mg) with the optional injection site of the gluteal muscle for days 36 (78 or 156 mg) and 64 (78-234 mg). RLAI (n=223): Gluteal IM injection on days 8 and 22 (25 mg); flexible doses of 25 or 37.5 mg on days 36 and 50; and flexible doses of 25-50 mg every 2 weeks thereafter beginning on day 64. -Daily oral RIS supplementation occurred during the first 4 weeks (2 mg on day 1 and flexible doses of 1-6 mg on days 2 through 28). Additional oral RIS 1-2 mg was allowed during the 3-week period after each dosage increase.	Tachycardia was reported by 4 (<2%) patients in each treatment group. One TEAE of mild orthostatic hypotension was reported in one INVEGA SUSTENNA-treated patient on day 64. None of the patients showed clinically noteworthy changes in QTc intervals from baseline to endpoint.
META-ANALYSES
Gopal (2011)²⁵ conducted a meta-analysis of 64 randomized, DB, PBO- or active-controlled clinical trials evaluating the occurrence of cardiac TEAEs and effect on QT interval; cumulative review of post-marketing safety data Three groups were analyzed: RIS or PALI (oral or LAI, any dose) PBO active control	Most results were reported as pooled data for RIS and PALI; oral forms were studied in 56/64 trials. Results specific to PALI are as follows: Change from baseline in maximum QTcF in PBO-controlled trials (PBO, n=1,412; PALI, n=3,327): <30 msec: PBO, 93.8%; PALI, 93.7% 30–60 msec: PBO, 6.1%; PALI, 6.1% >60 msec: PBO, 0.1%; PALI, 0.2% Post-marketing experience with PALI: 6 fatal outcomes related to torsade de pointes/QT prolongation: sudden cardiac death (n=2), cardiac arrest (n=2), sudden death (n=1), torsade de pointes (n=1) There was insufficient evidence to support a causal association between PALI and sudden death.
SCHIZOAFFECTIVE DISORDER
Fu et al (2015)²⁶ conducted an international, long-term, DB, PBO-controlled, randomized-withdrawal study of INVEGA SUSTENNA in patients with schizoaffective disorder. During the 15-month, DB phase, stable patients were randomized to PBO (n=170) or a fixed dose of INVEGA SUSTENNA (n=164) The INVEGA SUSTENNA dose distribution during the DB phase: 78 mg (4.9%), 117 mg (9.8%), 156 mg (47%) or 234 mg (38.4%) doses.	DB: Twelve INVEGA SUSTENNA patients discontinued treatment due to TEAEs which included congestive cardiac failure.
Abbreviations: AE, adverse event; AL, aripiprazole lauroxil; bpm, beats per minutes; DB, double-blind; DBP, diastolic blood pressure; ECG, electrocardiogram; IM, intramuscular; LAI, long-acting injection; ITT, intent-to-treat; OL, open-label; PALI, paliperidone; PBO, placebo; RIS, risperidone; RLAI, risperidone long-acting injection; SBP, systolic blood pressure; TEAE, treatment emergent adverse event; QTcB, QT corrected for heart rate using Bazett's formula; QTcF, QT corrected for heart rate using Fridericia's formula; QTcLD, QT linear-derived correction; QTLc, QT, linear corrected. ^aPeriod 1: doses administered on days 1, 8, 36, and 64; period 2: doses administered on days 92, 120, and 148.

Real-world Study

Shen et al (2024)²⁷ conducted a real-world, retrospective, longitudinal cohort study using Taiwan’s National Health Insurance Research Database from March 2012 to December 2018 to evaluate the incidence rate and risk of cardiovascular events in patients with schizophrenia or schizoaffective disorder, who were treated with ≥1 second-generation antipsychotics (SGAs), following treatment with INVEGA SUSTENNA (primary cohort) vs oral SGAs (comparator cohort).

The study included 11,023 patients with a mean (standard deviation [SD]) age of 43.2 (12.2) years; 50.5% were male.
During a mean (SD) follow-up of 1.04 (1.22) years:
- Serious cardiovascular events, including severe ventricular arrhythmias (SVAs), cardiac arrest, and sudden death, were reported in 45 patients on INVEGA SUSTENNA, with an overall incidence rate of 3.92 (95% confidence interval [CI], 2.86-5.25) per 1000 patient-years.
- Expanded serious cardiovascular events, including SVAs, cardiac arrest, sudden death, acute myocardial infarction, and ischemic stroke, were reported in 90 patients on INVEGA SUSTENNA, with an overall incidence rate of 7.88 (95% CI, 6.33-9.68) per 1000 patient-years.
- Cardiovascular hospitalizations were reported in 571 patients on INVEGA SUSTENNA, with an overall incidence rate of 51.96 (95% CI, 47.78-56.40) per 1000 patient-years.
In the comparative cardiovascular risk analysis, 92% (n=10,115) of the primary INVEGA SUSTENNA cohort was matched at 1:1 with the comparator oral SGA cohort.
During the mean (SD) follow-up of 1.05 (1.24) and 0.74 (1.10) years for the primary and comparator cohorts, respectively:
- Serious cardiovascular events were reported in 40 patients on INVEGA SUSTENNA vs 35 patients on oral SGAs (overall incidence rate: INVEGA SUSTENNA, 3.76 [95% CI, 2.68-5.12] per 1000 patient-years; oral SGAs, 4.70 [95% CI, 3.28-6.54] per 1000 patient-years).
- Expanded serious cardiovascular events were reported in 81 patients on INVEGA SUSTENNA vs 69 patients on oral SGAs (overall incidence rate: INVEGA SUSTENNA, 7.64 [95% CI, 6.07-9.49] per 1000 patient-years; oral SGAs, 9.31 [95% CI, 7.24-11.78] per 1000 patient-years).
- Cardiovascular hospitalizations were reported in 488 patients on INVEGA SUSTENNA vs 483 patients on oral SGAs (overall incidence rate: INVEGA SUSTENNA, 47.73 [95% CI, 43.59-52.16] per 1000 patient-years; oral SGAs, 68.43 [95% CI, 62.46-74.81] per 1000 patient-years).
The treatment groups had no significant differences in the risks of serious and expanded cardiovascular events.
The INVEGA SUSTENNA group accounted for 22% of decreased risk of cardiovascular hospitalizations compared with the oral SGA group (hazard ratio, 0.78; 95% CI, 0.69-0.89; P=0.0002).

Cicala et al (2023)²⁸ conducted a real-world, retrospective study analyzing Individual Case Safety Report (ICSR) data from the EUDRAVigilance database between 2011 and 2022 for the use of INVEGA SUSTENNA and INVEGA TRINZA.

A total of 8,152 ICSRs for INVEGA SUSTENNA and INVEGA TRINZA were reported out of 20,226 second generation antipsychotic long-acting injectable cases examined. The frequency of cardiac disorders reported as adverse drug reactions in ICSRs was 5.1% (n/N=320/6,332) for INVEGA SUSTENNA.

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 05 December 2024.

References

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