Medical inquiries

Connect with my medical science liaison

Chat live

Available Monday - Friday 9AM - 4:30PM ET

Call me now

Available Monday - Friday 9AM - 7:30PM ET

Email your inquiry

Call 1-800-526-7736

Available Monday - Friday 9AM - 8PM ET

Live video

Available Monday - Friday 9AM - 4:30PM ET

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)

Medical Information

+ Save link

Dosing of INVEGA SUSTENNA – Maximum Dose

Last Updated: 09/17/2024

Summary

The maximum monthly dose of INVEGA SUSTENNA is 234 mg. Monthly doses of INVEGA SUSTENNA higher than 234 mg have not been systematically evaluated.¹
A 1-year, open-label, multiple-dose study assessed the safety and tolerability of the 234-mg dose of INVEGA SUSTENNA, administered on day 1, day 8, and once monthly, in patients with schizophrenia. The study illustrated that patients receiving 234 mg INVEGA SUSTENNA remained symptomatically and functionally stable during the study and no new safety signals were identified.²
A 13-week, randomized, double-blind, placebo-controlled trial for the treatment of schizophrenia was conducted with INVEGA SUSTENNA initiated at 234 mg in the deltoid muscle, followed by fixed-dose injections (39, 156, or 234 mg) into either the gluteal or deltoid muscle one week later, and then continued once monthly. INVEGA SUSTENNA significantly improved mean total Positive and Negative Syndrome Scale (PANSS) scores from baseline to endpoint vs. placebo in all groups (P≤0.034). The safety profile of all three doses of INVEGA SUSTENNA was found to be similar to that of placebo.³^,⁴
Pharmacokinetic (PK) simulations with INVEGA SUSTENNA deltoid injections were conducted to evaluate the steady state plasma concentration profiles of the highest recommended maintenance dose (234 mg every 4 weeks) compared to two higher than recommended or more frequently administered regimens (two 156 mg injections every 4 weeks or 234 mg every 3 weeks). The two higher/more frequent dosing regimens produced higher plasma concentrations than the recommended highest maintenance dose regimen of 234 mg every 4 weeks. Simulated plasma concentration profiles of the dosing regimens indicated that steady state peak paliperidone levels with two 156 mg injections every 4 weeks were higher than 234 mg every 3 weeks.⁵
A 3-year, prospective, observational, open-label, non-randomized study in Spain evaluated adherence, long-term tolerability, and effectiveness of high INVEGA SUSTENNA doses in 30 patients with severe schizophrenia.⁶ The average INVEGA SUSTENNA dose was 356.8 mg/28 days (range: 273 mg to 624 mg/28 days). A significant improvement was observed in clinical severity as determined by the Clinical Global Impression-Severity (CGI-S) scale score. Forty percent of patients reported at least one mild adverse event with somnolence, EPS, and injection site pain most commonly reported.

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., respectively.

pUBLISHED lITERATURE

CLINICAL TRIAL DATA

Lead Author/Trial Design	Results
DOUBLE-BLIND CLINICAL TRIALS
Pandina (2010)³; Haskins (2009)⁴ conducted a 13-week, phase 3, randomized, double-blind, placebo-controlled, international dose-response INVEGA SUSTENNA study conducted in patients experiencing acute exacerbations of established schizophrenia (n=652). Following a ≤7-day screening, washout, and tolerability period, patients were randomized to one of three INVEGA SUSTENNA treatment arms or PBO: *Initiation Dose* Day 1 (Deltoid IM Inj) INVEGA SUSTENNA 234 mg (n=488) PBO (n=164) *Fixed Dose* Days 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)	*Efficacy:* Change in mean PANSS total score: INVEGA SUSTENNA 39 mg: -8.0 (P<0.034 vs PBO) INVEGA SUSTENNA 156 mg: -11.6 (P<0.001 vs PBO) INVEGA SUSTENNA 234 mg: -13.2 (P<0.001 vs PBO) PBO: -2.9 Mean change (baseline to endpoint) in PSP score, PANSS factor scores, PANSS subscales, and median change in CGI-S scores were all significantly different (P<0.05) between the INVEGA SUSTENNA 156- and 234-mg groups and the PBO group *Safety:* TEAEs occurred at similar rates between the INVEGA SUSTENNA (60% to 63%) and PBO groups (65%) Serious TEAEs: INVEGA SUSTENNA 39 mg: 9.4% INVEGA SUSTENNA 156 mg: 13.3% INVEGA SUSTENNA 234 mg: 8.0% PBO: 14% TEAEs occurring more frequently with INVEGA SUSTENNA than with PBO: injection-site pain (INVEGA SUSTENNA, 7.6% vs PBO, 3.7%) dizziness (INVEGA SUSTENNA, 2.5% vs PBO, 1.2%) sedation (INVEGA SUSTENNA, 2.3% vs PBO, 0.6%) extremity pain (INVEGA SUSTENNA, 1.6% vs PBO, 0%) myalgia (INVEGA SUSTENNA, 1% vs PBO, 0%) Most common EPS-related AE was akathisia (<6% of patients across all treatment groups) Prolactin-related TEAEs: ejaculation disorder (PBO, n=1; INVEGA SUSTENNA 39 mg, n=1) loss of libido (INVEGA SUSTENNA 156 mg, n=1) galactorrhea (INVEGA SUSTENNA 234 mg, n=1) Weight increase (≥7%) was dose related: INVEGA SUSTENNA 39 mg: 6% INVEGA SUSTENNA 156 mg: 8% INVEGA SUSTENNA 234 mg: 13% PBO: 5% No clinically meaningful changes in ECGs, vital signs, or other laboratory parameters
OPEN-LABEL CLINICAL TRIALS
Fernández-Miranda and Diaz-Fernández (2016)⁶ conducted A 3-year, prospective, observational, open-label, non-randomized study of patients with severe schizophrenia to evaluate adherence, long-term tolerability, and effectiveness of anti-psychotic treatment with high doses (≥273mg/28 days) of INVEGA SUSTENNA in standard clinical practice in Spain. Patients (≥18 years old) likely to benefit from INVEGA SUSTENNA due to risk of medication noncompliance, lack of effectiveness, or unacceptable adverse events (AEs) with previous antipsychotic treatments were included in the study. INVEGA SUSTENNA was initiated at doses of 234 mg on day 1 and 156 mg on day 7 via the deltoid muscle followed by flexible doses administered every 28 days (deltoid or gluteal). Concomitant use of antidepressants, mood stabilizers, antiparkinsonian agents, and benzodiazepines were permitted if patients were on stable doses for ≥30 days prior to initiating INVEGA SUSTENNA. Treatment discontinuation occurred if patients developed new-onset diabetes mellitus, weight gain ≥7 kg, tardive dyskinesia, clinical worsening determined by CGI-S measures, or any serious AEs. Following 3 months of treatment, patients experiencing a lack of clinical effectiveness (CGI-S ≥5 following treatment with INVEGA SUSTENNA at doses ≤234 mg) with no observed side effects were treated with INVEGA SUSTENNA doses over 234 mg/28 days to achieve clinical stabilization. In addition, higher doses were also needed to substitute treatment with several antipsychotics or high doses of previous antipsychotic treatment. In this study, INVEGA SUSTENNA doses greater than 234 mg were administered as a single injection by combining the suspension from multiple kits into one syringe.⁶ However, INVEGA SUSTENNA is available commercially as a calibrated suspension and proper preparation is required to form a homogenous suspension prior to administration. Therefore, commercial doses of INVEGA SUSTENNA should not be combined or administered in divided injections.⁷ Previous antipsychotics included: RLAI (n=16), OLA (n=3), fluphenazine/14 days (n=2), HAL (n=2), RIS (n-2), amisulpride (n=1), ARI (n=1), QUE (n=1), ZIP (n=1) and zuclopentixol/14 days (n=1) Clinical assessments were carried out via the CGI-S, WHO-DAS, MARS, and CAN.	A total of 30 patients (mean age: 42.3 years; 53% male) met the criteria for lack of effectiveness at 3 months and received an average INVEGA SUSTENNA dose of 356.8 mg/28 days (range: 273 mg to 624 mg/28 days) during the 3-year study. *Efficacy/Effectiveness* At 36 months, there was a significant decrease in the concurrent use of other psychiatric medications compared to baseline (P<0.05). Significant improvements were observed in clinical severity, functioning and adherence beginning at month 6. Mean assessment scale scores at baseline to endpoint, respectively included: CGI-S: 5.4 to 3.8 (P<0.01) MARS: 3.9 to 9.1 (P<0.001) CAN: 15.1 to 8.9 (P<0.01) WHO-DAS: self-care (2.4 to 1.1 [P<0.005]); occupational (3.5 to 2.3 [P<0.01]); family (3.3 to 2.1 [P<0.01]); social impairment (3.6 to 2.1 [P<0.05]) In addition, hospitalizations significantly decreased from baseline to endpoint (1.4 vs 0.2, respectively; P<0.001). The retention rate after 3 years was 90% (n=27/30) with three discontinuations. Two were due to lack of effectiveness (CGI-S≥5 after 3 months of treatment), and one due to metabolic syndrome. *Safety* Forty percent of patients reported as least one mild AE with somnolence, EPS, and injection site pain most commonly reported. An overall non-significant decrease in prolactin was reported. There were no incidences of gynecomastia or galactorrhea, however two patients reported sexual dysfunction potentially related to a prolactin elevation. Compared to baseline, significantly fewer patients required treatment for parkinsonism after 3 years of INVEGA SUSTENNA treatment (P<0.05). Significant weight loss was observed from baseline to endpoint (average weight: 79.1 kg vs 71.2kg, respectively; P<0.05). Overall, two patients experienced a weight gain ≥7%.
Coppola (2012)² conducted a 56-week, open-label, 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 (Treatment A, n=186) received a second deltoid IM injection of INVEGA SUSTENNA 234 mg on day 8 followed by 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 PK sampling (Treatment B, n=26) received a second IM injection of INVEGA SUSTENNA 78-234 mg (flexible dose) on day 8 (deltoid or gluteal muscle) followed by 12 once-monthly injections starting on day 36 (deltoid or gluteal muscle).	*Mean INVEGA SUSTENNA mode dose:* Treatment A: 234 mg Treatment B: 171 mg *Mean total duration of exposure:* 250 days (plasma concentrations were within the expected range) *Efficacy:* Completed study: 113/212 104 patients received INVEGA SUSTENNA 234 mg throughout study 209 patients had ≥1 post-baseline psychiatric assessment; 30% of patients had ≥30% improvement in PANSS scores from baseline to endpoint No clinically meaningful changes in PSP and CGI-S scores reported from baseline to endpoint *Safety:* 87% of patients experienced ≥1 TEAE; majority of events were mild to moderate in severity 27 patients discontinued due to a TEAE 11 patients discontinued due to a serious TEAE TEAEs occurring in ≥10% of all patients: nasopharyngitis (17.5%) insomnia (15%) injection-site pain (15%) tachycardia (13%) headache (13%) 15.6% of patients experienced serious TEAEs, most commonly: worsening of symptoms of schizophrenia (5%); psychotic disorder (3%) No deaths reported
Abbreviations: AE, adverse event; ARI, aripiprazole; CAN, Camberwell Assessment of Need; CGI-S, Clinical Global Impression-Severity Scale; ECG, electrocardiogram; EPS, extrapyramidal symptoms; HAL, haloperidol; IM, intramuscular; Inj, injection; LS, least squares; MARS, Medication Adherence Rating Scale; OLA, olanzapine; PANSS, Positive and Negative Syndrome Scale; PK, pharmacokinetic; PBO, placebo; PSP, Personal and Social Performance Scale; QUE, quetiapine; RIS, risperidone; RLAI, risperidone long-acting injection; TEAE, treatment-emergent adverse event; WHO-DAS, World Health Organization Disability Assessment Schedule; ZIP, ziprasidone.

PHARMACOKINETIC SIMULATIONS

PK simulations were conducted to investigate the steady state plasma concentration profiles of the highest recommended INVEGA SUSTENNA maintenance dose (234 mg every 4 weeks) versus two higher than recommended or more frequently administered dosing regimens.⁵ Each of the three dosing regimens were simulated with the recommended initiation dosing of 234 mg on day 1 followed by 156 mg on day 8. From day 36 onward the three dosing regimens were: 1) 234 mg every 4 weeks, 2) two 156 mg injections every 4 weeks, and 3) 234 mg every 3 weeks. All doses were simulated with administration in the deltoid muscle. Simulated plasma concentration profiles of the dosing regimens indicated that steady state peak paliperidone levels with two 156 mg injections every 4 weeks were higher than 234 mg every 3 weeks. The two higher/more frequent dosing regimens produced higher plasma concentrations than the recommended highest maintenance dose regimen of 234 mg every 4 weeks. See Figure: Simulated Plasma Paliperidone Concentrations for more details. The higher/more frequent INVEGA SUSTENNA dosing regimen simulations are not aligned with the currently approved labeling for INVEGA SUSTENNA and have not been validated in clinical trials.

Simulated Plasma Paliperidone Concentrations

Post hoc analysis

In a post hoc analysis of 23 patients receiving an average per patient maintenance dose of INVEGA SUSTENNA 237 mg (152.0 mg eq), INVEGA SUSTENNA was well tolerated and patients were clinically stable.⁸

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 21 August 2024.

References

Show

1	Carter N. Extended-release intramuscular paliperidone palmitate: a review of its use in the treatment of schizophrenia. Drugs. 2012;72(8):1137-1160.
2	Coppola D, Liu Y, Gopal S, et al. A one-year prospective study of the safety, tolerability and pharmacokinetics of the highest available dose of paliperidone palmitate in patients with schizophrenia. BMC Psychiatry. 2012;12(26).
3	Pandina G, Lindenmayer J, Lull J, et al. A randomized placebo-controlled study to assess the efficacy and safety or 3 doses of paliperidone palmitate in adults with acutely exacerbated schizophrenia. J Clin Psychopharmacol. 2010;30:235-244.
4	Haskins J, Sliwa JK, Ma YW, et al. Efficacy and safety of 234 mg initiation dose and 3-fixed maintenance doses of paliperidone palmitate-a once-monthly injectable atypical antipsychotic. Poster presented at: the US Psychiatric and Mental Health Congress; November 2-5, 2009; Las Vegas, NV.
5	Data on File. Janssen Research and Development; 2012.
6	Fernandez-Miranda J, Diaz-Fernandez S. Tolerability of effective high doses of paliperidone palmitate in patients with severe resistant schizophrenia. Int Clin Psychopharmacol. 2017;32:6-12.
7	Gopal S, Gassmann-Mayer C, Palumbo J, et al. Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia. Curr Med Res Opin. 2010;26(2):377-387.
8	Vega M, Arques S, Vazquez-Norguerol R, et al. Clinical results of the use of the highest approved dose of monthly paliperidone palmitate. PICTURE sub-analysis study. Poster presented at: The 31st European College of Neuropsychopharmacology Congress; October 6-9, 2018; Barelona, Spain.