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 of paliperidone, respectively.

sWITCHING FROM RISPERIDONE LONG-ACTING INJECTION

PK Modeling Simulation

Samtani et al (2010)¹ presented results on strategies for switching from RLAI to PP1M.  Results from PK modeling simulations suggest that patients previously stabilized with different doses of RLAI can attain similar steady-state exposure to active moiety during maintenance treatment with monthly doses of PP1M; these results are shown in Table: Doses of RLAI and PP1M Needed to Attain Similar Exposure to Active Moiety at Steady-State.

The PK modeling scenarios of switching from RLAI 25 mg every 2 weeks to PP1M 78 mg administered monthly (low-dose scenario) and switching from RLAI 50 mg every 2 weeks to PP1M 156 mg administered monthly (high-dose scenario) are depicted in the Figure: Switching from RLAI to PP1M.

In each scenario, plasma concentrations of the active moiety are maintained at concentrations close to steady-state right after the switch from RLAI to PP1M. The recommended initiation regimen for PP1M (234 mg on day 1 and 156 mg on day 8) is not required for this transition. In addition, no oral antipsychotic supplementation is required.

Case Series

Montalvo et al (2013)⁴ conducted a prospective, observational case series study of patients with a psychotic disorder (n=11, mean age 26.6 years) who were treated with RLAI for at least six months and experienced hyperprolactinemia. The patients were switched to INVEGA SUSTENNA, with the monthly paliperidone dose in mg eq being double the every-2-week RLAI dose. Please refer to DOSAGE STRENGTH INFORMATION section above for information regarding the conversion of mg eq of paliperidone to milligrams of paliperidone palmitate. There was a 25.5% reduction in prolactin levels from baseline to three months after the switch from RLAI to INVEGA SUSTENNA (P=0.041).

Switching from other Long-acting injectable Antipsychotics

PALMFlex

Schreiner et al (2015)⁵ reported results in patients with symptomatic non-acute schizophrenia switched to INVEGA SUSTENNA from RLAI or conventional depot antipsychotics (intention-to-treat efficacy/safety: RLAI [n=56]; haloperidol (HAL) decanoate [n=53], flupentixol (FPT) decanoate [n=35], fluphenazine (FLU) decanoate [n=44], or zuclopenthixol (ZUC) decanoate [n=42]).

Study Design/Methods

• The first INVEGA SUSTENNA dose (78-234 mg) was administered in place of the next scheduled depot injection.
• Flexible INVEGA SUSTENNA doses of 78-234 mg were administered monthly thereafter (±7 days).

Results

• Mean modal INVEGA SUSTENNA maintenance doses ranged from 162.6-175.5 mg.
• At the last observation carried forward (LOCF) endpoint, the following percentages of patients, per LAI switch group, had a ≥20% improvement in PANSS total scores: RLAI: 61.1%; FPT decanoate: 61.8%; FLU decanoate: 59.1%; HAL decanoate: 54.7%; ZUC decanoate: 53.7.
• The most common treatment-emergent adverse events (≥5% any switch group), primarily rated mild to moderate in intensity, were anxiety, headache, psychotic disorders, schizophrenia, injection site pain, insomnia, somnolence, suicidal ideation, weight increased, hallucination and constipation.
• All switch groups experienced a significant reduction in ESRS scores from baseline to LOCF endpoint.

Gopal et al (2014)³ analyzed outcomes from the PALMFLEX trial along with postmarketing databases to compare relapse rates following a switch from RLAI to INVEGA SUSTENNA versus a switch from oral or other LAI antipsychotics to INVEGA SUSTENNA.

Post Hoc Analysis - PALMFLEX

Incidences of symptom worsening or relapse appeared similar between the switch from RLAI (17.9%) or other LAI antipsychotics (11.4% to 16.7%) to INVEGA SUSTENNA as well as the switch from oral risperidone (12.3%) or other oral antipsychotics (19.3%) to INVEGA SUSTENNA.

Postmarketing

Utilizing a Worldwide Safety Database (SCEPTRE), loss of efficacy or relapse was identified in 100 cases after switching from RLAI to INVEGA SUSTENNA.

In the first review (cumulative cases received through June 30, 2012), cases with INVEGA SUSTENNA dosing information and at least the start date of therapy were identified.

In just 2 of the 49 cases, the dose and timing of INVEGA SUSTENNA in relation to RLAI was consistent with the recommended switching strategy.

• Case 1: Relapse was reported within 30 days following a switch from RLAI 37.5 mg every 2 weeks to INVEGA SUSTENNA 117 mg in a patient who was stable on RLAI (exact latency not reported).
• Case 2: While stability of the patient’s underlying disease was not reported, breakthrough symptoms occurred 13 days following the second 156 mg dose of INVEGA SUSTENNA.

Clinical trial and spontaneous cases were included in the second review (July 1, 2012 through April 16, 2013). Of the 12 cases identified, the dosing regimen was not provided for 5 cases and the recommended switching regimen was not followed in 3 cases. Of the 4 cases where the recommended switch regimen was followed, 1 patient was reported stable at the time of the switch.

Latency (start of INVEGA SUSTENNA therapy to onset of lack of effect/relapse) could be calculated or estimated in 73 of the 100 cases from both reviews. The onset of lack of efficacy/relapse occurred within 30 days of INVEGA SUSTENNA initiation in 41 of the 73 cases.

Drug ineffective, psychotic disorder and condition aggravated were the top three most frequently reported events in both reviews.

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 18 April 2024. In order to streamline this response, individual case reports were not included.