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 milligrams 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.

PHARMACOKINETIC (PK) STUDIES

The following population PK model based simulations were performed to support the dosing recommendations for missed doses for INVEGA TRINZA.^3,4

Simulations performed using the INVEGA TRINZA formulation in the maintenance phase at week 12 ±1 to 3 weeks showed that minimum plasma concentration (C_min) and maximum plasma concentration (C_max) changes were relatively small (see Tables: Plasma Paliperidone Concentrations During Maintenance Therapy with INVEGA TRINZA 819 mg at Week 12, -1 to -3 Weeks and Plasma Paliperidone Concentrations During Maintenance Therapy with INVEGA TRINZA 273 mg at Week 12, +1 to +3 Weeks; Figures: Plasma Paliperidone Concentrations During Maintenance Therapy 1-3 Weeks Before Regularly Scheduled INVEGA TRINZA 819 mg Injection and Plasma Paliperidone Concentrations During Maintenance Therapy 1-3 Weeks After Regularly Scheduled INVEGA TRINZA 273 mg Injection).³ Therefore, on exceptional occasions, patients may be given an injection up to 2 weeks before or after the 3-month time point.

Simulations performed in which a missed dose occurred <4 months since the last deltoid injection of INVEGA TRINZA 819 mg showed that similar paliperidone concentrations were achieved  when the same dose of INVEGA TRINZA was reinitiated at 13, 14, and 15 weeks after the last injection (see Figure: Predicted Paliperidone Plasma Concentrations for Missed Dose Occurring <4 Months Since Last Injection of INVEGA TRINZA 819 mg).^3,4

Simulations performed in which a missed dose occurred 4 months to 9 months since the last deltoid injection of INVEGA TRINZA 819 mg showed that similar paliperidone concentrations were achieved when treatment was reinitiated with 2 deltoid injections of INVEGA SUSTENNA formulation 156 mg 1 week apart (day 1 and day 8), followed by an injection of INVEGA TRINZA 819 mg every 12 weeks (see Figure: Predicted Paliperidone Plasma Concentrations for Missed Dose Occurring 4 to 9 Months Since Last Injection of INVEGA TRINZA 819 mg).^3,4

Simulations performed in which a missed dose occurred >9 to 12 months since the last deltoid injection of 819 mg showed that similar paliperidone concentrations were achieved when treatment was re-initiated with deltoid injections of INVEGA SUSTENNA 234 mg on day 1, INVEGA SUSTENNA 156 mg on day 8, followed by 3 additional monthly doses of INVEGA SUSTENNA 234 mg, and then continued with INVEGA TRINZA 819 mg injections every 12 weeks (see Figure: Predicted Paliperidone Plasma Concentrations for Missed Dose Occurring >9 to 12 Months Since Last Injection of INVEGA TRINZA 819 mg).^3,4

Although this PK study was conducted using deltoid injections, a separate PK analysis demonstrated that between 30 and 33 days, C_max between injection sites were not significantly different (11% to 12% higher following deltoid administration compared to gluteal administration).¹

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 27 March 2024.