Summary

• Due to its extremely low water solubility, INVEGA TRINZA dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The release of the drug starts as early as day 1 and lasts for as long as 18 months.¹
• The concentration of paliperidone remaining in the circulation 18 months after dosing of 819 mg INVEGA TRINZA is stopped is estimated to be 3% (following deltoid injection) or 7% (following gluteal injection) of the average steady-state levels.¹
• The median apparent half-life (t_1/2) of paliperidone following INVEGA TRINZA administration over the dose range of 273-819 mg ranged from 84-95 days following deltoid injections and 118-139 days following gluteal injections.¹
• Paliperidone concentrations ≥7.5 ng/mL, associated with ≥60% D₂-receptor occupancy, were maintained for 10 to 14 months after discontinuation of INVEGA TRINZA doses of 546 mg and 819 mg.²

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 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.

CLINICAL DATA

DISCONTINUATION FOLLOWING MULTIPLE DOSES

Gopal et al (2015)^2,3 performed population pharmacokinetic simulations for missed doses of INVEGA TRINZA, which included paliperidone plasma concentrations over time after stopping INVEGA TRINZA treatment after multiple doses. Paliperidone concentrations ≥7.5 ng/mL were maintained for 10 to 14 months after discontinuation of INVEGA TRINZA 546 mg and 819 mg. A 7.5 ng/mL paliperidone concentration is associated with a 60% D₂-receptor occupancy.⁴ A central D₂receptor occupancy of 60 to 80% is generally thought to be required for antipsychotic efficacy.⁵ Therefore, the missed dose simulations for >9 months since the last dose of INVEGA TRINZA support reinitiation with at least 4 months of treatment with paliperidone palmitate 1-month extended-release injectable suspension before transitioning to INVEGA TRINZA. See Figure: Predicted Plasma Concentrations of INVEGA TRINZA 819 mg After Discontinuation Followed by Initiation 10, 11, and 12 Months Later.

DISCONTINUATION FOLLOWING SINGLE DOSE

Ravenstijn et al (2015)⁶ assessed the safety and tolerability of INVEGA TRINZA following a single intramuscular (deltoid or gluteal) injection of 117-819 mg in patients with schizophrenia or schizoaffective disorder. INVEGA TRINZA was slowly absorbed as indicated by a time to maximum plasma concentration (t_max) of approximately 23 to 34 days and t_1/2 of approximately 2 to 4 months. The t_1/2 was slightly longer in the gluteal dose groups compared with the deltoid dose groups. See Figure: Median Plasma Concentration-Time Profile of Paliperidone After Administration of INVEGA TRINZA in the Deltoid and Gluteal Muscle.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 08 January 2025.