Summary

• Safety data involving concomitant use of INVEGA TRINZA with other antipsychotics is limited. Since paliperidone is the major active metabolite of risperidone, caution should be exercised when INVEGA TRINZA is coadministered with risperidone or oral paliperidone for extended periods of time.¹
• In a randomized, open-label, multicenter, parallel-group, phase-1 study to evaluate the pharmacokinetics (PK), safety, and tolerability of INVEGA TRINZA formulation, patients were permitted to continue their existing antipsychotic medications as long as they did not interfere with the PK of paliperidone. Prohibited medications included oral risperidone, paliperidone, clozapine, ziprasidone, thioridazine, risperidone long-acting injection, paliperidone palmitate 1-month extended release injectable suspension, and long-acting formulations of other neuroleptic drugs (e.g., haloperidol decanoate, prolixin decanoate, etc).²
• Extrapolated PK simulations were conducted to examine the paliperidone plasma levels achieved with the addition of oral paliperidone extended-release (ER) tablets to INVEGA TRINZA injections.³ By visual inspection, the addition of oral paliperidone ER 3 mg/day to INVEGA TRINZA 410 mg or 546 mg in the last two or four weeks of the 12-week dosing interval appeared to lessen the fluctuation in paliperidone plasma levels achieved over the dosing interval. However, the addition of oral paliperidone ER 6 mg/day or 9 mg/day in the last two or four weeks of the 12-week dosing interval appeared to cause a substantial increase in paliperidone plasma levels. Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials.  
• Concomitant administration of INVEGA TRINZA and oral paliperidone ER is not consistent with product labeling for either product, and is therefore not recommended.
• A literature search did not identify any additional information on the concomitant use of INVEGA TRINZA with any oral antipsychotic medications.

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 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.

PHARMACOKINETIC MODELING

Extrapolated PK simulations were conducted to examine the paliperidone plasma levels achieved with the addition of oral paliperidone extended-release (ER) 3, 6, or 9 mg/day to INVEGA TRINZA 410 mg or 546 mg (via deltoid or gluteal injections) in the last two or four weeks of every 12-week dosing interval. See Figures: Concomitant daily use of oral paliperidone ER in the last 2 weeks of each 12-week INVEGA TRINZA 410 mg dosing interval for (deltoid or gluteal injections), Concomitant daily use of oral paliperidone ER in the last 2 weeks of each 12-week dosing interval for INVEGA TRINZA 546 mg (deltoid or gluteal injections), Concomitant daily use of oral paliperidone ER in the last 4 weeks of each 12-week dosing interval for INVEGA TRINZA 410 mg (deltoid or gluteal injections), and Concomitant daily use of oral paliperidone ER in the last 4 weeks of each 12-week dosing interval for INVEGA TRINZA 546 mg (deltoid or gluteal injections).³

By visual inspection, the addition of oral paliperidone ER 3 mg/day to INVEGA TRINZA 410 mg or 546 mg in the last two or four weeks of the 12-week dosing interval appeared to lessen the fluctuation in paliperidone plasma levels over the dosing interval. However, the addition of oral paliperidone ER 6 mg/day or 9 mg/day in the last two or four weeks of the 12-week dosing interval appeared to cause a substantial increase in paliperidone plasma levels.  In addition, the steady-state C_max achieved with the addition of paliperidone ER 3 mg/day in the last two to four weeks of the 12-week dosing interval was generally similar to that observed with INVEGA TRINZA 410 mg or 546 mg administered alone every 12 weeks. See Tables: Comparison of C_max and C_min for INVEGA TRINZA 410 mg and 546 mg (deltoid and gluteal) every 12 weeks and INVEGA TRINZA 410 mg and 546 mg (deltoid and gluteal) every 12 weeks + paliperidone ER 3, 6, and 9 mg/day in the last 2 weeks of each INVEGA TRINZA 12-week dosing interval, and Comparison of C_max and C_min for INVEGA TRINZA 410 mg and 546 mg (deltoid and gluteal) every 12 weeks and INVEGA TRINZA 410 mg and 546 mg (deltoid and gluteal) every 12 weeks + paliperidone ER 3, 6, and 9 mg/day in the last 4 weeks of each INVEGA TRINZA 12-week dosing interval.

• Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials. Concomitant administration of INVEGA TRINZA and oral paliperidone ER is not consistent with product labeling for either product, and is therefore not recommended.

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.