Summary

• Always check the needle hub for signs of damage or leakage after attaching the needle to the syringe using a gentle twisting motion. A cracked needle hub can result in leakage of the medication and incomplete administration of the dose.¹
• Slowly inject the entire contents of the syringe intramuscularly, deep into the selected deltoid or gluteal muscle of the patient. Do not administer by any other route.^1,2
• INVEGA TRINZA is a suspension, and the syringe is not calibrated. Therefore, administration of INVEGA TRINZA should be in a single injection. Do not administer the dose in divided injections.^1,2
• No clinical data are available on administering partial or divided doses of INVEGA TRINZA.
• Extrapolated pharmacokinetic (PK) simulations were conducted to predict plasma concentrations when giving a 546 mg dose of INVEGA TRINZA in two divided doses (273 mg injections) or 819 mg of INVEGA TRINZA in two divided doses (410 mg injections).³

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, respectively.

PHARMACOKINETIC MODELING

No systematically collected data are available on using two doses of INVEGA TRINZA 273 mg in place of an INVEGA TRINZA 546 mg injection. However, extrapolated pharmacokinetic (PK) simulations were developed to predict the paliperidone plasma concentrations when a 546 mg dose of INVEGA TRINZA is given as two simultaneous injections of 273 mg in opposite deltoid or gluteal muscles.³ The PK simulation (see Figure: Comparison of INVEGA TRINZA 546 mg [deltoid or gluteal] every 12 weeks and INVEGA TRINZA 546 mg every 12 weeks with two injections of 273 mg at day 288 [in opposite deltoid or gluteal muscles]) depicts a comparison of the predicted paliperidone plasma concentration for simulated subjects who received INVEGA TRINZA 546 mg every 12 weeks versus subjects who received INVEGA TRINZA 546 mg every 12 weeks with two simultaneous injections of INVEGA TRINZA 273 mg administered in opposite deltoid or gluteal muscles at day 288 in place of one of the INVEGA TRINZA 546 mg injections (deltoid or gluteal). Thereafter, INVEGA TRINZA 546 mg was administered every 12 weeks in both groups.

Higher minimum (C_min) and maximum (C_max) paliperidone plasma concentrations were achieved with the two simultaneous INVEGA TRINZA 273 mg injections administered on the same day in opposite deltoid or gluteal muscles versus those achieved from one INVEGA TRINZA 546 mg injection (see Table: Comparison of C_min and C_max for INVEGA TRINZA 546 mg [deltoid or gluteal] every 12 weeks and INVEGA TRINZA 546 mg [deltoid or gluteal] every 12 weeks with two injections of 273 mg at day 288). Importantly, these simulations represent extrapolations of a pharmacokinetic model and have not been investigated in clinical trials.

No systematically collected data are available on using two doses of INVEGA TRINZA 410 mg in place of an INVEGA TRINZA 819 mg injection. However, extrapolated pharmacokinetic (PK) simulations were developed to predict the paliperidone plasma concentrations when an 819 mg dose of INVEGA TRINZA is given as two simultaneous injections of 410 mg in opposite deltoid or gluteal muscles.  The PK simulation (see Figure: Comparison of INVEGA TRINZA 819 mg [deltoid or gluteal] every 12 weeks with INVEGA TRINZA 819 mg every 12 weeks with two injections of 410 mg at day 288 [in opposite deltoid or gluteal muscles]) depicts a comparison of the predicted paliperidone plasma concentration for simulated subjects who received INVEGA TRINZA 819 mg every 12 weeks versus subjects who received INVEGA TRINZA 819 mg every 12 weeks with two simultaneous injections of INVEGA TRINZA 410 mg administered at day 288 in place of one of the INVEGA TRINZA 819 mg injections.  Thereafter, INVEGA TRINZA 819 mg was administered every 12 weeks in both groups.

Higher minimum (C_min) and maximum (C_max) paliperidone plasma concentrations were achieved with the two simultaneous INVEGA TRINZA 410 mg injections administered on the same day in the same location versus those achieved from one INVEGA TRINZA 819 mg injection (see Table: Comparison of C_min and C_max for INVEGA TRINZA 819 mg [deltoid or gluteal] every 12 weeks and INVEGA TRINZA 819 mg [deltoid or gluteal] every 12 weeks with two injections of 410 mg at day 288). Importantly, these simulations represent extrapolations of a pharmacokinetic model and have not been investigated in clinical trials.

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.