Summary

• INVEGA HAFYERA (paliperidone palmitate 6-month [PP6M]) should be administered once every 6 months. Missing doses of INVEGA HAFYERA should be avoided. Patients may be given the injection up to 2 weeks before or 3 weeks after the scheduled 6-month time point.¹
• Pharmacokinetic (PK) simulations were performed to compare the median C_max and C_trough of dosing deviations within the dosing window around the regularly scheduled 6-month dosing interval at steady-state with INVEGA HAFYERA.²
• Based on PK simulations, dosing up to 2 weeks before or after the scheduled 6-month time point after INVEGA HAFYERA steady-state results in relatively small changes in exposure. The decrease in trough concentrations at steady state with INVEGA HAFYERA with dosing 3 weeks after the 6-month time point, may be acceptable based on the body of evidence available from current and prior paliperidone clinical trials.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 INVEGA HAFYERA dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA HAFYERA doses expressed as 1,092 and 1,560 mg of paliperidone palmitate are equal to 700 and 1,000 mg eq. of paliperidone, respectively.

ASSESSMENT OF DOSING EVERY 22 or 27 Weeks versus every 26 weeks

Pharmacokinetic simulations were performed to assess dosing windows around the regularly scheduled 6-month dosing interval after steady-state with INVEGA HAFYERA. These simulations evaluated whether a dosing deviation within the dosing window resulted in a clinically acceptable change in paliperidone concentration.² Simulations were conducted with:

• INVEGA HAFYERA 1,560 mg administered 1 or 2 weeks earlier than the scheduled 6month time point
• INVEGA HAFYERA 1,092 mg administered 1, 2, or 3 weeks later than the scheduled 6month time point

The INVEGA HAFYERA 1,560 mg dose was used to simulate the scenario where shortening the dosing interval has the biggest impact on the C_max of the higher dose.²

The INVEGA HAFYERA 1,092 mg dose was used to simulate the scenario where extending the dosing interval has the biggest impact on the C_trough of the lower dose.

See Table: Median C_max and C_trough and % Change of INVEGA HAFYERA Q24W Versus 1 and 2 Weeks Earlier With 1,560 mg and 1, 2 and 3 Weeks Later With 1,092 mg

Based on these simulations, patients at steady-state with INVEGA HAFYERA receiving their next INVEGA HAFYERA injection up to 2 weeks before or after the scheduled 6-month time point, are predicted to have relatively small changes in exposures. The decrease in trough concentrations in patients at steady-state with INVEGA HAFYERA receiving their next INVEGA HAFYERA injection 3 weeks after the 6-month time point may be acceptable based on the body of evidence available from current and prior paliperidone clinical trials.²

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 23 December 2024.