Summary

• If INVEGA HAFYERA is discontinued, its prolonged-release characteristics must be considered.
• Due to its extremely low water solubility, INVEGA HAFYERA 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 is predicted to last longer than 18 months.¹
• The median apparent half-life of paliperidone following a single INVEGA HAFYERA of either 1,092 or 1,560 mg was 148 and 159 days, respectively.¹
• The concentration of paliperidone remaining in the circulation 18 months after dosing of 1,560 mg 6-month paliperidone palmitate extended-release injectable suspension stopped is estimated to be 18% of the average steady-state levels.¹
• Based on pharmacokinetic (PK) modeling simulations, paliperidone concentrations ≥7.5 ng/mL, associated with ≥60% D₂-receptor occupancy,² were maintained for 14 to 20 months after discontinuation of INVEGA HAFYERA doses of 1,092 and 1,560 mg.³ 

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate can 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 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.

CLINICAL DATA

DISCONTINUATION FOLLOWING MULTIPLE DOSES

Paliperidone concentrations ≥7.5 ng/mL were maintained for 14 to 20 months after discontinuation of INVEGA HAFYERA 1,092 and 1,560 mg, see Figure: Predicted Plasma Concentrations After Discontinuation of INVEGA HAFYERA 1,092 and 1,560 mg at Steady State.³ A 7.5 ng/mL paliperidone concentration is associated with a 60% D₂-receptor occupancy.² A central D₂-receptor occupancy of 60 to 80% is generally thought to be required for antipsychotic efficacy.⁴

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 06 March 2025.