Summary

• Indications and Usage: INVEGA HAFYERA is indicated for the treatment of schizophrenia in adult patients who have been adequately treated with INVEGA SUSTENNA^® (paliperidone palmitate 1-month) for at least four months or INVEGA TRINZA^® (paliperidone palmitate 3-month) following at least one 3-month injection cycle.¹
• Transitioning to INVEGA HAFYERA from monthly INVEGA SUSTENNA: When transitioning to INVEGA HAFYERA from INVEGA SUSTENNA, to establish a consistent maintenance dose, it is recommended that the last two monthly doses of INVEGA SUSTENNA be the same dosage strength at 156 mg or 234 mg. Initiate INVEGA HAFYERA at the time when the next monthly INVEGA SUSTENNA dose was to be scheduled with an INVEGA HAFYERA dose based on the previous INVEGA SUSTENNA dose. See local labeling for more information.¹
• Pharmacokinetic (PK) Modeling: PK simulations were conducted to investigate which frequency of administration of 1,560 mg paliperidone palmitate 6-month formulation (PP6M) may result in similar paliperidone exposure to a 234 mg dose of the paliperidone palmitate 1-month formulation (PP1M) administered every 3 weeks. Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials.²
• More frequent administration of INVEGA SUSTENNA (eg, every 3 weeks) or INVEGA HAFYERA (eg, every 5 months) is not consistent with the Prescribing Information for either product, and is therefore not recommended.

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 SUSTENNA and INVEGA HAFYERA dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 25, 50, 75, 100, and 150 mg eq. are equal to 39, 78, 117, 156, and 234 mg of paliperidone palmitate, respectively.
• INVEGA HAFYERA doses expressed as 700 and 1,000 mg eq. are equal to 1,092 or
  1,560 mg of paliperidone palmitate, respectively.

PK MODELING

PK simulations were developed to investigate the frequency of administration of the 1,560 mg dose of PP6M that may result in similar paliperidone exposure to a 234 mg dose of PP1M administered every 3 weeks. This simulation assessed the paliperidone plasma PK profile when 234 mg PP1M was administered every 3 weeks (with the exception of the first three maintenance doses which were every 4 weeks) until steady-state was achieved, and then either 234 mg PP1M every 3 weeks was continued, or there was a switch to 1,560 mg PP6M every 4, 5, or 6 months. Other available PP1M doses (39, 78, 117, and 156 mg) were not included in the extrapolated PK modeling simulation for this scenario.²

Importantly, these simulations represent extrapolations of a pharmacokinetic model, and have not been investigated in clinical trials. Additionally, more frequent administration of INVEGA SUSTENNA (eg, every 3 weeks) or INVEGA HAFYERA (eg, every 5 months) is not consistent with the Prescribing Information for either product, and is therefore not recommended.²

Comparison of steady-state C_max for 234 mg PP1M (deltoid) every 3 weeks with C_max after a switch to 1,560 mg PP6M (gluteal) from 234 mg PP1M every 3 weeks, resulted in a 59.5% increase in C_max. Comparison of steady-state C_min with C_min after switching to 1,560 mg PP6M (gluteal) every 4 months, 5 months, or 6 months from 234 mg PP1M (deltoid) every 3 weeks, resulted in a 20.2%, 37.2%, and 48.8% decrease in C_min, respectively. Please see Table: Comparison of Median C_max and Median C_min for 234 mg PP1M (deltoid) every 3 weeks at steady-state and 234 mg PP1M every 3 weeks at steady-state followed by a switch to 1,560 mg PP6M (gluteal) every 4, 5, or 6 months. Although no clear exposure-response relationship could be identified from the PP6M Phase 3 study, an increase in C_max may result in risk of adverse events while decrease in C_min may result in risk of relapse.²

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 13 September 2024.