Summary

• If INVEGA SUSTENNA is discontinued, its prolonged-release characteristics must be considered.¹
• Due to its extremely low water solubility, INVEGA SUSTENNA dissolves slowly after intramuscular (IM) injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. Following a single IM dose, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median time to reach maximum plasma concentration (T_max) of 13 days. The release of the drug starts as early as day 1 and lasts for as long as 126 days.²
• The median apparent half-life of paliperidone following INVEGA SUSTENNA single-dose administration over the dose range of 39 mg-234 mg ranged from 25 days-49 days.¹
• Based on pharmacokinetic (PK) modeling simulations following discontinuation of INVEGA SUSTENNA 117 mg every 4 weeks (at steady-state), there was a slow, steady decrease in active moiety plasma concentrations to 7.2 ng/mL at week 8 after discontinuation.³

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release (ER) 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 dosage strengths in the United States. The conversion factor from mg eq to mg is 1.56.

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

clinical DATA

Samtani et al (2012)³ conducted a PK simulation model to evaluate antipsychotic plasma concentrations after discontinuation or interruption of therapy with oral and long-acting injectable formulations of risperidone and paliperidone. The results for the long-acting injectable INVEGA SUSTENNA are presented below.

Study Design/Methods

• The simulation assumed individuals were at steady-state and then entered into 1 of 3 separate discontinuation/interruption scenarios, with medication-specific reinitiation strategies used in the interruption scenarios.
  • Scenario 1: Complete discontinuation
  • Scenario 2: One week of treatment interruption followed by administration of INVEGA SUSTENNA 117 mg every 4 weeks
  • Scenario 3: Four weeks of treatment interruption followed by administration of INVEGA SUSTENNA 117 mg on days 28 and 35 (weeks 4 and 5) and every 4 weeks thereafter
• PK modeling was used to predict plasma concentrations over an 8-9 week period following treatment discontinuation or interruption, and to determine the lowest concentrations during the modeled period as a percentage of the steady-state C_min in the two interruption scenarios.

Results

• Scenario 1: Discontinuation of INVEGA SUSTENNA led to a slow, steady decrease in plasma concentrations to 7.2 ng/mL in week 8.
• Scenario 2: A 1-week treatment interruption of INVEGA SUSTENNA led to a decrease in plasma concentrations to 90% of steady-state C_min.
• Scenario 3: A 4-week treatment interruption of INVEGA SUSTENNA led to a decrease in plasma concentrations to 64% of steady-state C_min. Upon reinitiation, there was a rapid reattainment of plasma concentrations.

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 23 December 2024.