Summary

• Steady state plasma concentrations of RISPERDAL CONSTA are reached after 4 injections (administered every 2 weeks) and are maintained for 4-6 weeks after the last injection.¹
• After a single intramuscular injection of RISPERDAL CONSTA, there is a small initial release of the drug, followed by a lag time of 3 weeks. Upon erosion of the microspheres and subsequent absorption of risperidone, the apparent half-life of RISPERDAL CONSTA is 3-6 days. Therefore, the elimination phase of RISPERDAL CONSTA is complete approximately 7-8 weeks after the last injection.¹
• There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotics to RISPERDAL or treating patients with concomitant antipsychotics.²
• In a pharmacokinetic simulation model to evaluate antipsychotic plasma concentrations after discontinuation, discontinuation of risperidone long-acting injection (RLAI) resulted in the active moiety concentration continuing to approximate the steady-state concentration for approximately 3-5 weeks due to delay in release (main release of drug is maintained from 4-6 weeks after injection). A rapid decline of active moiety concentration is observed with near zero concentration reached by week 5.³
• Doses of 25, 50, or 75 mg of RLAI every 2 weeks were bioequivalent to daily oral doses of 2, 4, or 6 mg of oral risperidone, respectively, in a study designed to compare the bioavailability of risperidone and the active moiety (risperidone and 9-OH-risperidone) after oral risperidone and RLAI administration. Mean steady-state peak moiety levels and plasma fluctuations were lower with the RLAI compared with oral risperidone.⁴
• The decision of how to convert/switch antipsychotics must be based on clinical judgment, individual patient assessment, and pharmacokinetic properties of the drugs involved.

PRODUCT LABELING

Please refer to the following sections of the enclosed Full Prescribing Information that are relevant to your inquiry: CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.

CLINICAL STUDIES

Published Literature

Samtani et al (2012)³ conducted a pharmacokinetic 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 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 described complete discontinuation. Pharmacokinetic modeling was used to predict plasma concentrations over an 8-week period following treatment discontinuation. Discontinuation of RLAI resulted in the active moiety concentration continuing to approximate the steady-state concentration for approximately 3-5 weeks due to delay in release (main release of drug is maintained from 4-6 weeks after injection). A rapid decline of active moiety concentration is observed with near zero concentration reached by week 5.

The authors concluded that formulations with a longer half-life result in a resilient pharmacokinetic profile in the event of treatment discontinuation. Upon clinically advised discontinuation, the prolonged-release characteristics of medications with a long half-life need to be considered.

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 08 August 2024.