Summary

• This information is intended to be a concise summary of representative clinical data; not all available published literature is incorporated into this response.
• Please refer to the following section of the full PRESCRIBING INFORMATION relevant to your inquiry: PHARMACOKINETICS.¹
• After a single intramuscular injection of RISPERDAL CONSTA is given, there is a small initial release of the drug (<1% of the dose), followed by a lag time of 3 weeks. The main release of the drug starts from 3 weeks onward, is maintained from 4 to 6 weeks, and subsides by 7 weeks after the injection. Therefore, oral antipsychotic supplementation should be given during the first 3 weeks of treatment with RISPERDAL CONSTA.¹
• A systematic review identified 20 studies that evaluated therapeutic drug monitoring of RISPERDAL CONSTA.²
  • In 6 studies, the ratio of risperidone to 9-hydroxyrisperidone (9OHrisperidone) ranged from 0.24 to 0.74, with a weighted mean of 0.48 in 329 patients.
  • In 6 studies, the concentration vs dose (C/D) ratio ranged from 7.4 to 9.7 ng/mL/mg/day, with a weighted mean of 8.8 ng/mL/mg/day in 297 patients.
• Doses of 25, 50, or 75 mg of RISPERDAL CONSTA every 2 weeks (Q2W) were bioequivalent to daily oral doses of 2, 4, or 6 mg of oral risperidone, respectively, in an open-label, 15-week (N=86) study comparing the bioavailability of risperidone and its active moiety (risperidone and 9-OH-risperidone) after oral risperidone and RISPERDAL CONSTA administration.³
• In a 2-part multicenter, open-label study (study 1, n=170; study 2, n=53), RISPERDAL CONSTA 50 mg administered in the deltoid muscle was found to be bioequivalent in peak and total exposure to RISPERDAL CONSTA 50 mg injected in the gluteal muscle. The treatment ratios for maximum plasma concentration (C_max) and AUC of deltoid (37.5 mg dose normalized to 25 mg) vs gluteal (25 mg) injections were within the predefined range for bioequivalence.⁴
• In a 12-week, open-label trial evaluating the pharmacokinetics (PK) and efficacy of a direct switch from conventional depot antipsychotics (flupenthixol deconate, fluphenazine deconate, haloperidol deconatel, clopenthixol) to RISPERDAL CONSTA in Chinese patients (N=25), the C/D ratio and the mean daily dose of RISPERDAL CONSTA for most patients was low for the first 2 weeks but was stable at weeks 8 and 12. At week 12, patients who received final doses of 25 mg had significantly lower mean (standard deviation [SD]) levels of the active moiety (20.1 [13.8] ng/mL) than those who received final doses of 37.5 mg (39.6 [26.7] ng/mL; P=0.06). The plasma concentration of the active moiety was not associated with Positive and Negative Syndrome Scale (PANSS) scores, Extrapyramidal Symptom Rating Scale (ESRS) scores, or prolactin levels.⁵
• A 48-week, single-blind, single-center, randomized trial compared the PK of RISPERDAL CONSTA with oral risperidone (N=50) to determine equivalent switching doses.⁶
  • Patients who were stable with oral risperidone at doses of ≤4 mg/day, >4 to ≤6 mg/day, and >6 mg/day were switched to RISPERDAL CONSTA at doses of 25, 37.5, and 50 mg Q2W, respectively.
  • During the first 24 weeks after the switch, 9-OH-risperidone metabolites were significantly (P=0.003) reduced from baseline with RISPERDAL CONSTA vs oral risperidone, and no significant difference was observed in the change from baseline in serum risperidone (P=0.834) and total metabolites (P=0.081).
  • Based on these findings, the authors suggested that patients on oral risperidone <3 mg/day should receive RISPERDAL CONSTA 25 mg Q2W, while those on oral risperidone >3 to ≤5 mg/day should receive RISPERDAL CONSTA 37.5 mg Q2W. The higher dose of RISPERDAL CONSTA 50 mg Q2W was recommended for patients previously receiving oral risperidone >5 mg/day.
• In an open-label, nonrandomized study that evaluated the PK and central D₂ receptor occupancy of RISPERDAL CONSTA at doses of 25, 50, and 75 mg (N=13), a small first peak of plasma drug concentration was observed 8-24 hours after the first injection in all 3 dosage groups. Apparent steady state plasma concentrations occurred from the fourth injection onwards, were maintained for 4-5 weeks after the last injection, and declined thereafter with a half-life of 4-6 days. Higher doses of RISPERDAL CONSTA were generally associated with increased D₂ receptor occupancy (25 mg, 25‑48%; 50 mg, 59-83%; 75 mg, 62-72%).⁷
• In a 6-month, open-label, nonrandomized study evaluating the association between the levels of risperidone and 9-OH-risperidone, clinical outcomes, and tolerability in patients initiated on RISPERDAL CONSTA 25-50 mg Q2W (N=30), risperidone and 9OHrisperidone were positively correlated (r=0.4; P=0.02), and mean plasma concentrations increased in a dose-dependent manner (P=0.05 for 50 mg vs 25 mg); however, there were substantial variations among patients on the same dose. There was no difference in the plasma concentrations of the active moiety, risperidone, and 9-OH-risperidone between responders and nonresponders.⁸
• Modeling studies have evaluated the PK outcomes of oral and long-acting injectable formulations of risperidone and paliperidone,⁹ compared the PK of oral risperidone with that of RISPERDAL CONSTA and oxybutynin,¹⁰ compared the plasma concentrations of oral risperidone with those of RISPERDAL CONSTA,¹¹ and estimated blood levels in various clinical scenarios during treatment with RISPERDAL CONSTA.¹²
• No dose equivalency studies have been conducted between RISPERDAL CONSTA and other antipsychotics based on therapeutic response.
• Additional publications, identified during a literature search, have been referenced for your convenience.^13-16

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 30 October 2024.