Population Pharmacokinetic–Based Strategies for Switching Patients with Schizophrenia Between Long-Acting Injectable Formulations of Risperidone: R064766 or RBP-7000 to TV-46000

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This analysis used pharmacokinetic (PK) modeling to characterize dosing conversions and switching strategies from R064766, a once-every-2-weeks, intramuscular long-acting injectable antipsychotic (LAI) formulation of risperidone microspheres, and RBP-7000, a subcutaneous (sc) LAI formulation of risperidone administered in the abdomen once monthly (q1m), to TV-46000, a q1m or once-every-2-months (q2m) sc LAI formulation of risperidone. Total active moiety (TAM; risperidone + 9-OH risperidone) concentration–time profiles were simulated on the basis of published population PK models with virtual populations of 5000 patients. Simulations were performed to predict TAM exposures when switching to TV-46000 q1m and q2m 2–6 weeks after the last steady-state R064766 injection and 4 weeks after the last dose of RBP-7000. Comparable doses of oral risperidone, TV-46000, R064766, and RBP-7000 were identified. Initiating TV-46000 4–6 weeks after the last dose of R064766 resulted in similar trends for maximal (Cmax) and minimal (Cmin) plasma concentration ratios after the first injection for all TV-46000 doses and durations (q1m, q2m) compared with R064766 at steady state. Initiating TV-46000 q1m 4 weeks after the last dose of RBP-7000 resulted in slightly higher, but generally comparable, average plasma concentrations, Cmax, and Cmin at first dose and at steady state for TV-46000 compared with RBP-7000; Cmin of TV-46000 q2m and RBP-7000 were also comparable. Similar trends in plasma concentrations were observed for both back-of-the-upper-arm and abdominal administration when switching from R064766 and RBP-7000 to TV-46000. These simulations revealed switching to TV-46000 4–6 weeks after the last dose of R064766 and 4 weeks after the last dose of RBP-7000 provided generally comparable PK exposures at first dose and steady state of TV-46000. Clinician discretion will determine which switching strategy is most appropriate in context based on factors such as patient preference, scheduling convenience, and concerns about tolerability. Injected drugs that last in the body for weeks or months can be used to treat people living with schizophrenia. There are differences in the amount of drug in the blood over time between different brands of drugs, which can make it difficult for clinicians to figure out how much of a new drug to use and how long to wait between injections when switching patients from one injectable drug to another. The aim of this study was to use computer models to test different options when switching from one drug to another. The options studied included how much time to wait between the last dose of one drug and the first dose of another. The different dose amounts were also studied. In this work, the drugs being switched from are given either once every 2 weeks (R064766) or once per month (RBP-7000). The drug that is being switched to (TV-46000) is given once per month or once every 2 months. The predictions showed that TV-46000 injected 4–6 weeks after the last dose of R064766 and 4 weeks after the last dose of RBP-7000 did not significantly affect the amount of active drug in the blood over time. This study gives clinicians more information about how they can switch patients from one injectable drug to another. The decision to switch from one drug to another will be based on many factors, such as the patient’s preferences, convenience, and any concerns about safety or symptoms returning.