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Risperidone extended-release injectable suspension

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Oral antipsychotic nonadherence is a significant contributor to relapse in patients with schizophrenia spectrum disorders. Long-acting injectable (LAI) antipsychotics have been developed to provide sustained antipsychotic exposure, with evidence that use of LAIs significantly reduces hospitalization rates.1 One limiting factor in transitioning patients to certain LAIs is the need for prolonged oral coverage at the onset of treatment for agents that cannot be loaded. Nonadherence with this bridging oral therapy places the patient at risk for symptom exacerbation until effective antipsychotic plasma levels are achieved from the LAI.2 Although risperidone is one of the more widely used antipsychotics for treating schizophrenia, until recently the only available LAI preparation, risperidone microspheres (Risperdal Consta), required 3 weeks of oral coverage upon initiation.3

To obviate this need for extended oral bridging, a novel LAI form of risperidone was developed utilizing a proprietary subcutaneous injectable formulation that provides effective plasma active moiety levels within 1 week of the injection and sustained antipsychotic levels with monthly usage. Risperidone extended-release injectable suspension (investigational name RBP-7000, brand name Perseris) was approved on July 27, 2018 for the treatment of adults with schizophrenia (Table 1). The efficacy and safety of RBP-7000 was demonstrated in a pivotal 8-week, double-blind, placebo-controlled trial of adult patients age 18 to 55 with acute exacerbation of schizophrenia.4

Clinical implications

Oral medication nonadherence remains a significant public health issue for patients with schizophrenia, with an estimated 50% of patients failing to achieve 80% adherence even when enrolled in clinical trials specifically designed to track adherence.5 Although LAI atypical antipsychotics have been available since the approval of Risperdal Consta, the LAI form of risperidone, and both LAI forms of aripiprazole, were not designed to be loaded. A 1-day initiation regimen for aripiprazole lauroxil has been developed to avoid the need for 3 weeks of oral medication coverage,6,7 but aripiprazole monohydrate and risperidone microspheres mandate oral bridging of 2 and 3 weeks, respectively.2 Because one of the primary indications for LAI antipsychotic therapy is oral medication nonadherence, this prolonged period of oral coverage creates a risk for symptom exacerbation when the bridging period occurs outside of a controlled setting, as is common when patients are discharged from inpatient hospitalization.

One solution to this problem has its antecedents in the development of the Atrigel biodegradable injectable polymer, which was designed to deliver prolonged medication exposure after subcutaneous injection.8 This biodegradable polymer drug delivery system suspends and dissolves the medication of interest (in this case, risperidone) in a poly DL-lactide-coglycolide gel and its biocompatible carrier.9 The viscous liquid undergoes a phase transition upon contact with tissue fluids after subcutaneous injection, resulting in an implant that releases risperidone in a controlled manner as it is resorbed. Importantly, the kinetic parameters of RBP-7000 are such that effective drug levels are seen within the first week without the need for oral coverage.10

Use in adults with schizophrenia. After establishing tolerability with oral risperidone, the recommended doses are 90 mg or 120 mg monthly, which correspond to oral daily risperidone doses of 3 mg or 4 mg. RBP-7000 must be administered as a subcutaneous abdominal injection by a health care professional. It is recommended that the patient be in the supine position for the injection and that the injection sites be rotated monthly among 4 quadrants in the abdominal region. The injection volumes for the 90 mg and 120 mg doses are 0.6 mL and 0.8 mL, respectively.10 As the gel implant becomes firmer, the patient will notice a lump for several weeks that will decrease in size over time. Patients should be advised not to rub or massage the injection site, and to be aware of the placement of any belts or clothing with waistbands.10

Pharmacologic profile, adverse reactions

Risperidone is an atypical antipsychotic that has been commercially available in the U.S. since December 29, 1993, and its adverse effect profile is well characterized. The most common adverse effects associated with risperidone include those related to dopamine D2 antagonism, metabolic adverse effects, and an increase in serum prolactin. In the 12-month long-term safety study of RBP-7000, 1-minute post-dose injection site pain scores (on a 100-point scale) were highest on Day 1 (mean of 25) and decreased over time with subsequent injections (14 to 16 following the last injection).10

Continue to: How the Atrigel system works

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