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Risperidone extended-release injectable suspension

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Efficacy of RBP-7000 was established in an 8-week, double-blind, placebo-controlled trial of adult patients experiencing an acute exacerbation of schizo­phrenia (age 18 to 55).4 Eligible participants had:

  • An acute exacerbation of schizophrenia that occurred ≤8 weeks before the screening visit and would have benefited from psychiatric hospitalization or continued hospitalization
  • Positive and Negative Syndrome Scale (PANSS) total score between 80 and 120 at visit 1 and a score of >4 on at least 2 of the following 4 items: hallucinatory behavior, delusions, conceptual disorganization, or suspiciousness/persecution
  • The diagnosis of acute exacerbation of schizophrenia and PANSS total score were confirmed through an independent video-conference interview conducted by an experienced rater.

Participants were excluded if they:

  • Experienced a ≥20% improvement in PANSS total score between the initial screening visit and the first injection
  • had been treated at any time with clozapine for treatment-resistant schizophrenia
  • had met DSM-IV-TR criteria for substance dependence (with the exception of nicotine or caffeine) before screening.

During the initial screening visit, participants received a 0.25-mg tablet of oral risperidone on 2 consecutive days to assess the tolerability of risperidone.

Outcome. Participants were randomized in a 1:1:1 manner to placebo (n = 112) or 1 of 2 monthly doses of RBP-7000: 90 mg (n = 111) or 120 mg (n = 114). Using the least squares means of repeated-measures changes from baseline in PANSS total scores, there was a significant improvement in the difference in PANSS total scores from baseline to the end of the study compared with placebo: 90-mg RBP-7000, -6.148 points (95% confidence interval [CI], -9.982 to -2.314, P = .0004); 120-mg RBP-7000, -7.237 points (95% CI, -11.045 to -3.429, P < .0001). The absolute change from baseline in PANSS total score was -15.367 points for the 90-mg dose and -16.456 points for the 120-mg dose.4 Completion rates across all 3 arms were comparable: placebo 70.6%, RBP-7000 90 mg 77.6%, and RBP-7000 120 mg 71.4%.

Tolerability. In the 8-week phase III efficacy trial of RBP-7000, adverse effects occurring with an incidence ≥5% and at least twice the rate of placebo were weight gain (placebo 3.4%, 90 mg 13.0%, 120 mg 12.8%) and sedation (placebo 0%, 90 mg 7.0%, 120 mg 7.7%).10 Compared with baseline, participants had a mean weight gain at the end of the study of 2.83 kg in the placebo group, 5.15 kg in the 90-mg RBP-7000 group, and 4.69 kg in the 120-mg RBP-7000 group. There were no clinically significant differences at study endpoint in glucose and lipid parameters. Consistent with the known effects of risperidone, there were increases in mean prolactin levels during the 8-week study, the effects of which were greater for women. For men, mean prolactin levels from baseline to study end were: placebo: 9.8 ± 7.9 vs 9.9 ± 8.0 ng/mL; 90 mg: 8.9 ± 6.9 vs 22.4 ± 11.2 ng/mL; and 120 mg: 8.2 ± 5.2 vs 31.3 ± 14.8 ng/mL. For women, mean prolactin levels from baseline to study end were: placebo: 12.8 ± 11.7 vs 10.4 ± 8.0 ng/mL; 90 mg: 7.7 ± 5.3 vs 60.3 ± 46.9 ng/mL; and 120 mg: 10.9 ± 8.6 vs 85.5 ± 55.1 ng/mL. In the pivotal study, discontinuations due to adverse events were low across all treatment groups: 2.5% for placebo vs 0% for 90 mg and 1.7% for 120 mg.4 There was no single adverse reaction leading to discontinuation that occurred at a rate of ≥2% and greater than placebo in patients treated with RBP-7000.10 There were no clinically relevant differences in mean changes from baseline in corrected QT, QRS, and PR intervals, and in heart rate. Similarly, in the 12-month, long-term safety study, there were no clinically relevant changes in mean electrocardiography interval values from baseline to post-dose assessments.10

Using a 100-point visual analog scale (VAS), injection site pain scores 1 minute after the first dose decreased from a mean of 27 to the range of 3 to 7 for scores obtained 30 to 60 minutes post-dose. In the 12-month long-term safety study, 1-minute post-dose injection site pain VAS scores were highest on Day 1 (mean of 25) and decreased over time with subsequent injections (14 to 16 following last injection).10

Clinical considerations

Unique properties. RBP-7000 uses the established Atrigel system to provide effective antipsychotic levels in the first week of treatment, without the need for bridging oral coverage or a second loading injection. The abdominal subcutaneous injection volume is relatively small (0.6 mL or 0.8 mL).

Why Rx? The reasons to prescribe RBP-7000 for adult patients with schizophrenia include:

  • no oral coverage required at the initiation of treatment
  • effective plasma active moiety levels are seen within the first week without the need for a second loading injection
  • monthly injection schedule.

Dosing. The recommended dosage of RBP-7000 is 90 mg or 120 mg once monthly, equivalent to 3 mg/d or 4 mg/d of oral risperidone, respectively. Oral risperidone tolerability should be established before the first injection. No oral risperidone coverage is required. RBP-7000 has not been studied in patients with renal or hepatic impairment and should be used with caution in these patients. Prior to initiating treatment in these patients, it is advised to carefully titrate up to at least 3 mg/d of oral risperidone. If a patient can tolerate 3 mg/d of oral risperidone and is psychiatrically stable, then the 90-mg dose of RBP-7000 can be considered.10

Contraindications. The only contraindications for RBP-7000 are known hypersensitivity to risperidone, paliperidone (9-OH risperidone), or other components of the injection.

Bottom Line

RBP-7000 (Perseris) is the second long-acting injectable (LAI) form of risperidone approved in the U.S. Unlike risperidone microspheres (Consta), RBP-7000 does not require any oral risperidone coverage at the beginning of therapy, provides effective drug levels within the first week of treatment with a single injection, and uses a monthly dosing interval. RBP-7000 does not require loading upon initiation. The monthly injection is <1 mL, is administered in abdominal subcutaneous tissue, and uses the Atrigel system.

Related Resource

Drug Brand Names
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Tegretol
Doxycycline • Atridox
Leuprolide acetate injectable suspension • Eligard
Paliperidone palmitate • Invega Sustenna
Risperidone • Risperdal
Risperidone extended-release injectable suspension • Perseris
Risperidone long-acting injection • Risperdal Consta

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