Risperdal pi pdf

Population PK techniques provide a unified framework to characterise the PK of a compound by condensing observations from multiple studies while accounting for differences in patient factors and study design. While risperidone metabolism is known to be influenced by CYP2D6 genotype, the PK of the active moiety has been shown to be on average similar across different metabolic phenotypes, ie poor, intermediate, and extensive metabolisers. Additional covariate effects have been described elsewhere.

The population PK models described above were used to simulate SS PK profiles according to the following dosing regimens:. PP1M every 4 weeks deltoid or gluteal injections at doses of 25, 50, 75, , and mg equivalents mg eq. Initiation with deltoid injections of mg eq.

Since the primary purpose of this analysis was to establish dose conversion factors between the two drugs for maintenance treatment when PK SS can be assumed , the simulated PK profiles were depicted over a hypothetical time frame of 28 days at SS. The PP1M maintenance doses of 25, 50, 75, and mg eq. Table 1 summarises the PP1M dose levels that are projected to attain similar SS exposures to corresponding oral risperidone doses for maintenance treatment.

The average plasma concentration over the dosing interval is not affected. The transition from oral risperidone to PP1M must include the recommended initiation regimen of mg eq. Clinical factors related to adherence, efficacy and tolerability are critically important when establishing a suitable maintenance dose level in a given patient. In addition to PK considerations, clinical symptoms should always be considered when switching medications.

Patients undergoing a switch should be monitored closely before and after switching the medications. The sponsor of the study had roles in the study design and conduct; collection, analysis and interpretation of the data. Alberto Russu, Arun Singh, Maju Mathews, and Srihari Gopal were involved in study design, conduct, analysis and interpretation of data. Paulien Ravenstijn was the clinical pharmacokinetic leader, contributing to data analysis and interpretation.

Alberto Russu was the pharmacometric leader for the study and had the primary role in pharmacokinetic analyses and data interpretation. Jennifer Kern Sliwa and Edward Kim identified the customer need for this pharmacokinetic analysis and contributed to the development and review of this manuscript. All authors contributed to data interpretation, development and review of this manuscript and confirm that they have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

All authors had access to the study data, provided direction and comments on the manuscript, made the final decision about where to publish these data and approved submission to this journal. Authors also thank the study participants, without whom this study would never have been accomplished and all the investigators for their participation in this study.

Maintenance dose conversion between oral risperidone and paliperidone palmitate 1 month: Practical guidance based on pharmacokinetic simulations. The list of product names concerned is given in Annex I. This type of referral is triggered when Member States have adopted different decisions over the years for some medicines e. Please do not include any personal data , such as your name or contact details. Skip to main content. Veterinary regulatory Overview Research and development Marketing authorisation Post-authorisation.

Table of contents Overview Key facts All documents. Current status. This medicinal product belongs to the list of products identified in for SPC harmonisation. A Decision was issued by the European Commission on 7 October Much of this is conjecture, however, and is extrapolated from research on other LAI antipsychotics.

In clinical studies, RSQM has not been proven to prevent relapses. Risperidone subcutaneous monthly injection is the second formulation of a risperidone LAI and one of nine LAIs that are now available. With its projected similar efficacy and safety to risperidone biweekly LAI, RSQM offers the advantage of once-monthly dosing and no oral supplementation requirements. The rapid achievement of plasma concentrations near that of steady state concentrations within four to six hours suggests that RSQM may be useful in an acute setting.

Other LAIs cannot achieve this target concentration as rapidly or without the addition of loading doses or oral supplementation. Also, patients might choose SQ over IM administration because of convenience, which has been seen in preference-of-medication scores in health-related quality of life studies; interestingly, RSQM had higher pain VAS scores than risperidone biweekly LAI 27 vs.

Results from the pivotal phase 3 trial support the use of RSQM in acute patients, and not only in well-controlled patients who wish to transition to an LAI. There appears to be a role for RSQM in the inpatient psychiatric setting as well as the outpatient setting. However, there is a lack of robust, long-term data on efficacy, as patients in the phase 3 trial received only two doses of treatment. Pharmacokinetic studies show that RSQM mg, the highest strength available, is approximately equivalent to oral risperidone 4 mg.

But converting patients who require doses of oral risperidone exceeding 4 mg could pose a clinical challenge, as RSQM mg may not supply enough medication exposure and D 2 occupancy in those patients. Nasser et al. It is not known if the decreased injection frequency from every two weeks to every four weeks will further improve patient adherence and have a clinical and healthcare cost-savings effect on relapses.

Certain questions remain to be answered: Are clinical endpoints maintained? Do patients require further dose escalation and, if so, how is this done?

Is the depot able to be removed if serious adverse drug events are observed or if the patient requires abdominal surgery? Will patients initiate self-injurious behavior to attempt to remove or damage the implant lump? The answers may change future clinical opinion regarding RSQM; but at present, it appears to be an efficacious alternative treatment option for patients with schizophrenia. Disclosure: Dr.

Burdge and Dr. Karas report no financial or commercial interest in regard to this article. National Center for Biotechnology Information , U. Journal List P T v. Author information Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Patients were included in the study if they met the following criteria: Male or female aged 18—55 years.

They had received clozapine at any time for treatment-resistant schizophrenia. Laffont et al Using data from two clinical trials, a phase 1 randomized, open-label, single-ascending dose study and a phase 2a open-label, multiple-ascending dose study, Laffont et al.

Open in a separate window. Footnotes Disclosure: Dr. American Psychiatric Association. Washington, D. C: American Psychiatric Association; Practice guideline for the treatment of patients with schizophrenia. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature.

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Paliperidone palmitate once-monthly reduces risk of relapse of psychotic, depressive, and manic symptoms and maintains functioning in a double-blind, randomized study of schizoaffective disorder. Aripiprazole intramuscular depot as maintenance treatment in patients with schizophrenia: a week, multicenter, randomized, double-blind, placebo-controlled study.

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