Dataset Information

Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose.

ABSTRACT: BACKGROUND:Paliperidone palmitate (PP) is a long-acting injectable formulation of an atypical antipsychotic, paliperidone. Its dose can be expressed in milligram or milligram equivalents (mg eq) of active paliperidone (39, 78, 117, 156, and 234 mg of PP correspond to 25, 50, 75, 100, and 150 mg eq of paliperidone). The recommended initiation dosing regimen for PP is 150 [day 1]/100[day 8] mg eq. Labeling guidance allowed a ± 2 day window for the day 8 injection that provides more flexibility with patient scheduling and avoids missing the day 8 initiation dose. Recently, expansion of the day 8 dosing window from ±2 to ±4 days has been approved in the United States based on results obtained from the model-based simulations and review of safety data presented here. METHODS:The predicted exposure for the recommended initiation regimen of PP was compared with day 1/day 4, and day 1/day 12 dosing scenarios; each scenario was compared with the highest clinically evaluated initiation regimen (150[day 1]/150[day 8] mg eq) and to the recommended 6 mg/day oral dose of extended-release paliperidone. RESULTS:Simulated exposures with PP 150 mg eq on day 1 and 100 mg eq on days 4, 8, or 12 overlap considerably, with ±3 ng/mL variation in median maximum plasma concentrations. Based upon pharmacokinetic bridging/bracketing, the peak concentration with PP 150/100 mg eq [days 1/4] was lower than that with the highest initiation regimen. Exposures for PP 150 mg eq on day 1 and 100 mg eq on days 4, 8, or 12 were maintained close to those of 6 mg of paliperidone extended-release. CONCLUSION:These simulations indicate that using the expanded dosing window of ±4 days has little effect on paliperidone exposure. A review of the overall pattern of treatment-emergent adverse events did not identify any new safety risks associated with the expanded dosing window.

SUBMITTER: Samtani MN

PROVIDER: S-EPMC3665573 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose.

Samtani Mahesh N MN Nuamah Isaac I Gopal Srihari S Remmerie Bart B Kern Sliwa Jennifer J Alphs Larry L

Neuropsychiatric disease and treatment 20130520

<h4>Background</h4>Paliperidone palmitate (PP) is a long-acting injectable formulation of an atypical antipsychotic, paliperidone. Its dose can be expressed in milligram or milligram equivalents (mg eq) of active paliperidone (39, 78, 117, 156, and 234 mg of PP correspond to 25, 50, 75, 100, and 150 mg eq of paliperidone). The recommended initiation dosing regimen for PP is 150 [day 1]/100[day 8] mg eq. Labeling guidance allowed a ± 2 day window for the day 8 injection that provides more flexibi ...[more]

PMID: 23723704

Similar Datasets

Project description:ObjectiveTo examine the tolerability of the recommended initiation doses for once-monthly injectable paliperidone palmitate in patients who have recently been diagnosed with schizophrenia and for whom high doses may pose tolerability concerns.MethodsA post hoc analysis from a 13-week double-blind study of patients with schizophrenia randomized 1:1:1:1 to placebo or paliperidone palmitate at 25, 100, or 150 mg equivalents (mg eq) of paliperidone (corresponding to 39, 156, or 234 mg respectively). This analysis focused on the recently diagnosed subgroup (≤5 years; N = 146) who received the recommended initiation dosage of paliperidone palmitate [150 mg eq on day 1 (n = 109) followed by 100 mg eq on day 8 (n = 39)] or placebo (n = 37). Adverse events (AEs), reported in ≥2% of patients receiving paliperidone palmitate during days 1-7 or ≥5% during days 8-36, and in a higher percentage of patients receiving paliperidone palmitate than placebo, were identified. AE relative risks (RRs) and 95% confidence intervals (CIs) were determined. A RR was considered potentially significant when its 95% CI did not include 1.ResultsOverall, day 1-7 AE rates were 37.6% (41 of 109) and 29.7% (11 of 37) with paliperidone palmitate and placebo respectively; injection site pain (5.5% versus 2.7%, RR 2.0; 95% CI 0.25 to 16.37), agitation (4.6% versus 2.7%; RR 1.7; 95% CI 0.21 to 14.06), and headache (3.7% versus 0.0%; RR 3.1; 95% CI 0.17 to 56.41) met the ≥2% criteria. Day 8-36 AE rates were 41.0% (16 of 39) and 37.8% (14 of 37) with paliperidone palmitate and placebo respectively; anxiety (5.1% versus 0.0%; RR 4.8; 95% CI 0.24 to 95.76) met the ≥5% criteria. Key limitations were that some patients may have been ill for a significant time before formal diagnosis and that the number of patients is low in this subgroup, limiting the ability to detect statistical significance for AE RRs.ConclusionsPaliperidone palmitate initiation doses (150 mg eq day 1, 100 mg eq day 8) were tolerated in this subgroup of patients who were recently diagnosed with schizophrenia, with no unexpected findings. Although the same size was small, these data identified AEs that may be encountered during the week and month after initiation dosing. These findings may assist clinicians when paliperidone palmitate is considered an appropriate treatment choice for these patients.

Project description:ObjectiveFirst-month data of a 13-week acute schizophrenia study were used to compare paliperidone palmitate to oral risperidone during initiation of long-acting injectable risperidone.DesignDouble-blind, randomized study.SettingOutpatient or inpatient.ParticipantsAdults with established (≥1 year) schizophrenia. Those assigned to risperidone long-acting injectable (n=460) received 25mg on Days 8 and 22 with oral risperidone (l-6mg) supplementation for the first 28 days. The paliperidone palmitate group (n=453) received 150mg eq. on Day 1, l00mg eq. on Day 8, and oral placebo supplementation for the first 28 days.MeasurementsPositive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical Global Impression-Severity score, and responder rate (percentage of patients with ≥30% reduction in PANSS total score). An analysis of covariance model estimated least-square mean differences between treatment groups. A post-hoc analysis of efficacy data for the period of interest, i.e., at the time points before and after the first 28 days, was conducted.ResultsPositive and Negative Syndrome Scale, Personal and Social Performance Scale, Clinical global Impression-Severity scores showed similar efficacy between the treatment groups during the first weeks of treatment, corresponding to the risperidone long-acting injection initiation period. Mean Positive and Negative Syndrome Scale total score at baseline was 84.7 for paliperidone palmitate and 84.4 for oral risperidone, on Day 22 was 73.6 and 74.1, respectively, and on Day 36 was 71.8 and 72.8, respectively. Overall incidence of adverse events in the first 28 days was generally similar (45% for paliperidone palmitate vs. 35% for oral risperidone), except for injection site pain (4.6% vs. 0.7%). Similar active moiety plasma concentrations were obtained during this period.ConclusionDuring the first month, paliperidone palmitate without oral supplementation has similar efficacy and safety to oral risperidone (during initiation of risperidone long-acting injectable) in acutely exacerbated schizophrenia.

Project description:PURPOSE:Reducing the dosing frequency of antipsychotics (APs) with long-acting injectables (LAIs) such as once-monthly paliperidone palmitate (PP1M) can improve adherence and clinical outcomes for schizophrenia patients. This US study compared physical and psychiatric comorbidity-related outcomes, AP adherence, healthcare resource utilization (HRU), and costs pre- and post-transition to PP1M among schizophrenia patients treated with oral risperidone/paliperidone pre-PP1M transition. METHODS:Health insurance claims from the IQVIA™ PharMetrics Plus database (01/01/2012-07/31/2018) were used to identify adults with???2 schizophrenia diagnoses,???1 claim for PP1M, and???30 days of treatment with oral risperidone/paliperidone in the 60 days before the first PP1M claim (i.e., the index date). Comorbidity-related outcomes, adherence to APs (measured via the proportion of days covered [PDC]), all-cause per-patient-per-month (PPPM) HRU, and all-cause PPPM medical, pharmacy, and total costs (i.e., sum of medical and pharmacy costs) during the 6-month periods pre- and post-transition to PP1M were compared using generalized estimating equation models adjusted for repeated measurements. Analyses were replicated in the subset of patients with???1 all-cause inpatient stay pre-PP1M transition. FINDINGS:Among 427 schizophrenia patients transitioning from oral risperidone/paliperidone to PP1M, the mean age was 41.1 years and 37.9% were female. Following the PP1M transition, patients were less likely to have claims with a diagnosis for psychoses (odds ratio [OR] 0.41; P?<?0.001), hypertension (OR 0.80; P?=?0.011), depression (OR 0.70; P?<?0.001), drug abuse (OR 0.60; P?<?0.001), substance-related and addictive disorders (OR 0.73; P?=?0.003), bipolar and related disorders (OR 0.59; P?<?0.001), sleep-wake disorders (OR 0.68; P?=?0.017), anxiety disorders (OR 0.78; P?=?0.034), and other conditions that may require a focus of clinical attention (OR 0.58; P?<?0.001). Mean PDC by APs was higher post-PP1M (mean?=?0.81) versus pre-PP1M (mean?=?0.68) transition. Post-PP1M, patients were less likely to have an all-cause emergency room visit (OR 0.51; P?<?0.001) or inpatient stay (OR 0.39; P?<?0.001) compared to pre-PP1M. All-cause total healthcare costs remained similar post- versus pre-transition to PP1M (mean monthly cost difference [MMCD]?=?$228; P?=?0.260). Pharmacy costs increased post-PP1M (MMCD?=?$960; P?<?0.001), but were offset by decreasing medical costs (MMCD?=?- $732; P?<?0.001), largely driven by lower costs related to inpatient stays (MMCD?=?- $695; P?<?0.001) and emergency room visits (MMCD?=?- $63; P?<?0.001). For patients with???1 all-cause inpatient stay pre-PP1M transition (N?=?177), a more pronounced improvement in comorbidity-related outcomes, a more pronounced reduction in HRU, and a reduction in total healthcare costs (MMCD?=?- $1308; P?<?0.001) were observed post-transition to PP1M. IMPLICATIONS:Among schizophrenia patients in the US, transitioning to PP1M following oral risperidone/paliperidone treatment was associated with improved comorbidity-related outcomes, higher adherence, and a reduction in HRU, while remaining cost neutral. Furthermore, patients with???1 all-cause inpatient stay pre-PP1M transition had significantly lower total healthcare costs post-PP1M transition.

Project description:ObjectiveTo evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics.MethodsIn this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods.ResultsA total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: -11.3 [21.38], P<0.0001, primary endpoint). Subgroup analysis revealed greater improvements among patients with worse disease severity at baseline: PANSS ≥70 versus <70 (mean [SD] change: -23.1 [24.62] vs -4.7 [15.98], P<0.0001 each). Secondary efficacy endpoints such as Clinical Global Impression of Schizophrenia (CGI-SCH), Medication Satisfaction Questionnaire (MSQ) scores showed significant improvements (P<0.0001) from baseline; 33.3% patients achieved symptom remission. In mirror analyses set (N=474), PP significantly (P<0.0001) reduced mean number of hospitalization days/person/year (12-month: 74.3 vs 19.7; 18-month: 74.3 vs 18.9) as well as percentage of patients requiring hospitalization in past 12 months (12-month: 39.7% vs 24.6%; 18-month: 39.7% vs 25%), and PP treatment increased the proportion of patients not requiring hospitalization (12-month: 60.3% vs 75.4%; 18-month: 60.3% vs 75%) from retrospective to prospective period. Adverse events (≥15%) were extrapyramidal symptoms-related (31.3%), injection-site pain (18.6%), and insomnia (15.2%).ConclusionPP was efficacious and generally tolerable with significant reductions observed in both number of hospitalizations and days spent in hospital.

Dataset Information

Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose.

Publications

Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets