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

Mahesh N Samtani,1 Isaac Nuamah,1 Srihari Gopal,1 Bart Remmerie,2 Jennifer Kern Sliwa,3 Larry Alphs31Janssen Research and Development, LLC, NJ, USA; 2Janssen Research and Development, LLC, Division of Janssen Pharmaceutica NV, Beerse, Belgium; 3Janssen Scientific Affairs, LLC, NJ, USABackground: Pal...

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Autores principales:	Samtani MN, Nuamah I, Gopal S, Remmerie B, Sliwa JK, Alphs L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/90eb92f46b6142469fd8224a6c3cebc8
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spelling	oai:doaj.org-article:90eb92f46b6142469fd8224a6c3cebc82021-12-02T07:45:59ZExpansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose1176-63281178-2021https://doaj.org/article/90eb92f46b6142469fd8224a6c3cebc82013-05-01T00:00:00Zhttp://www.dovepress.com/expansion-of-guidance-for-the-day-8-initiation-dose-of-paliperidone-pa-a13096https://doaj.org/toc/1176-6328https://doaj.org/toc/1178-2021Mahesh N Samtani,1 Isaac Nuamah,1 Srihari Gopal,1 Bart Remmerie,2 Jennifer Kern Sliwa,3 Larry Alphs31Janssen Research and Development, LLC, NJ, USA; 2Janssen Research and Development, LLC, Division of Janssen Pharmaceutica NV, Beerse, Belgium; 3Janssen Scientific Affairs, LLC, NJ, USABackground: 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.Keywords: dosing window expansion, initiation regimen, long-acting-injectable, pharmacokinetic bridging, paliperidone palmitate, population pharmacokineticsSamtani MNNuamah IGopal SRemmerie BSliwa JKAlphs LDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2013, Iss default, Pp 721-730 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Samtani MN Nuamah I Gopal S Remmerie B Sliwa JK Alphs L Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
description	Mahesh N Samtani,1 Isaac Nuamah,1 Srihari Gopal,1 Bart Remmerie,2 Jennifer Kern Sliwa,3 Larry Alphs31Janssen Research and Development, LLC, NJ, USA; 2Janssen Research and Development, LLC, Division of Janssen Pharmaceutica NV, Beerse, Belgium; 3Janssen Scientific Affairs, LLC, NJ, USABackground: 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.Keywords: dosing window expansion, initiation regimen, long-acting-injectable, pharmacokinetic bridging, paliperidone palmitate, population pharmacokinetics
format	article
author	Samtani MN Nuamah I Gopal S Remmerie B Sliwa JK Alphs L
author_facet	Samtani MN Nuamah I Gopal S Remmerie B Sliwa JK Alphs L
author_sort	Samtani MN
title	Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
title_short	Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
title_full	Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
title_fullStr	Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
title_full_unstemmed	Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
title_sort	expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/90eb92f46b6142469fd8224a6c3cebc8
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Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed dose

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