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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2013-05-01
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| Series: | Neuropsychiatric Disease and Treatment |
| Online Access: | http://www.dovepress.com/expansion-of-guidance-for-the-day-8-initiation-dose-of-paliperidone-pa-a13096 |
| _version_ | 1819202526637981696 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-23T04:05:25Z |
| format | Article |
| id | doaj.art-90eb92f46b6142469fd8224a6c3cebc8 |
| institution | Directory Open Access Journal |
| issn | 1176-6328 1178-2021 |
| language | English |
| last_indexed | 2024-12-23T04:05:25Z |
| publishDate | 2013-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Neuropsychiatric Disease and Treatment |
| spelling | doaj.art-90eb92f46b6142469fd8224a6c3cebc82022-12-21T18:00:39ZengDove Medical PressNeuropsychiatric Disease and Treatment1176-63281178-20212013-05-012013default721730Expansion of guidance for the day 8 initiation dose of paliperidone palmitate to avoid a missed doseSamtani MNNuamah IGopal SRemmerie BSliwa JKAlphs LMahesh 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 pharmacokineticshttp://www.dovepress.com/expansion-of-guidance-for-the-day-8-initiation-dose-of-paliperidone-pa-a13096 |
| spellingShingle | 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 Neuropsychiatric Disease and Treatment |
| title | 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_short | 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 |
| url | http://www.dovepress.com/expansion-of-guidance-for-the-day-8-initiation-dose-of-paliperidone-pa-a13096 |
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