Practical guidance for dosing and switching from paliperidone palmitate 1 monthly to 3 monthly formulation in schizophrenia

Abstract

Objective:

This commentary summarizes recommended dosing strategies for a recently developed 3 monthly long-acting injectable1 (LAI) formulation of paliperidone palmitate (PP3M) for the treatment of schizophrenia in adults.

Methods:

Recommendations for different dosing scenarios are based on the pharmacokinetic, efficacy and safety outcomes from phase 1 and phase 3 studies, population pharmacokinetic models, and model based simulations.

Results:

Switching to PP3M treatment is recommended only in patients previously treated with once monthly paliperidone palmitate LAI (PP1M) for at least 4 months. The first injection of PP3M (175 to 525 mg equivalent [eq.]) should be given at the time of next scheduled injection of PP1M as a 3.5-fold multiple of the last PP1M dose (50–150 mg eq.), with a dosing window of ±1 week. Following that first injection of PP3M, once-every-three-months maintenance injections with PP3M are recommended, with a dosing window of ±2 weeks. The doses of PP3M can be administered in either deltoid (≥90 kg: 1.5 inch 22 G needle; <90 kg: 1.0 inch 22 G needle) or gluteal muscles (1.5 inch 22 G needle regardless of weight). In patients with mild renal impairment (creatinine clearance: 50–80 mL/min), a 25% dose reduction in PP1M and subsequent switching to a corresponding 3.5-dose multiple of PP3M (but not exceeding 350 mg eq.) is recommended. Appropriate dosing is recommended in elderly patients with diminished renal function not exceeding mild renal impairment. Similarly to PP1M, PP3M is not recommended in patients with moderate/severe renal impairment. Like PP1M, no dosage adjustment is required in patients with mild or moderate hepatic impairment or elderly patients with normal renal function.

Conclusions:

These data provide clinical guidelines for the optimum use of PP3M in patients with schizophrenia previously treated with PP1M for at least 4 months.

Registration:

ClinicalTrials.gov identifier: NCT01559272 and NCT01529515.

Keywords: :

• 3 monthly formulation
• Paliperidone palmitate
• Schizophrenia

Transparency

Declaration of funding

This study was funded by Janssen Research & Development LLC, NJ, USA. The sponsor also provided a formal review of this manuscript.

Author contributions: M.N.S. had primary role in the study design, data analysis and interpretation. P.R. was the clinical pharmacology leader, contributing to the data analysis and interpretation. I.N. was the statistical lead for the study and had primary roles in the statistical analyses and data interpretation. A.S. and J.B. were the safety physicians for the studies, and were also involved in data analysis and interpretation. D.H. and S.G. are the clinical leader and compound development team leader for paliperidone palmitate 3 month formulation, and had primary roles in the study design, analyses and data interpretation.

All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors. All authors had access to the study data and made the final decision about where to present these data.

Declaration of financial/other relationships

S.G., A.V., P.N., P.R., I.N., J.A.B.V., J.B., A.S., D.H., and M.N.S. have disclosed that they are employees of Janssen Research & Development LLC and are shareholders in the parent company (Johnson & Johnson).

CMRO peer reviewer 1 has disclosed that he has received sponsorship and grants/research funding from Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis and Servier. He is also a consultant to AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Novartis, Schwabe, and Servier. He is also on the speakers’ bureau of Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Lundbeck, Neuraxpharm, Pierre Fabre, Pfizer, Schwabe, and Servier. CMRO peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Elodie Plan PhD, Mats Magnusson PhD, and Niclas Jonsson PhD, from Pharmetheus AB for their contribution to the study analysis. The authors also thank Ashwini Patil MS (SIRO Clinpharm Pvt Ltd) for medical writing assistance of this commentary, Wendy P. Battisti PhD (Janssen Research & Development) for providing editorial support, and the participants and investigators of all PP1M and PP3M studies.