Practical guidance for dosing and switching paliperidone palmitate treatment in patients with schizophrenia

Abstract

Objective:

This article overviews the recommended dosing strategies for the treatment of schizophrenia patients using the recently FDA-approved once-monthly long-acting injectable atypical antipsychotic, paliperidone palmitate.

Methods:

Using pharmacokinetic (PK), efficacy and safety data from clinical trials and a comprehensive population PK simulation model, dosing recommendations for paliperidone palmitate have been generated.

Results:

The recommended initiation regimen is 150 mg eq. paliperidone palmitate (234 mg) on Day 1 followed by 100 mg eq. paliperidone palmitate (156 mg) on Day 8, each administered into the deltoid muscle, using a 1-inch 23 gauge (G) needle in those <90 kg and a 1.5-inch 22 G needle in those ≥90 kg. No oral supplementation is required. Monthly maintenance doses of paliperidone palmitate range from 25–150 mg eq. (39–234 mg; recommended dose of 75 mg eq. [117 mg]) injected into the deltoid (using weight-adjusted needle) or gluteal (using 1.5 inch 22 G needle) muscle. The Day 8 dose may be administered ±2 days and monthly doses ±7 days, without a clinically significant impact on plasma concentrations. In patients with mild renal impairment (creatinine clearance [CrCL]: 50–80 mL/min), dosage should be adjusted. No dose adjustment is required in patients with mild or moderate hepatic impairment; no data currently exist regarding severe hepatic impairment. Elderly patients with normal renal function should receive the same dosage as younger adult patients with normal renal function. In the event of an age-related decline in CrCL, dosage should be adjusted accordingly. Paliperidone palmitate treatment can be initiated the day after discontinuing previous oral antipsychotic treatment. Paliperidone palmitate should be initiated at the next scheduled injection, and monthly thereafter, in patients switching from other long-acting injectable antipsychotics, including long-acting risperidone.

Conclusions:

These data provide practical guidance to clinicians on how to use paliperidone palmitate in adult patients with schizophrenia.

Key words::

• Dosing
• Long-acting injectable
• Paliperidone palmitate
• Schizophrenia
• Switching

Transparency

Declaration of funding

The development of this paper was supported by funding from Johnson & Johnson Pharmaceuticals LLC.

Declaration of financial/other relationships

S.G., M.N.S., C.G.-M. and J.P. have disclosed that they are employees of Johnson & Johnson. M.S. and C.G.-M. have disclosed that they also own Johnson & Johnson stocks. L.A. has disclosed that he is an employee of Ortho-McNeil Janssen Scientific Affairs, LLC, a subsidiary of Johnson & Johnson. R.S. has disclosed that he has worked with a number of pharmaceutical companies as investigator, including Johnson & Johnson, and has conducted clinical trials on paliperidone palmitate. R.S. has been a speaker for Johnson & Johnson.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank Samantha Kew, Medicus International, for providing editorial assistance in the development of this paper.

The data in this paper were presented as posters at the Annual Meeting of the College of Psychiatric and Neurologic Pharmacists, Jacksonville, FL, USA, April 19–22, 2009 (Poster no. 19; Samtani M.N. et al.); at the Annual Meeting of the American Psychiatric Association, San Francisco, CA, USA, May 16–21, 2009 (Poster no. NRI-046; Samtani M.N. et al.); at the Annual Meeting of the College of Psychiatric and Neurologic Pharmacists, Jacksonville, FL, USA, 19–22 April 2009 (Poster no. 21; Samtani M.N. et al.); at the Annual Meeting of the American Psychiatric Association 2009, San Francisco, CA, USA, May 16–21, 2009 (Poster no. NRI-036; Samtani M.N. et al.); and at the New Clinical Drug Evaluation Unit, Hollywood, FL, USA, 29 Jun – 2 Jul 2009 (Poster no. II-62; Samtani M.N. et al. and Poster no. I-68).

The sponsors were involved in the writing and reviewing of this manuscript.