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The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values

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Abstract

Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.

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Authors and Affiliations

  1. Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada

    Lik Hang N. Lee & Alasdair M. Barr

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    Charles Choi & Abby C. Collier

  3. British Columbia Mental Health and Addictions Research Institute, A3-938 W 28th Avenue, Vancouver, BC, V5Z 4H4, Canada

    Alasdair M. Barr, William G. Honer & Ric M. Procyshyn

  4. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    William G. Honer & Ric M. Procyshyn

Authors
  1. Lik Hang N. Lee
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  2. Charles Choi
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  3. Abby C. Collier
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  4. Alasdair M. Barr
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  5. William G. Honer
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  6. Ric M. Procyshyn
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Corresponding author

Correspondence to Ric M. Procyshyn.

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Sources of funding

Canadian Institutes of Health Research, the BC Mental Health and Substance Use Services, and Jack Bell Chair in Schizophrenia.

Conflict of interest

Dr. Procyshyn has been a member of the following advisory boards in the past 3 years: Janssen, Lundbeck, Otsuka, and Sunovion; a member of the following speaker’s bureaus in the past 3 years: AstraZeneca, Janssen, Lundbeck, Otsuka; and received grants from the Canadian Institutes of Health Research. Dr. Honer has received consulting fees or sat on paid advisory boards for MDH Consulting, In Silico (no honorarium), Novartis, Eli Lilly, Roche, Otsuka, and Lundbeck; received honoraria from Rush University, the Fraser, Vancouver Coastal, and Providence Health Authorities; and received grants from the Canadian Institutes of Health Research. Dr. Barr has received grants from Bristol-Myers Squibb and the Canadian Institutes of Health Research. Dr. Collier has received prize money from the SimCYP consortium, sat on paid advisory boards for the EPA (USA), and received grants from the National Institutes of Health. L.H.N. Lee and C. Choi declare that they have no conflicts of interest.

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Lee, L.H.N., Choi, C., Collier, A.C. et al. The Pharmacokinetics of Second-Generation Long-Acting Injectable Antipsychotics: Limitations of Monograph Values. CNS Drugs 29, 975–983 (2015). https://doi.org/10.1007/s40263-015-0295-2

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  • DOI: https://doi.org/10.1007/s40263-015-0295-2

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