Outdated Product Labeling and Implications for Contemporary Standards of Care: The Example of Clozapine

23/10/2026

AI Summary

June 2025 clozapine package insert retains outdated recommendations such as rapid titration, twice daily initiation, and ignores patient factors; omits myocarditis guidance.
A PI does not define the standard of care and is inadmissible in malpractice cases without expert testimony, per case law review.
Clinicians should follow contemporary evidence-based practices, document rationales for PI deviations, and feel reassured when treating patients accordingly.

TL;DR (AI Generated)

However, that PI update retained many elements that are inconsistent with modern clozapine prescribing, including rapid titration, twice-daily dosing at the start of therapy, and titration without regard to patient factors (e.g., ancestry, sex and gender, or smoking status).

This discrepancy between the clozapine PI and evidence-based practices has caused clinicians to consider whether deviation from the PI presents a medicolegal risk and how to cope with outdated PI information for clozapine and other medications.

This article reviews the relative weight of different forms of medical evidence in establishing the standard of care, illustrates through case law that a PI does not define the standard of care and is inadmissible in malpractice litigation without expert testimony, and provides guidance for clinicians on how to navigate outdated, non-evidence-based PI recommendations.

Basic summary

Psychiatr Serv. 2026 Oct 22:appips20260173. doi: 10.1176/appi.ps.20260173. Online ahead of print.

ABSTRACT

Discontinuation of the U.S. Food and Drug Administration’s clozapine risk evaluation and mitigation strategy program led to a package insert (PI) revision in June 2025. However, that PI update retained many elements that are inconsistent with modern clozapine prescribing, including rapid titration, twice-daily dosing at the start of therapy, and titration without regard to patient factors (e.g., ancestry, sex and gender, or smoking status). The revision also provided no guidance on monitoring for myocarditis or mitigating the primary causes of mortality-pneumonia and ileus. This discrepancy between the clozapine PI and evidence-based practices has caused clinicians to consider whether deviation from the PI presents a medicolegal risk and how to cope with outdated PI information for clozapine and other medications. This article reviews the relative weight of different forms of medical evidence in establishing the standard of care, illustrates through case law that a PI does not define the standard of care and is inadmissible in malpractice litigation without expert testimony, and provides guidance for clinicians on how to navigate outdated, non-evidence-based PI recommendations. The information in this article should reassure clinicians that using modern evidence-based care-not archaic PI recommendations-is the optimal choice when treating patients.

PMID:42908070 | DOI:10.1176/appi.ps.20260173

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