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A Disproportionality Analysis of Drug–Drug Interactions of Tizanidine and CYP1A2 Inhibitors from the FDA Adverse Event Reporting System (FAERS)

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A Letter to the Editor to this article was published on 12 October 2022

Abstract

Introduction

Tizanidine is primarily metabolized via cytochrome P450 (CYP) 1A2 and therefore medications that inhibit the enzyme will affect the clearance of tizanidine, leading to increased plasma concentrations of tizanidine and potentially serious adverse events.

Objectives

Our aim was to study the occurrence of adverse events reported in the FDA Adverse Event Reporting System (FAERS) involving the combination of tizanidine and drugs that inhibit the metabolic activity of CYP1A2.

Methods

A disproportionality analysis of FAERS reports from 2004 quarter 1 through 2020 quarter 3 was conducted to calculate the reporting odds ratio (ROR) of reports mentioning tizanidine in a suspect or interacting role or having any role, a CYP1A2 inhibitor, and the following adverse events: hypotension, bradycardia, syncope, shock, cardiorespiratory arrest, and fall or fracture.

Results

A total of 89 reports were identified mentioning tizanidine, at least one CYP1A2 inhibitor, and one of the adverse events of interest. More than half of the reports identified tizanidine as having a suspect or interacting role (n = 59, 66.3%), and the reports more frequently involved women (n = 58, 65.1%). The median age was 56.1 years (standard deviation 17.1). Some of the important safety signals included interactions between tizanidine in a suspect or interacting role and ciprofloxacin (ROR for hypotension 28.1, 95% confidence interval [CI] 19.2–41.2) or fluvoxamine (ROR for hypotension 36.9, 95% CI 13.1–103.4), and also when reported in “any role” with ciprofloxacin (ROR for hypotension 6.3, 95% CI 4.7–8.5), fluvoxamine (ROR for hypotension 11.4, 95% CI 4.5–28.8), and zafirlukast (ROR for falls 16.0, 95% CI 6.1–42.1).

Conclusions

Reports involving tizanidine and a CYP1A2 inhibitor have higher odds of reporting hypotension. This study suggests that concurrent use of tizanidine with CYP1A2 inhibitors may lead to serious health consequences associated with low blood pressure such as falls and fractures.

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Authors and Affiliations

  1. Department of Pharmacy Practice, College of Pharmacy, Mercer University, Atlanta, GA, USA

    Lorenzo Villa-Zapata

  2. Department of Pharmacotherapy, College of Pharmacy, University of Utah, 30 S 2000 E, Salt Lake City, UT, 84112, USA

    Ainhoa Gómez-Lumbreras, Malinda S. Tan & Daniel C. Malone

  3. Department of Pharmacy, School of Pharmacy, University of Washington, Seattle, WA, USA

    John Horn

  4. Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA

    Richard D. Boyce

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  1. Lorenzo Villa-Zapata
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Corresponding author

Correspondence to Daniel C. Malone.

Ethics declarations

Funding

This study was funded by the Agency for Healthcare Research and Quality, grant number R01HS025984.

Conflict of interest

Lorenzo Villa-Zapata, Ainhoa Gómez-Lumbreras, John Horn, Malinda S. Tan, Richard D. Boyce, and Daniel C. Malone report no conflicts of interest.

Ethical approval

Ethic approval was not sought from the Institutional Review Board as the study only involved the analysis of data obtained from a public database. Informed consent to participate was not applicable.

Consent to participate/publication

Not applicable.

Availability of data and material

The source data for this study are publicly available. Analytical datasets are available from the corresponding author on reasonable request.

Code availability

Computer code used in this analysis is available from the authors on request.

Authors’ contribution

LVZ participated in developing the study protocol and research design, analyzed data, and contributed to interpretation the data. AGL has participated developing the study protocol and research design, interpretation of the data and drafted the first manuscript. JH participated in the research protocol, interpretation of the data and edited the manuscript. MT participated in developing the research design and interpretation of the results. RB participated in the study design, conducted the data extraction and data analysis. DCM supervised the study and drafted the study protocol and research design, guided the analysis of the data, provided interpretation as well as edited the manuscript. All authors have reviewed and approved the manuscript.

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Villa-Zapata, L., Gómez-Lumbreras, A., Horn, J. et al. A Disproportionality Analysis of Drug–Drug Interactions of Tizanidine and CYP1A2 Inhibitors from the FDA Adverse Event Reporting System (FAERS). Drug Saf 45, 863–871 (2022). https://doi.org/10.1007/s40264-022-01200-4

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