Hematological toxicities associated with linezolid therapy in adults: key findings and clinical considerations

ABSTRACT

Introduction

Linezolid can cause serious adverse effects including thrombocytopenia and anemia. Here, we focus specifically on linezolid-related hematological toxicity in adult patients requiring prolonged drug treatment.

Areas covered

We review the available evidence on the likelihood of hematological toxicity in adult patients treated with linezolid, with a focus on the main risk factors and strategies to prevent this adverse event. A MEDLINE PubMed search for articles published from January 2000 to May 2022 was completed matching the terms linezolid, hematology, hematological toxicity, anemia, and thrombocytopenia. Moreover, additional studies were identified from the reference lists of retrieved articles.

Expert opinion

Thrombocytopenia is the major concern with administration of linezolid for Gram-positive infections, whereas anemia is more common in patients with tuberculosis. The important clinical risk factors for the development of linezolid-related thrombocytopenia are aging, renal dysfunction, low baseline platelet count, duration of treatment, and linezolid plasma trough concentrations >8 mg/L. Patients receiving linezolid for extended periods of time or patient populations with increased risk of altered drug pharmacokinetics would benefit from therapeutic drug monitoring or from the availability of toxico-dynamic predictive models to optimize linezolid dosing.

KEYWORDS:

• Linezolid
• hematological toxicity
• anemia
• thrombocytopenia
• therapeutic drug monitoring

Article highlights

• Patients requiring prolonged linezolid treatment (i.e. more than 10 days) are at risk of developing drug-related hematological toxicity, often resulting in premature linezolid discontinuation.

• Risk factors for the development of linezolid-related myelosuppression include aging, renal dysfunction, low baseline platelet count, and linezolid plasma trough concentrations > 8 mg/L.

• The risk of developing linezolid-related hematological toxicity could be minimized in clinical practice by dose optimization (reduction) guided by therapeutic drug monitoring

• The heterogeneity in diseases, linezolid dosing, study methods, and definitions of toxicity undoubtedly represent important limitations for the establishment of a causal relationship between linezolid use and development of hematological toxicity.

• A multidisciplinary team involving physicians, pharmacists, clinical pharmacologists, and health-care professionals recognizing risk factors of linezolid-associated hematological toxicity is warranted.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.