Question
How frequent is linezolid (Zyvox)-associated thrombocytopenia?
Answer
Thrombocytopenia, a condition characterized by low platelet count, has been associated with the use of certain antibiotics, including linezolid. Linezolid, a member of the oxazolidinone class of antibiotics, is a versatile antibiotic, coming in an oral and IV formulation and retaining activity to many gram-positive bacteria, including MRSA and VRE. Less often recognized, linezolid plays a role in the treatment of both tuberculosis and non-tuberculosis mycobacteria, where treatment durations are months rather than weeks. While linezolid is generally well-tolerated, the package insert warns of reversible myelosuppression after two weeks of use. The literature describes in patients receiving linezolid for at least 5 days, an incidence of new-onset thrombocytopenia associated with linezolid of about 18%.
Studies indicate that thrombocytopenia can occur with linezolid, but the frequency of this adverse effect depends on a variety of risk factors. The risk appears to be more pronounced in certain patient populations and conditions. Linezolid-induced thrombocytopenia incidence and risk factors are described in Zhang et al’s systematic review and meta-analysis. From their 40 articles, they identified a combined incidence of thrombocytopenia of 37%. Risk factors identified include advanced age, body mass index (lower BMI but not a lower weight), concurrent renal impairment or liver disease, longer treatment duration, renal replacement therapy and admission to the intensive care unit. Additionally, coadministration with fluoroquinolones, carbapenems, heparin and aspirin were found to be positively associated with linezolid-induced thrombocytopenia .
Prolonged use of linezolid has been identified as a factor that may increase the likelihood of developing thrombocytopenia. Senneville and colleagues describe their experience using linezolid for osteomyelitis. In their retrospective review, they found of 66 patients who received linezolid for >4 weeks because of chronic osteomyelitis, the median time from starting linezolid to anemia onset was 7.3 weeks (range 4-12 weeks) and occurred in 21 patients (31.8%) for which 16 (24.2%) required blood transfusions.
Linezolid is an appealing alternative to vancomycin when MRSA is suspected, since routine therapeutic drug monitoring, less fluid volume and nephrotoxicity are benefits to linezolid. Al-Harbi and colleagues note in their retrospective cohort of patients who received at least 5 days of either vancomycin or linezolid, significantly more thrombocytopenia when linezolid was deployed. The average duration of treatment to onset of severe thrombocytopenia in the linezolid group was 14 +/- 9.3 days compared with 8.5 +/- 6.9 days in the vancomycin group. Logistic regression analysis displayed patients receiving linezolid had roughly four times higher risk of thrombocytopenia (OR 4.39; 95% CI 2.38–8.08) and had a 3.8 times higher risk of having a platelet count < 100,000/µl (OR 3.77; 95% CI 1.55–9.17) compared to the vancomycin group.
Renal dysfunction is a significant factor that may contribute to an increased risk of thrombocytopenia in patients taking linezolid. Linezolid and its metabolites are primarily excreted through the kidneys, and impaired renal function can lead to higher drug concentrations in the bloodstream, potentially affecting platelet counts. As such, healthcare providers should exercise caution when prescribing linezolid to individuals with renal impairment. While the package insert does not state to adjust in renal impairment, post marketing data suggest it may be warranted.
In conclusion, while thrombocytopenia associated with linezolid is a recognized adverse effect, its frequency is relatively low and more likely with increased exposure. That noted, healthcare providers should be vigilant to beware it, particularly when considering prolonged use, in patients with renal dysfunction, and those with smaller body weights. Monitoring platelet counts and adjusting treatment plans accordingly can help mitigate the risk of this side effect and ensure the safe and effective use of linezolid in clinical practice.
ANSWERED BY
Hunter O. Rondeau, Pharm.D. – May 2024
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The ID PharmD Q&A pages attempt to answer common pharmacy questions by providing the perspective and opinion of a trained expert with knowledge relevant to the question. That noted, these answers are not provided as all-inclusive comprehensive responses. This is not provided for direct patient care purposes.
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