Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis

Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of...

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Published in:International journal of antimicrobial agents Vol. 64; no. 4; p. 107302
Main Authors: Kuhlin, Johanna, Davies Forsman, Lina, Osman, Aisha, Skagerberg, Magdalena, Jonsson, Jerker, Groenheit, Ramona, Mansjö, Mikael, Werngren, Jim, Alffenaar, Jan-Willem, Schön, Thomas, Bruchfeld, Judith
Format: Journal Article
Language:English
Published: Netherlands Elsevier Ltd 01.10.2024
Subjects:
adverse drug reactions
Anaemia
Drug concentrations
Infectious Disease
Leukopenia
Linezolid
MDR-TB
Peripheral neuropathy
Thrombocytopenia
Linezolid
Thrombocytopenia
CTCAE
MGIT
Leukopenia
Anaemia
MIC
MDR-TB
HR
Peripheral neuropathy
ADR
AUC
adverse drug reactions
Drug concentrations
BMI
WHO
area under the concentration time-curve
adverse drug reaction
Common Terminology Criteria for Adverse Events
World Health Organization
body mass index
multidrug-resistant tuberculosis
minimum inhibitory concentration
Mycobacterial Growth Indicator Tube
hazard ratio
leukopenia
linezolid
anaemia
thrombocytopenia
drug concentrations
peripheral neuropathy
ISSN:0924-8579, 1872-7913, 1872-7913
Online Access:Get full text
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Summary:Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992–2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). Of all participants (n = 132), 43.2% were female and the median age 28 y. The median linezolid treatment was 6.5 months (IQR 3.0–12.7) with a median daily dose of 9.6 mg/kg/d. Any ADR was seen in 58.3% (n = 77) of participants, with 35.6% having peripheral neuropathy (n = 47), 27.3% anaemia (n = 36), 22.0% leukopenia (n = 36) while 6.1% (n = 8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1–5.9) and 8.3 months (6.2–10.7) for optic neuritis. A >2.0 mg/L trough concentration (n = 40) was associated with anaemia (P = 0.0038) and thrombocytopenia (P = 0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/d was associated with time to peripheral neuropathy (HR 2.89, 95% CI 1.08–7.74, P = 0.035), anaemia (HR 6.62, 95% CI 2.22–19.8, P = 0.001) and leukopenia (HR 5.23, 95% CI 1.48–18.5, P = 0.010). Linezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity. [Display omitted]
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ISSN:0924-8579
1872-7913
1872-7913
DOI:10.1016/j.ijantimicag.2024.107302