Original Title: Dosage plasmatique du linénolide

Authors' objectives: The Institut national d'excellence en santé et en services sociaux (INESSS) has received a request to include a new assay in the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the "Répertoire"), through the mechanism for evaluating new medical biology assays. The mandate is to assess the relevance of including linezolid in the Repertoire as part of Therapeutic Drug Monitoring (TDM). This is the second evaluation for this mandate. As this request includes new elements, the INESSS has re-evaluated the relevance of this assay from a provincial perspective.

Authors' results and conclusions: RESULTS (#1 SOCIO-CULTURAL DIMENSION): Internationally, there are a number of guidelines for the use of linezolid that are restricted to a particular country or healthcare facility, including Quebec, and which mention the relevance of linezolid dosing. In addition, learned societies and other international consensuses have taken a position on linezolid dosing. They have published recommendations on the usefulness of therapeutic follow-up and the individualization of linezolid treatment, particularly in critically ill patients and those suffering from renal or hepatic insufficiency. (#2 POPULATION DIMENSION): The desired therapeutic range for linezolid is relatively narrow, between 2 and 7 or 8 mg/L, depending on the references. Inter-individual variability in linezolid plasma concentrations may be observed in patients treated with a standard regimen. Significantly low concentrations can lead to treatment failure, while the opposite exposes the patient to serious toxicities, particularly when treatment is prolonged beyond 14 days. Although few linezolid assays are currently performed, the majority of requests for linezolid assays are made to the Centre hospitalier universitaire Sainte-Justine (CHUSJ) outside the Répertoire and come from various institutions. (#3 CLINICAL DIMENSION): According to the scientific data collected on clinical utility, the inter-individual variability observed in linezolid exposure is partially explained by age, body weight, and impaired renal function. Inter-individual variations in linezolid concentrations are associated with a risk of adverse events, such as thrombocytopenia, anemia or lactic acidosis, and consequent therapeutic failure. Therapeutic monitoring of linezolid reduces the occurrence of serious toxicities. Clinicians consulted indicated that, due to complicated medical situations such as documented infections with resistant bacteria, some patients may require a longer treatment regimen. They report that the occurrence of toxicities, notably hematological and neuropathic, such as peripheral or optic neuropathy, observed with prolonged linezolid use can only be adequately anticipated by plasma concentration measurements and complete blood count (CBC) results. The predicted response time of 24 to 48 hours has been described as clinically optimal. (#4 ORGANIZATIONAL DIMENSION): The HPLC-DAD (High-Performance Liquid Chromatography with Diode-Array Detection) method is available in Quebec in several laboratories to meet demand. However, excluding the CHUSJ laboratory, only one other laboratory has expressed interest in offering the test in the future. The clinicians consulted do not foresee an increase in the number of linezolid assays in the event of its inclusion in the Répertoire. (#5 ECONOMIC DIMENSION - EFFICACY): No studies evaluating the cost-effectiveness of linezolid dosing were found in the scientific literature. According to the clinicians consulted, adding linezolid dosing to the standard of care could optimize the current management of certain patients receiving this treatment, notably by ensuring its efficacy and limiting the sometimes-irreversible toxicities. However, quantifying the benefits that could have an impact on costs is fraught with uncertainty. Thus, the INESSS cannot rule on the efficacy of the linezolid assay. (#5.1 ECONOMIC DIMENSION - BUDGET IMPACT ANALYSIS): Based on the assumptions made, the introduction of the linezolid assay to the Repertoire could cost approximately $8.5 k for the first three years. It is estimated that 120 tests will be performed over this period. Sensitivity analyses show that the net impact of introducing the linezolid test to the Repertoire could vary from around $7 k to $12 k over three years.

Authors' recommendations: In light of the above findings based on the five dimensions of value evaluation, the INESSS recommends that the Minister introduce the linezolid plasma assay into the Répertoire. Linezolid dosing should only be used in certain populations to maximize its clinical relevance. Here are some examples: • Patients on long-term linezolid therapy (more than 10 days); • Altered pharmacokinetics due to body weight, age, renal, or hepatic impairment; • Suspected toxicity; • Drug interactions; • Suspected non-adherence to therapy. The analysis must meet the requirements of ISO 15189 if it is to be included in the Repertoire.

Authors' methods: The evaluation process included a review of the scientific literature, a search of the grey literature and consultations with clinicians, and other stakeholders. The methodology was designed around the five dimensions of the statement of principles of the INESSS framework for evaluating the value of interventions: socio-cultural, population-based, clinical, organizational, and economic. A review of the economic literature was conducted on the cost-effectiveness of linezolid dosing. A budgetary impact analysis was also conducted, considering the costs associated with the introduction of linezolid dosing in the Répertoire. Costs were projected over a three-year time frame from a healthcare system perspective. All the scientific, contextual, and experiential data were interpreted and synthesized in findings to guide the deliberative process of the Standing Deliberative Committee (SDC) - Diagnostic Approaches and Screening, with a view to making recommendations.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-plasmatique-du-linezolide.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-plasmatique-du-linezolide.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)