Research advances and clinical management of drug interactions between voriconazole and antituberculosis agents
- 1Department of Pharmacy, Quanzhou First Hospital Affiliated to Fujian Medical University
- 2College of Pharmacy, Fujian Medical University
Abstract
Background: When tuberculosis is complicated by fungal infection, voriconazole and antituberculosis drugs may need to be used in combination, and drug interactions can affect efficacy and safety.
Methods: This structured narrative review used a systematic literature search of PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure (CNKI) from database inception to May 2026, together with predefined eligibility criteria and evidence stratification. Clinical pharmacokinetic, therapeutic drug monitoring (TDM), observational, case-report, and case-series studies were eligible as the primary evidence base. Relevant in vitro studies were reviewed only as mechanistic, hypothesis-generating evidence and were not treated as primary clinical evidence. Because of substantial heterogeneity in study design, populations, interventions, pharmacokinetic endpoints, and reporting completeness, the findings were synthesized narratively rather than quantitatively. The direction and potential clinical significance of interactions and key considerations for TDM were summarized by evidence type.
Results: A total of 2,198 records were identified, and 17 primary clinical studies were included. Most were case reports or small retrospective studies, with limited paired antituberculosis-drug exposure data and clinical outcomes; generalizability is therefore limited. Existing clinical pharmacokinetic evidence is concentrated on rifamycins. Rifampicin markedly reduces voriconazole exposure and its induction may persist after discontinuation, so coadministration should be avoided. Rifapentine can also substantially lower voriconazole concentrations, with interindividual variability in the offset of induction; dose adjustment and re-initiation after withdrawal require serial TDM. Rifabutin has a bidirectional interaction: it can reduce voriconazole exposure, while voriconazole may increase exposure to rifabutin and its active metabolite. Current U.S. voriconazole labeling lists rifabutin coadministration as contraindicated, and rare off-label case experience does not establish it as a safe alternative. For isoniazid, ethambutol, linezolid, and other non-rifamycin agents, available evidence is mechanistic or hypothesis-generating and does not establish causal interactions or justify empirical voriconazole dose adjustment.
Conclusion: Management should prioritize avoidance of voriconazole coadministration with rifampicin and rifabutin in accordance with current labeling, and avoidance of rifapentine where feasible. If rifapentine exposure cannot be avoided or has recently stopped, serial TDM should guide voriconazole dosing. For non-rifamycin antituberculosis drugs, monitoring should be matched to the suspected risk (exposure variability, QT prolongation, hepatotoxicity, or optic, neurologic, or hematologic toxicity) rather than based on unvalidated empirical dose changes.
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BibTeX
@article{fu2026research,
title = {{Research advances and clinical management of drug interactions between voriconazole and antituberculosis agents}},
author = {Yijie Fu and Zhiqiang Lin},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1962108},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1962108/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Research advances and clinical management of drug interactions between voriconazole and antituberculosis agents
AU - Yijie Fu
AU - Zhiqiang Lin
PY - 2026
DA - 2026/10/21
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1962108
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1962108/full
AB - Background: When tuberculosis is complicated by fungal infection, voriconazole and antituberculosis drugs may need to be used in combination, and drug interactions can affect efficacy and safety. Methods: This structured narrative review used a systematic literature search of PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure (CNKI) from database inception to May 2026, together with predefined eligibility criteria and evidence stratification. Clinical pharmacokinetic, therapeutic drug monitoring (TDM), observational, case-report, and case-series studies were eligible as the primary evidence base. Relevant in vitro studies were reviewed only as mechanistic, hypothesis-generating evidence and were not treated as primary clinical evidence. Because of substantial heterogeneity in study design, populations, interventions, pharmacokinetic endpoints, and reporting completeness, the findings were synthesized narratively rather than quantitatively. The direction and potential clinical significance of interactions and key considerations for TDM were summarized by evidence type. Results: A total of 2,198 records were identified, and 17 primary clinical studies were included. Most were case reports or small retrospective studies, with limited paired antituberculosis-drug exposure data and clinical outcomes; generalizability is therefore limited. Existing clinical pharmacokinetic evidence is concentrated on rifamycins. Rifampicin markedly reduces voriconazole exposure and its induction may persist after discontinuation, so coadministration should be avoided. Rifapentine can also substantially lower voriconazole concentrations, with interindividual variability in the offset of induction; dose adjustment and re-initiation after withdrawal require serial TDM. Rifabutin has a bidirectional interaction: it can reduce voriconazole exposure, while voriconazole may increase exposure to rifabutin and its active metabolite. Current U.S. voriconazole labeling lists rifabutin coadministration as contraindicated, and rare off-label case experience does not establish it as a safe alternative. For isoniazid, ethambutol, linezolid, and other non-rifamycin agents, available evidence is mechanistic or hypothesis-generating and does not establish causal interactions or justify empirical voriconazole dose adjustment. Conclusion: Management should prioritize avoidance of voriconazole coadministration with rifampicin and rifabutin in accordance with current labeling, and avoidance of rifapentine where feasible. If rifapentine exposure cannot be avoided or has recently stopped, serial TDM should guide voriconazole dosing. For non-rifamycin antituberculosis drugs, monitoring should be matched to the suspected risk (exposure variability, QT prolongation, hepatotoxicity, or optic, neurologic, or hematologic toxicity) rather than based on unvalidated empirical dose changes.
SN - 1663-9812
ER -