The case concerns a 53-year-old man with pulmonary aspergillosis and tuberculosis treated simultaneously with voriconazole and rifapentine. Co-administration of rifapentine caused a significant decrease in voriconazole levels to 0.4 μg/ml (day 7), which represented a 90.7% reduction compared to the level of 4.3 μg/ml without rifapentine. After stopping rifapentine and increasing the dose of voriconazole to 300 mg intravenously every 12 hours, the level remained low for two more days (0.4 μg/ml on day 10). The level gradually increased to 3.0 μg/ml by day 14 and to 10.8 μg/ml by day 18, exceeding the therapeutic range. The case shows that rifapentine strongly reduces voriconazole levels and this effect persisted for more than a week after its discontinuation. Increasing the dose of voriconazole immediately after discontinuation of rifapentine has been shown to be inappropriate as it may later lead to excessively high levels and potential toxicity. Therapeutic monitoring of voriconazole should continue even after target levels are achieved due to the risk of supratherapeutic exposure.