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Posaconazole represents an antifungal extended-spectrum triazole whose absolute bioavailability following oral drug administration is considerably variable. Special conditions including increased gastric pH values, malabsorption syndrome, diarrhoea, intake on an empty stomach and some concomitantly administered potent enzyme-inducing drugs may contribute to lower drug plasma levels than expected. As a consequence, establishment of Therapeutic Drug Monitoring (TDM) has been proposed to be beneficial in patients receiving antifungal prophylaxis or therapy with posaconazole. Based on its considerable CYP3A inhibiting potency, posaconazole may significantly increase plasma concentrations of concomitantly applied drugs which undergo an extensive first-pass effect through gut and liver. More intensified posaconazole TDM may help to estimate the extent of drug interaction more accurately.