Making sense of posaconazole therapeutic drug monitoring: a practical approach

Therapeutic drug monitoring (TDM) may be an important adjunct to optimizing the use of posaconazole.

Limited clinical studies suggest that an exposure-response relationship for posaconazole exists for the treatment of established invasive fungal diseases (IFDs), with emerging but less compelling data supporting its role in prophylaxis. The high prevalence of subtherapeutic levels has not translated to high prophylactic failure rates perhaps because of preferential uptake by effector cells important in the front-line defence against Aspergillus species. Nevertheless, TDM would appear prudent in patients deemed at highest risk for IFD with correction of patient modifiable factors and attention to drug administration important in optimizing drug exposure. TDM performed within a few days after commencing posaconazole may be predictive of steady-state levels, thus minimizing the delay in obtaining results in addition to identifying a subset of patients who may remain persistently subtherapeutic and also resistant to dose-escalation. Trough levels may be supplanted by untimed levels at steady state, thereby expanding the practicalities of TDM. We propose that TDM becomes one of the several measures in an integrated approach to IFD prevention combining screening of high-risk haematology patients for invasive aspergillosis at presentation, together with prospective surveillance for IFD, explicit criteria for switching to an alternative prophylactic agent and adherence to infection control practices.

Growing evidence supports the value of TDM for posaconazole to identify patients who may benefit from correction of modifiable factors impacting bioavailability, dosage adjustment or switch to an alternative agent.