A Drug Safety Concept (I) to Avoid Polypharmacy Risks in Transplantation by Individual Pharmacotherapy Management in Therapeutic Drug Monitoring of Immunosuppressants

Abstract

For several, also vital medications, such as immunosuppressants in solid organ and hematopoietic stem cell transplantation, therapeutic drug monitoring (TDM) remains the only strategy for fine-tuning the dosage to the individual patient. Especially in severe clinical complications, the intraindividual condition of the patient changes abruptly, and in addition, drug-drug interactions (DDIs) can significantly impact exposure, due to concomitant medication alterations. Therefore, a single TDM value can hardly be the sole basis for optimal timely dose adjustment. Moreover, every intraindividually varying situation that affects the drug exposure needs synoptic consideration for the earliest adjustment. To place the TDM value in the context of the patient's most detailed current condition and concomitant medications, the Individual Pharmacotherapy Management (IPM) was implemented in the posttransplant TDM of calcineurin inhibitors assessed by the in-house laboratory. The first strategic pillar are the defined patient scores from the electronic patient record. In this synopsis, the Summaries of Product Characteristics (SmPCs) of each drug from the updated medication list are reconciled for contraindication, dosing, adverse drug reactions (ADRs), and DDIs, accounting for defined medication scores as a second pillar. In parallel, IPM documents the resulting review of each TDM value chronologically in a separate electronic Excel file throughout each patient's transplant course. This longitudinal overview provides a further source of information at a glance. Thus, the applied two-arm concept of TDM and IPM ensures an individually tailored immunosuppression in the severely susceptible early phase of transplantation through digital interdisciplinary networking, with instructive and educative recommendations to the attending physicians in real-time. This concept of contextualizing a TDM value to the precise patient's condition and comedication was established at Halle University Hospital to ensure patient, graft, and drug safety.

Keywords: adverse drug reactions (ADRs); calcineurin inhibitors; drug elimination capacities; drug safety; drug-drug interactions (DDIs); electronic health record (EHR); electronic patient record; graft safety; immunosuppression; medication review; patient safety; polypharmacy; therapeutic drug monitoring (TDM); transplantation.

Figure 1

Comprehensive, reproducible IPM based on the electronic patient record. * IPM (applied patient and medication scores) based on the electronic hospital patient records at Halle University Hospital. This was conceptualized, implemented, and practiced by Wolf, MD, Head of Pharmacotherapy Management Department, specialist in internal medicine, with expertise in clinical pharmacology and transplantation, and performed > 59,700 individual IPM medication reviews.

Figure 2

The context of appropriate TDM assessment and subsequent adjustment: (a) The individual circuits affect each other. Therefore, interference monitoring is required. (b) Optimization of the TDM value by continuous synoptic contribution and adaptation to confounding risks from varying current patient conditions and altering comedications through simultaneous IPM in real-time. * IPM scores: see Figure 1.

Figure 3

Flowchart of the routinely contextualized TDM of immunosuppressants with the IPM concept at Halle University Hospital.