Assessment of the Pharmacokinetic Profile of Tacrolimus Medications and Their Relation to Effectiveness and Safety in Liver Transplant Patients

The primary aim of the study is to assess tolerability of LCPT and graft function within the 24-month observational period. Other objectives include the assessment of the intraindividual variability of the TL and TDD, the incidence of BK and cytomegalovirus infections, the incidence of graft insufficiency and acute and chronic graft rejection. There are few real-life studies available on maintenance treatment regimens in liver transplant patients throughout Europe, and these only focus on the healthcare resources' consumption. There is a lack of data describing the effectiveness of different drugs and their combinations in early maintenance immunosuppression in the real-life setting. Even less data is available of ISU (immunosuppression) drugs combinations' metabolism and its relation to effectiveness and safety, measured in liver transplant patients.

Given the above considerations we planned this non-interventional study (NIS) to assess pharmacokinetic parameters of LCPT and other tacrolimus containing medications and their relation to efficacy and tolerability in hepatic allograft recipients in a real-life setting.

Inclusion criteria

• Patients ≥ 18 years of age
• Patients after liver- or simultaneous liver and kidney transplantation
• Having received a tacrolimus containing immunosuppressant therapeutic regimen at least for four weeks (induction therapy), and TL is within 5-20 ng/ml before inclusion
• Patients signed an informed consent form for use of their pseudonymised clinical data within the present non-interventional trial.

Exclusion criteria

• Participation in any clinical trial, 30 days prior to inclusion
• The patients received liver allograft more than 6 months before inclusion
• Hospitalisation due to infection, acute rejection, or graft disfunction 2 weeks prior to enrolment
• Chronic graft insufficiency in the patient's history
• Use of medications 2 weeks prior to enrolment, or the need for continuous use of medications that are known to significantly affect the pharmacokinetics of tacrolimus containing medications (as CYP3A4 inducers: rifampin, carbamazepine, phenobarbital, and phenytoin, or CYP3A4 inhibitors: erythromycin, ketoconazole, clarithromycin, and verapamil containing medication)
• Presence of the following comorbidities:

• Diseases affecting adherence to therapy (Chronic neurologic conditions, Psychiatric diseases)
• Diseases affecting drug absorption and metabolism (Inflammatory bowel disease, Chronic inflammatory diseases of bile ducts, Presence of ascites due to any disease)
• Patients on waiting list for re-transplantation