Management of the combination of tacrolimus with azoles: effect of tacrolimus formulation on drug-drug interaction magnitude

Recruiting

• Conditions: 10017528; Mycoses due to opportunistic pathogens; fungal infection in patients with immune deficiencies who would otherwise not be infected

• Registration Number: NL-OMON54925
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

- Lung, kidney, pancreas or heart transplant recipient
- Age >18 years
- Stable use of tacrolimus formulations Prograf/generic tacrolimus/Envarsus
- Indication for antifungal therapy with voriconazole
- Written informed consent

Exclusion Criteria

- Administration of mTOR inhibitors, cyclosporine or quadruple immunosuppression
- Concomitant use of drugs that have a pharmacokinetic interaction with
tacrolimus
- Acute liver- or intestinal function impairment
- Pregnancy

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess whether IR-Tac and ER-Tac exhibit a different magnitude of drug-drug<br /><br>interaction after co-administration of voriconazole in lung, kidney, pancreas<br /><br>or heart transplant recipients.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To describe all relevant PK parameters for IR-Tac and ER-Tac, their<br /><br>fold-change after azole initiation and the relevant azole PK parameters (which<br /><br>are: Cmax, dose-adjusted Cmax, Cmin, dose-adjusted Cmin, Tmax, t1/2).<br /><br>- To describe whether pharmacogenetic genotype and inflammatory markers have an<br /><br>additional influence on tacrolimus and azole pharmacokinetics<br /><br>- To investigate whether and with what extend the interaction diminishes over<br /><br>time after discontinuation of the interacting drug, as measured with Cmin/dose<br /><br>ratio<br /><br>- To evaluate how tacrolimus dose should be adjusted at start and<br /><br>discontinuation of the voriconazole, and how many dose adjustments are needed<br /><br>for both formulations </p><br>