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Daily dosing of tacrolimus in patients treated with HIV-1 therapy containing a ritonavir-boosted protease inhibitor or raltegravir

Objectives The number of HIV-infected patients receiving orthotopic liver transplantation (OLTX) is increasing. One major challenge is the severe drug–drug interactions between immunosuppressive drugs such as tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The introduction of ralte...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2010-05, Vol.65 (5), p.999-1004
Main Authors: Bickel, Markus, Anadol, Evrim, Vogel, Martin, Hofmann, Wolf Peter, von Hentig, Nils, Kuetscher, Johannes, Kurowski, Michael, Moench, Christian, Lennemann, Tessa, Lutz, Thomas, Bechstein, Wolf Otto, Brodt, Hans Reinhard, Rockstroh, Jürgen
Format: Article
Language:English
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Summary:Objectives The number of HIV-infected patients receiving orthotopic liver transplantation (OLTX) is increasing. One major challenge is the severe drug–drug interactions between immunosuppressive drugs such as tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The introduction of raltegravir, which is not metabolized by the cytochrome system, may allow concomitant treatment without dose adaptation. Patients and methods We conducted a retrospective analysis of HIV-1-infected patients receiving tacrolimus concomitantly with different HIV therapies, including 12 h pharmacokinetic assessment of drug levels. Results Three OLTX patients received a ritonavir-boosted PI therapy when tacrolimus was added at very low doses of 0.06, 0.03 and 0.08 mg daily. Median tacrolimus blood levels were 6.6, 3.0 and 7.9 ng/mL over a follow-up period of 8, 22 and 33 months, respectively. In two other patients (one after OLTX and one with Crohn's disease), a raltegravir-based HIV therapy was started while patients received 1 or 2 mg of tacrolimus twice daily. No tacrolimus dose adjustment was necessary and drug levels remained unchanged. Conclusions Decreasing the dose of tacrolimus to 0.03–0.08 mg daily in patients with concomitant boosted PI therapy resulted in stable tacrolimus blood levels without alteration of PI drug levels. Concomitant use of raltegravir and tacrolimus revealed no clinically relevant drug interaction.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkq054