Safe management of tacrolimus together with posaconazole in lung transplant patients with cystic fibrosis.
Oral posaconazole (PSZ), an azole antifungal drug, was recently introduced for the treatment of invasive fungal infections. The prescription of PSZ together with the immunosuppressant tacrolimus (TRL) was evaluated in 14 lung transplant patients with cystic fibrosis. PSZ inhibited CYP3A4 TRL metabolism, resulting in a decrease of TRL dose by a factor of 3, with tapering to a mean of 2 mg/d. Previous studies with itraconazole and voriconazole showed that TRL dose could be decreased by factors of 5 and 4, respectively. Joint therapeutic drug monitoring of TRL and PSZ was carried out to investigate the high risk of interindividual variability associated with this coprescription in such patients.
Hôpital Européen G Pompidou, Paris 75015, France.
Maud
M
Berge
Patrick
P
Chevalier
Mohammed
M
Benammar
Romain
R
Guillemain
Catherine
C
Amrein
Sandrine
S
Lefeuvre
Véronique
V
Boussaud
Eliane M
EM
Billaud
D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001228:Aspergillosis / Q000517:prevention & control; D002177:Candidiasis / Q000517:prevention & control; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000517:prevention & control*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D016903:Drug Monitoring; D064420:Drug-Related Side Effects and Adverse Reactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D017964:Itraconazole / Q000494:pharmacology; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008826:Microbial Sensitivity Tests; D009181:Mycoses / Q000517:prevention & control*; D055656:Prescriptions; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D065819:Voriconazole; D016559:Tacrolimus