Abstract
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.
MeSH terms
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Adult
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Antifungal Agents / adverse effects
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Antifungal Agents / pharmacology*
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Antifungal Agents / therapeutic use
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Aspergillosis / prevention & control
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Candidiasis / prevention & control
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Cystic Fibrosis / drug therapy
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Cystic Fibrosis / prevention & control*
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Cytochrome P-450 CYP3A / metabolism
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Cytochrome P-450 CYP3A Inhibitors
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Drug Interactions
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Drug Monitoring
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Drug-Related Side Effects and Adverse Reactions
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Enzyme Inhibitors / pharmacology*
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Female
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Graft Rejection / prevention & control
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Humans
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Immunosuppressive Agents / adverse effects
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Immunosuppressive Agents / pharmacology*
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Itraconazole / pharmacology
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Lung Transplantation / immunology*
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Male
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Microbial Sensitivity Tests
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Mycoses / prevention & control*
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Prescriptions
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Pyrimidines / pharmacology
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Pyrimidines / therapeutic use
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Tacrolimus / pharmacology
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Tacrolimus / therapeutic use
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Triazoles / adverse effects
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Triazoles / pharmacology*
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Triazoles / therapeutic use
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Voriconazole
Substances
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Antifungal Agents
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Cytochrome P-450 CYP3A Inhibitors
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Enzyme Inhibitors
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Immunosuppressive Agents
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Pyrimidines
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Triazoles
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Itraconazole
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posaconazole
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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Voriconazole
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Tacrolimus