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Concomitant use of ...
Concomitant use of isavuconazole and CYP3A4/5 inducers : Where pharmacogenetics meets pharmacokinetics
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- Van Daele, Ruth (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Univ Hosp Leuven, Dept Pharm, Leuven, Belgium.
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- Debaveye, Yves (author)
- Univ Hosp Leuven, Intens Care Unit, Leuven, Belgium.;Katholieke Univ Leuven, Dept Cellular & Mol Med, Leuven, Belgium.
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- Vos, Robin (author)
- Univ Hosp Leuven, Resp Dis, Clin Dept Lab Med, Leuven, Belgium.;Katholieke Univ Leuven, BREATHE, Chrometa Dept, Leuven, Belgium.
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- Van Bleyenbergh, Pascal (author)
- Univ Hosp Leuven, Resp Dis, Clin Dept Lab Med, Leuven, Belgium.
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- Bruggemann, Roger J. (author)
- Radboudumc, Dept Pharm, Nijmegen, Netherlands.;Radboudumc, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboudumc, Ctr Infect Dis, Nijmegen, Netherlands.
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- Dreesen, Erwin (author)
- Uppsala universitet,Institutionen för farmaci,Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.
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- Elkayal, Omar (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.
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- Guchelaar, Henk-Jan (author)
- Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Leiden, Netherlands.
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- Vermeersch, Pieter (author)
- Univ Hosp Leuven, Clin Dept Lab Med, Leuven, Belgium.;Univ Hosp Leuven, Natl Reference Ctr Mycosis, Excellence Ctr Med Mycol ECMM, Leuven, Belgium.
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- Lagrou, Katrien (author)
- Univ Hosp Leuven, Clin Dept Lab Med, Leuven, Belgium.;Univ Hosp Leuven, Natl Reference Ctr Mycosis, Excellence Ctr Med Mycol ECMM, Leuven, Belgium.;Katholieke Univ Leuven, Dept Microbiol Immunol & Transplantat, Leuven, Belgium.
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- Spriet, Isabel (author)
- Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium.;Univ Hosp Leuven, Dept Pharm, Leuven, Belgium.
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Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Leuven, Belgium;Univ Hosp Leuven, Dept Pharm, Leuven, Belgium. Univ Hosp Leuven, Intens Care Unit, Leuven, Belgium.;Katholieke Univ Leuven, Dept Cellular & Mol Med, Leuven, Belgium. (creator_code:org_t)
- 2021-05-19
- 2021
- English.
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In: Mycoses. - : John Wiley & Sons. - 0933-7407 .- 1439-0507. ; 64:9, s. 1111-1116
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Background Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolised by CYP3A4 and CYP3A5, and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450 inducers is contraindicated, although it is known that some CYP450 inducers are less potent in comparison with rifampin. Objectives We aim to document exposure to isavuconazole in patients concomitantly treated with a CYP450 inducer that is less potent compared to rifampin. Moreover, although it is well known that CYP3A enzymes are important for the metabolism of isavuconazole, this induction effect has never been studied in combination with the patient's CYP3A genotype. Patients We report three patients treated with both isavuconazole and a CYP3A inducer that is less potent compared to rifampin (rifabutin or phenobarbital), in whom we determined isavuconazole concentrations. Results These cases suggest that the CYP3A4/5 genotype is an important determinant for isavuconazole exposure and that it might also influence the CYP450 induction interaction. Conclusions CYP3A inducers that are less potent compared to rifampin, may be combined with isavuconazole in patients with loss of CYP3A5 activity (CYP3A5*3/*3). Therapeutic drug monitoring is recommended during this combination. However, low-isavuconazole exposure was observed in the extensive metaboliser with CYP3A4*1/*1 and CYP3A5*1/*3 alleles.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- CYP450 induction
- exposure
- genotyping
- isavuconazole
- phenobarbital
- rifabutin
Publication and Content Type
- ref (subject category)
- art (subject category)
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Mycoses
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- By the author/editor
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Van Daele, Ruth
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Debaveye, Yves
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Vos, Robin
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Van Bleyenbergh, ...
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Bruggemann, Roge ...
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Dreesen, Erwin
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Elkayal, Omar
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Guchelaar, Henk- ...
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Vermeersch, Piet ...
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Lagrou, Katrien
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Spriet, Isabel
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- MEDICAL AND HEALTH SCIENCES
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and Basic Medicine
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Mycoses
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Uppsala University