Effect of Itraconazole and Its Metabolite Hydroxyitraconazole on the Blood Concentrations of Cyclosporine and Tacrolimus in Lung Transplant Recipients

Matsuda, Yudai; Nakagawa, Shoichi; Yano, Ikuko; Masuda, Satohiro; Imai, Satoshi; Yonezawa, Atsushi; Yamamoto, Takashi; Sugimoto, Mitsuhiro; Tsuda, Masahiro; Tsuzuki, Tetsunori; Omura, Tomohiro; Nakagawa, Takayuki; Chen‐Yoshikawa, Toyofumi F.; Nagao, Miki; Date, Hiroshi; Matsubara, Kazuo

doi:10.1248/bpb.b21-00738

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…Another study on drug interactions with azole antifungal agents concluded that, when starting azole therapy, a pre-emptive dosage reduction of immunosuppressive agents (cyclosporine, tacrolimus, or sirolimus) should be strongly considered [17]. Tis fnding is consistent with the results of many studies [33][34][35][36][37]. However, some studies do not recommend prereduction of the CsA dose prior to co-administration.…”

Section: Discussionmentioning

confidence: 68%

Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia

Tian,

Song,

Qiao

et al. 2024

Journal of Clinical Pharmacy and Therapeutics

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Objectives. This study aimed to investigate the effects of different triazole antifungal agents on the blood concentration and dosage of cyclosporine (CsA) in patients with aplastic anaemia (AA). Methods. This retrospective study enrolled AA patients who received CsA and triazole antifungal agents simultaneously between January 2018 and December 2022. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) co-administration with and without azoles was compared. The effects of different triazole antifungal agents on blood concentrations and dosages of CsA were analysed. Results. The mean C/D ratio of CsA increased 1.97 times when co-administered with posaconazole (POS), while the mean C/D ratio of CsA increased 1.76 times when co-administered with fluconazole (FCZ). Compared with CsA monotherapy, there was a significant difference in CsA concentrations among patients with azoles (P<0.05). The mean dose of CsA decreased was 0.26 (−0.25—1.05) mg/kg/day and 0.18 (−0.50—0.69) mg/kg/day when co-administered with POS and FCZ, respectively. There is a wide interindividual variability in the magnitude of drug interaction between azoles and CsA. Conclusions. Although azoles increased CsA concentration, a wide individual variability was found in the patients with CsA C/D ratio. Therefore, the CsA dose should be adjusted by closely monitoring the blood levels of CsA co-administered with triazole antifungal agents. In addition, we observed that POS had a greater effect on the blood concentration of CsA than FCZ. When adjusting the dose of CsA in clinical practice, the blood concentration of CsA and the type of co-administered triazole antifungal agents should be considered.

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Section: Discussionmentioning

confidence: 68%

Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia

Tian,

Song,

Qiao

et al. 2024

Journal of Clinical Pharmacy and Therapeutics

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“…In humans, like in dogs, interactions between ciclosporin and itraconazole, resulting from inhibition of cytochrome P450 (CYP3A), allow the dose of ciclosporin to be reduced when the two molecules are combined. 6,20–22 Such interaction is not reported in cats; nevertheless, in a previous study, ketoconazole increased the concentration of ciclosporin in the blood about two-fold after ciclosporin was administered, 23 suggesting that the same applies to itraconazole. 22…”

Section: Discussionmentioning

confidence: 91%

Multifocal cutaneous phaeohyphomycosis caused by Exophiala spinifera with clinical resolution in an immunocompromised cat

Kondratjeva

Pressanti

Reynolds

et al. 2023

Journal of Feline Medicine and Surgery Open Reports

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Case summary A 3-year-old neutered domestic shorthair cat with a long history of idiopathic immune-mediated haemolytic anaemia and thrombocytopenia treated with ciclosporin and prednisolone was referred 2 months after the appearance of nodular dermatitis. A single pigmented nodule was present in the lateral carpal region of the right foreleg. The lesion was 7 mm in diameter, non-exudative and cutaneous to subcutaneous. Fine-needle aspiration of the mass revealed the presence of pigmented fungal elements. Excisional surgery was planned; in the meantime, a plaque-like lesion developed in the interorbital region. Histopathological examination confirmed the presumptive diagnosis of phaeohyphomycosis, and Exophiala spinifera was identified as the aetiological agent. Itraconazole, given orally at a dose of 10 mg/kg for 8 weeks following surgery, enabled clinical resolution despite continued use of immunosuppressants. The follow-up was carried out over 14 weeks. Relevance and novel information This case report provides the first evidence of multifocal cutaneous phaeohyphomycosis caused by E spinifera with clinical resolution after combined surgical and itraconazole treatment in an immunocompromised cat.

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“…The inhibition ratio of CYP3A by ESV is approximately 0.93 [ 6 , 15 , 16 ], which is a strong CYP3A-inhibitory effect similar to that of itraconazole [ 16 ]. The concentration/dose ratio of TAC increases 2.7-fold when co-administered with itraconazole [ 17 ]. In our case 1, TAC levels increased approximately threefold, suggesting that the degree of interaction between ESV and TAC was comparable to that between itraconazole and TAC.…”

Section: Discussionmentioning

confidence: 99%

Influence of ensitrelvir or nirmatrelvir/ritonavir on tacrolimus clearance in kidney transplant recipients: a single-center case series

Naganawa,

Katada,

Nakagawa

et al. 2024

J Pharm Health Care Sci

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Background Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug–drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered. However, the influence of ESV on blood TAC levels has not yet been reported, and the management of TAC doses during the use of ESV remains unclear. Case presentation We experienced three kidney transplant recipients with COVID-19, whose blood trough levels of TAC increased by the concomitant use of NMV/RTV or ESV. In two patients administering NMV/RTV, blood trough levels of TAC increased more than tenfold after combination therapy, whereas in one patient administering ESV, TAC level increased approximately threefold. Conclusions These cases suggest that TAC administration should be discontinued during NMV/RTV treatment to maintain blood TAC levels within the therapeutic range, and a reduced TAC dose is sufficient during ESV treatment.

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Effect of Itraconazole and Its Metabolite Hydroxyitraconazole on the Blood Concentrations of Cyclosporine and Tacrolimus in Lung Transplant Recipients

Cited by 5 publications

References 24 publications

Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia

Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia

Multifocal cutaneous phaeohyphomycosis caused by Exophiala spinifera with clinical resolution in an immunocompromised cat

Influence of ensitrelvir or nirmatrelvir/ritonavir on tacrolimus clearance in kidney transplant recipients: a single-center case series

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