Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Takesue, Yoshio; Hanai, Yuki; Oda, Kazutaka; Hamada, Yukihiro; Mayumi, Toshihiko; Matsumoto, Kazuaki; Fujii, Satoshi; Takahashi, Yoshiko; Miyazaki, Yoshitsugu; Kimura, Toshimi

doi:10.1016/j.clinthera.2022.10.005

Cited by 28 publications

(24 citation statements)

References 144 publications

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“…Voriconazole is an antifungal drug used in the treatment or prophylaxis of invasive aspergillosis and candidiasis [ 25 ]. Serum concentrations of voriconazole can have considerable interpatient variability, with demonstrated higher hepatotoxicity rate in Asian vs. non-Asian populations [ 26 ]. A systematic review and meta-analysis selected the optimal trough concentration of voriconazole for adult patients with invasive fungal infections between 1.0 and 4.0 μg/mL [ 27 ].…”

Section: Systemic Mycosis and Pharmacological Therapymentioning

confidence: 99%

Antifungal Drug Resistance: An Emergent Health Threat

Vitiello

Ferrara²,

Boccellino

et al. 2023

Biomedicines

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Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

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Section: Systemic Mycosis and Pharmacological Therapymentioning

confidence: 99%

Antifungal Drug Resistance: An Emergent Health Threat

Vitiello

Ferrara²,

Boccellino

et al. 2023

Biomedicines

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“…Although it presents lower urinary concentration, it is ideal that during the use of voriconazole, its serum concentration should be dosed. It is a drug metabolized by cytochrome P450, and the maintenance of adequate therapeutic serum levels is essential to avoid adverse effects such as hepatic and neurological toxicity [ 11 , 12 ]. The serum level presented by the patient was 3.3 mg/L, within the therapeutic range.…”

Section: Discussionmentioning

confidence: 99%

Urinary Aspergillosis in a Patient with Systemic Lupus Erythematosus (SLE)

Toledo

Alves

Cambruzzi³

et al. 2023

Case Reports in Infectious Diseases

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Aspergillosis is an opportunistic mycosis that generally affects the lungs. The fungus was cleared by the immune system of a healthy host. Extrapulmonary forms are very rare, and there are few reports of urinary aspergillosis. In this case report, we describe a 62-year-old woman with systemic lupus erythematosus (SLE) with complaints of fever and dysuria. The patient had recurrent episodes of urinary tract infection and several hospitalizations. A computed tomography revealed an amorphous mass in the left kidney and bladder. After partial resection of the material was referred for analysis, Aspergillus infection was suspected and confirmed by culture. Successful treatment with voriconazole was provided. Diagnosis of localized primary renal Aspergillus infection in a patient with SLE requires careful investigation due to its benign presentation and lack of associated systemic clinical features.

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“…Voriconazole concentrations were measured in‐house at one hospital and by an external laboratory at another hospital using high‐performance liquid chromatography with a lower limit of quantification of 0.1 μg/mL. The therapeutic C min range was set at 1.0–4.0 μg/mL in this study 17,23 . Follow‐up TDMs were performed in patients to achieve the therapeutic range with dose adjustment based on the result of the initial TDM.…”

Section: Methodsmentioning

confidence: 99%

“…The therapeutic C min range was set at 1.0-4.0 μg/mL in this study. 17,23 Follow-up TDMs were performed in patients to achieve the therapeutic range with dose adjustment based on the result of the initial TDM.…”

Section: Protocol For Tdmmentioning

confidence: 99%

“…Meanwhile, with a q12h loading dose on the initial day, plasma levels increased rapidly and a similar C min was maintained from the third day to the tenth day of multiple dosing. The latest Japanese guidelines for TDM of voriconazole recommend that the initial TDM be performed on days 3–5 in patients receiving loading doses 17 . A higher rate of poor metabolisers of voriconazole due to genetic polymorphisms of CYP2C19 has been observed among Asians compared to non‐Asians, 18,19 and a prolonged half‐life might result in a delay in achieving the steady state of voriconazole in Asians.…”

Section: Introductionmentioning

confidence: 99%

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Optimal timing for therapeutic drug monitoring of voriconazole to prevent adverse effects in Japanese patients

Hanai

Hamada

Oda

et al. 2023

Mycoses

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BackgroundThe optimal timing for therapeutic drug monitoring (TDM) of voriconazole in Asians, who have higher rates of poor metabolisers than non‐Asians, is unclear. This can cause unexpectedly high concentrations and delays in reaching steady‐state levels.ObjectivesTo determine the appropriate timing of TDM in Japanese patients receiving voriconazole.Patients/MethodsTrough levels (Cmin) were measured on days 3–5 (recommended timing, RT) and days 6–14 (delayed timing, DT) after starting voriconazole in patients receiving an appropriate dosage. Considering bioavailability, Cmin was only compared in patients receiving oral voriconazole.ResultsA total of 289 and 186 patients were included in the safety and pharmacokinetic analyses, respectively. There was a significant difference in Cmin measured no later than and after day 5 (3.59 ± 2.12 [RT] vs. 4.77 ± 3.88 μg/mL [DT], p = .023), whereas no significant difference was observed on cutoff day 6 (3.91 ± 2.60 vs. 4.40 ± 3.94 μg/mL, p = .465), suggesting that Cmin close to the steady‐state was achieved after day 5. DT causes a delay in achieving the therapeutic range. The hepatotoxicity rates were 21.5% and 36.8% in the RT and DT groups, respectively (p = .004); DT was an independent risk factor for hepatotoxicity.ConclusionAlthough steady‐state concentrations may not be achieved by day 5, early dose optimisation using RT can prevent hepatotoxicity in Japanese patients. TDM should be performed on days 3–5 to ensure safety. However, subsequent TDM may be necessary due to a possible further increase in Cmin.

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Clinical Practice Guideline for the Therapeutic Drug Monitoring of Voriconazole in Non-Asian and Asian Adult Patients: Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

Cited by 28 publications

References 144 publications

Antifungal Drug Resistance: An Emergent Health Threat

Antifungal Drug Resistance: An Emergent Health Threat

Urinary Aspergillosis in a Patient with Systemic Lupus Erythematosus (SLE)

Optimal timing for therapeutic drug monitoring of voriconazole to prevent adverse effects in Japanese patients

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