Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Pharmacy, University of California Los Angeles Ronald Reagan Medical Center, Los Angeles, CA, USA.
J Antimicrob Chemother. 2020 Oct 1;75(10):3023-3028. doi: 10.1093/jac/dkaa274.
Isavuconazole is a triazole antifungal available in IV and capsule formulation. Prescribing information states that capsules should not be chewed, crushed, dissolved or opened because the drug was not studied in this manner. However, considering the pharmacokinetics of the capsules, we theorized opening and sprinkling the contents into an enteral feeding tube (EFT) would result in adequate absorption and systemic concentrations of isavuconazole.
To determine whether patients receiving isavuconazonium sulphate capsules via EFT would achieve clinical blood concentrations of isavuconazole.
Nineteen solid organ and HCT recipients receiving isavuconazole via EFT for prevention or treatment of invasive fungal infection (IFI) were prospectively identified at four academic medical centres in the USA. Patients were included in this evaluation if they received isavuconazole via EFT for at least 5 days and therapeutic drug monitoring (TDM) was performed.
TDM was performed after a median of 7 days (range 6-17) following EFT administration and 15 days (range 7-174) of isavuconazole therapy overall. Median isavuconazole concentration was 1.8 μg/mL (range 0.3-5.2). Median isavuconazole concentrations in patients with or without prior IV administration were 1.8 μg/mL (range 0.3-5.2) and 2.2 μg/mL (range 0.8-3.6; P = 0.896), respectively. Concentrations achieved with the EFT route were similar to or greater than the corresponding concentrations via the IV route in six patients who had TDM performed during both routes of administration.
It is reasonable to consider opening isavuconazonium sulphate capsules and administering the contents enterally for prevention and treatment of IFI.
伊曲康唑是一种三唑类抗真菌药物，有静脉注射和胶囊两种剂型。说明书指出，胶囊不能咀嚼、压碎、溶解或打开，因为药物尚未对此种用法进行研究。但是，鉴于胶囊的药代动力学特征，我们推测打开胶囊并将内容物撒入肠内营养管（EFT）中会导致伊曲康唑充分吸收并达到全身浓度。
确定通过 EFT 给予伊曲康唑硫酸盐胶囊的患者是否能达到伊曲康唑的临床血药浓度。
在美国的四个学术医疗中心，前瞻性地确定了 19 例接受伊曲康唑通过 EFT 预防或治疗侵袭性真菌感染（IFI）的实体器官和造血干细胞移植（HCT）受者。如果患者接受 EFT 给予伊曲康唑至少 5 天且进行了治疗药物监测（TDM），则将其纳入本评估中。
在 EFT 给药后中位数为 7 天（范围 6-17）进行 TDM，总体中位伊曲康唑治疗时间为 15 天（范围 7-174）。中位数伊曲康唑浓度为 1.8μg/mL（范围 0.3-5.2）。先前有或无 IV 给药的患者的中位数伊曲康唑浓度分别为 1.8μg/mL（范围 0.3-5.2）和 2.2μg/mL（范围 0.8-3.6；P=0.896）。在 6 名同时接受两种途径给药且进行 TDM 的患者中，EFT 途径达到的浓度与 IV 途径相当或更高。
对于预防和治疗 IFI，考虑打开伊曲康唑硫酸盐胶囊并将内容物经肠内给予是合理的。
