Achievement of clinical isavuconazole blood concentrations in transplant recipients with isavuconazonium sulphate capsules administered via enteral feeding tube. 2020

Erin K McCreary, and M Hong Nguyen, and Matthew R Davis, and Jared Borlagdan, and Ryan K Shields, and Anthony D Anderson, and Ryan M Rivosecchi, and Rachel V Marini, and Lauren M Sacha, and Fernanda P Silveira, and David R Andes, and Alexander J Lepak
Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA.

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.

UI MeSH Term Description Entries
D009570 Nitriles Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE. Nitrile
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002214 Capsules Hard or soft soluble containers used for the oral administration of medicine. Capsule,Microcapsule,Microcapsules
D004750 Enteral Nutrition Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. Enteral Feeding,Force Feeding,Nutrition, Enteral,Tube Feeding,Gastric Feeding Tubes,Feeding Tube, Gastric,Feeding Tubes, Gastric,Feeding, Enteral,Feeding, Force,Feeding, Tube,Feedings, Force,Force Feedings,Gastric Feeding Tube,Tube, Gastric Feeding,Tubes, Gastric Feeding
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000935 Antifungal Agents Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues. Anti-Fungal Agents,Antifungal Agent,Fungicides, Therapeutic,Antibiotics, Antifungal,Therapeutic Fungicides,Agent, Antifungal,Anti Fungal Agents,Antifungal Antibiotics
D014230 Triazoles Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3. Triazole
D066027 Transplant Recipients Individuals receiving tissues or organs transferred from another individual of the same or different species, or from within the same individual. Recipient, Transplant,Recipients, Transplant,Transplant Recipient

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