Important Instructions for Intravenous Administration

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Intravenous formulation must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron).

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Infuse the intravenous formulation over a minimum of 1 hour in 250 mL of a compatible diluent, to reduce the risk for infusion-related reactions. Do not administer as an intravenous bolus injection.

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Do not infuse CRESEMBA with other intravenous medications.

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Flush intravenous lines with 0.9% sodium chloride injection, USP or 5% dextrose injection, USP prior to and after infusion of CRESEMBA.

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After dilution of the intravenous formulation, avoid unnecessary vibration or vigorous shaking of the solution. Do not use a pneumatic transport system.

​2.2 Dosage Regimen

​CRESEMBA (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. Prescribe CRESEMBA as shown in Table 1​ below.

​Switching between the intravenous and oral formulations of CRESEMBA is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.

​With oral administration, swallow capsules whole. Do not chew, crush, dissolve, or open the capsules. CRESEMBA capsules can be taken with or without food.

Reconstitution Instructions for the Injection Formulation

Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in CRESEMBA or in the materials specified for reconstitution. CRESEMBA is water soluble, preservative-free, sterile, and nonpyrogenic.

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Reconstitute one vial of CRESEMBA by adding 5 mL water for injection, USP to the vial.

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Gently shake to dissolve the powder completely.

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Visually inspect the reconstituted solution for particulate matter and discoloration. Reconstituted CRESEMBA should be clear and free of visible particulate.

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The reconstituted solution may be stored below 25°C for a maximum of 1 hour prior to preparation of the patient intravenous infusion solution [see Dosage and Administration (2.4)].

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For nasogastric tube administration, the reconstituted solution should be administered within 1 hour of reconstitution [see Dosage and Administration (2.5)].

Dilution and Preparation Instructions for the Intravenous Administration of the Injection Formulation

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Remove 5 mL of the reconstituted solution from the vial and add it to an infusion bag containing 250 mL (approximately 1.5 mg isavuconazonium sulfate per mL) of compatible diluent. The diluted solution may show visible translucent to white particulates of isavuconazole (which will be removed by in-line filtration).

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Use gentle mixing or roll bag to minimize the formation of particulates. Avoid unnecessary vibration or vigorous shaking of the solution.

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Apply in-line filter with a microporous membrane pore size of 0.2 to 1.2 micron and in-line filter reminder sticker to the infusion bag.

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Do not use a pneumatic transport system.

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The intravenous administration should be completed within 6 hours of dilution at room temperature. If this is not possible, immediately refrigerate (2°C to 8°C / 36°F to 46°F) the infusion solution after dilution and complete the infusion within 24 hours. Do not freeze the infusion solution.

Preparation Instructions for the Nasogastric Tube Administration of the Injection Formulation

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Utilizing aseptic technique, reconstitute one vial of CRESEMBA for injection (equivalent to 200 mg isavuconazole) with 5 mL of water for injection, USP [see Dosage and Administration (2.3)].

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Withdraw the entire contents (5 mL) of the vial using an appropriate syringe and needle. Discard the needle and cap the syringe.

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To administer, remove the cap from the syringe containing the reconstituted solution and connect the syringe to the nasogastric (NG) tube to deliver the dose. After administering the dose, administer three 5 mL rinses to the NG tube with water [see Clinical Pharmacology (12.3)].

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The reconstituted solution should be administered via nasogastric tube within 1 hour of reconstitution.

Compatibility for the Injection Formulation

CRESEMBA for injection should only be administered with the following diluents:

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0.9% sodium chloride injection, USP

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5% dextrose injection, USP