Isavuconazonium

Renal Impairment Of the 403 patients who received CRESEMBA in the Phase 3 trials, 79 (20%) of patients had an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m 2 . No dose adjustment is needed in patients with mild, moderate, or severe renal impairment, including those patients with End-Stage Renal Disease (ESRD) [see Clinical Pharmacology] .

Hepatic Impairment No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology] . CRESEMBA has not been studied in patients with severe hepatic impairment (Child‑Pugh Class C) and should be used in these patients only when the benefits outweigh the risks.

Clinical monitoring for CRESEMBA-related adverse reactions is recommended when treating patients with severe hepatic impairment [see Warnings and Precautions] .

Important Administration Instructions for CRESEMBA CRESEMBA for Injection

CRESEMBA for injection is intended for use in patients who are 1 year of age and older [see Dosage and Administration ( 2.2 and 2.3 )].

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

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.

Do not infuse CRESEMBA with other intravenous medications.

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

After dilution of the intravenous formulation, avoid unnecessary vibration or vigorous shaking of the solution. Do not use a pneumatic transport system. Nasogastric Tube Administration of CRESEMBA for Injection

CRESEMBA for injection via nasogastric (NG) tube administration is intended for use by patients who are 6 years of age and older and weighing 16 kg and greater [see Dosage and Administration ( 2.2 , 2.3 and 2.6 ] . CRESEMBA Capsules

CRESEMBA capsules are intended for use in patients who are 6 years of age and older and weighing 16 kg and greater [see Dosage and Administration ( 2.2 and 2.3 )].

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 CRESEMBA capsules whole. Do not chew, crush, dissolve, or open the capsules. CRESEMBA capsules can be taken with or without food.

Recommended Dosage and Administration in Adult Patients Recommended dosage and administration of CRESEMBA for injection and capsules in adult patients is described in Table 1 below. CRESEMBA (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. [See table below.] CRESEMBA Capsules, 74.5 mg 74.5 mg 74.5 mg of isavuconazonium sulfate is equivalent to 40 mg of isavuconazole. of isavuconazonium sulfate per capsule Five 74.5 mg capsules (372 mg ) orally every 8 hours for 6 doses (48 hours) Five 74.5 mg capsules (372 mg ) orally once daily

Recommended Dosage and Administration in Pediatric Patients Recommended dosage and administration of CRESEMBA for injection and CRESEMBA capsules in pediatric patients is described in Table 2 below [see Clinical Pharmacology ] . The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA. [See table below.]

Reconstitution Instructions for the CRESEMBA for 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.

Reconstitute one vial of CRESEMBA by adding 5 mL water for injection, USP to the vial. The resultant solution will be 74.4 mg/mL of isavuconazonium sulfate.

Gently shake to dissolve the powder completely.

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

The reconstituted solution may be stored between 5°C to 25°C (41°F to 77°F) for a maximum of 1 hour prior to preparation of the patient intravenous infusion solution [see Dosage and Administration].

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

Discard any unused portion of the reconstituted solution.

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

Based on the adult or pediatric dosage regimen [see Dosage and Administration ( 2.2 and 2.3 )], remove the appropriate volume of the reconstituted solution (74.4 mg/mL of isavuconazonium sulfate) from the vial and add it to an infusion bag containing 250 mL of compatible diluent [see Dosage and Administration] . A smaller volume infusion bag of compatible diluent may be used as long as the final concentration does not exceed approximately 1.5 mg isavuconazonium sulfate per mL.

The diluted solution may show visible translucent to white particulates of isavuconazole (which will be removed by in-line filtration).

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

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.

Do not use a pneumatic transport system.

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.