Isavuconazoniumdosage

Important Administration Instructions:

CRESEMBA for injection is intended for use in patients who are 1 year of age and older.

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..

CRESEMBA for injection must be administered through an in-line filter over a minimum of 1 hour..

CRESEMBA capsules are intended for use in patients who are 6 years of age and older and weighing 16 kg and greater.

CRESEMBA capsules can be taken with or without food.. Recommended Dosage in Adult Patients: Recommended Dosage for CRESEMBA in Adult Patients Dosage Form Loading Dose Maintenance Dose Start maintenance doses 12 to 24 hours after the last loading dose CRESEMBA for Injection, 372 mg/vial 372 mg of isavuconazonium sulfate per vial One reconstituted vial (372 mg) intravenously every 8 hours for 6 doses (48 hours) One reconstituted vial (372 mg) intravenously once daily CRESEMBA Capsules, 186 mg 186 mg of isavuconazonium sulfate per capsule Two 186 mg capsules (372 mg) orally every 8 hours for 6 doses (48 hours) Two 186 mg capsules (372 mg) orally once daily CRESEMBA Capsules, 74.5 mg 74.5 mg 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 in Pediatric Patients:

The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA. Recommended Dosage for CRESEMBA in Pediatric Patients Dosage Form Age Body Weight (kg) Loading Dose Maintenance Dose Start maintenance doses 12 to 24 hours after the last loading dose CRESEMBA for Injection, 372 mg/vial 372 mg of isavuconazonium sulfate per vial 1 to less than 3 years of age less than 18 kg 15 mg/kg intravenously every 8 hours for 6 doses (48 hours) 15 mg/kg intravenously once daily 3 to less than 18 years of age less than 37 kg 10 mg/kg intravenously every 8 hours for 6 doses (48 hours) 10 mg/kg intravenously once daily greater than or equal to 37 kg One reconstituted vial (372 mg) intravenously every 8 hours for 6 doses (48 hours) One reconstituted vial (372 mg) intravenously once daily CRESEMBA Capsules, 74.5 mg 74.5 mg of isavuconazonium sulfate per capsule 6 to less than 18 years of age 16 kg to less than 18 kg Two capsules (149 mg) orally every 8 hours for 6 doses (48 hours) Two capsules (149 mg) orally once daily 18 kg to less than 25 kg Three capsules (223.5 mg) orally every 8 hours for 6 doses (48 hours) Three capsules (223.5 mg) orally once daily 25 kg to less than 32kg Four capsules (298 mg) orally every 8 hours for 6 doses (48 hours) Four capsules (298 mg) orally once daily greater than or equal to 32 kg 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

2.1 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.

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. CRESEMBA Capsules

CRESEMBA capsules are intended for use in patients who are 6 years of age and older and weighing 16 kg and greater.

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.

2.2 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. Table 1. Recommended Dosage and Administration for CRESEMBA in Adult Patients Dosage Form Loading Dose Maintenance Dose Start maintenance doses 12 to 24 hours after the last loading dose. CRESEMBA for Injection, 372 mg/vial 372 mg 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole. of isavuconazonium sulfate per vial One reconstituted vial (372 mg ) intravenously every 8 hours for 6 doses (48 hours) One reconstituted vial (372 mg ) intravenously once daily CRESEMBA Capsules, 186 mg 186 mg 186 mg of isavuconazonium sulfate is equivalent to 100 mg of isavuconazole. of isavuconazonium sulfate per capsule Two 186 mg capsules (372 mg ) orally every 8 hours for 6 doses (48 hours) Two 186 mg capsules (372 mg ) orally once daily 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

2.3 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. The maximum of any individual loading or daily maintenance dose to be administered to any pediatric patient is 372 mg of CRESEMBA. Table 2. Recommended Dosage and Administration for CRESEMBA in Pediatric Patients Dosage Form Age Body Weight (kg) Loading Dose Maintenance Dose Start maintenance doses 12 to 24 hours after the last loading dose. CRESEMBA for Injection, 372 mg/vial 372 mg 372 mg of isavuconazonium sulfate is equivalent to 200 mg of isavuconazole. of isavuconazonium sulfate per vial 1 year to less than 3 years of age less than 18 kg 15 mg/kg intravenously every 8 hours for 6 doses (48 hours) 15 mg/kg intravenously once daily 3 years to less than 18 years of age less than 37 kg 10 mg/kg intravenously every 8 hours for 6 doses (48 hours) 10 mg/kg intravenously once daily greater than or equal to 37 kg One reconstituted vial (372 mg ) intravenously every 8 hours for 6 doses (48 hours) One reconstituted vial (372 mg ) intravenously once daily 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 6 to less than 18 years of age 16 kg to less than 18 kg Two capsules (149 mg) orally every 8 hours for 6 doses (48 hours) Two capsules (149 mg) orally once daily 18 kg to less than 25 kg Three capsules (223.5 mg) orally every 8 hours for 6 doses (48 hours) Three capsules (223.5 mg) orally once daily 25 kg to less than 32 kg Four capsules (298 mg) orally every 8 hours for 6 doses (48 hours) Four capsules (298 mg) orally once daily greater than or equal to 32 kg Five capsules Five 74.5 mg CRESEMBA capsules are equivalent to two 186 mg CRESEMBA capsules. (372 mg) orally every 8 hours for 6 doses (48 hours) Five capsules (372 mg) orally once daily

2.4 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.

For nasogastric tube administration, the reconstituted solution should be administered within 1 hour of reconstitution.

Discard any unused portion of the reconstituted solution.

2.5 Dilution and

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

Based on the adult or pediatric dosage regimen, 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. 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.

2.6 Preparation

Instructions for the Nasogastric Tube Administration of the CRESEMBA for Injection Formulation CRESEMBA for injection can be administered through a nasogastric tube as follows:

Utilizing aseptic technique, reconstitute one vial of CRESEMBA for injection (equivalent to 200 mg isavuconazole) with 5 mL of water for injection, USP.

Based on the adult or pediatric (6 years of age to less than 18 years of age) CRESEMBA for injection dosage regimen, withdraw the appropriate volume of the reconstituted solution (74.4 mg/mL of isavuconazonium sulfate) from the vial using an appropriate syringe and needle. Discard the needle and cap the syringe.

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.

Administer the reconstituted solution via the nasogastric tube within 1 hour of reconstitution. Discard any unused portion of the reconstituted solution.

Do not administer CRESEMBA capsules through a nasogastric tube.

2.7 Compatibility for the

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

0.9% sodium chloride injection, USP

5% dextrose injection, USP