About Isavuconazole Dosing

This information supports the use of the Isavuconazole Dose Calculator by explaining the key parameters and dosing principles. Isavuconazole (CRESEMBA®) is an azole antifungal agent used to treat invasive aspergillosis and invasive mucormycosis. Dosing involves a loading phase to quickly achieve therapeutic concentrations, followed by a maintenance phase for continued treatment.

Outputs Explained

The calculator provides a recommended dosing regimen based on patient parameters. Key outputs include:

• Loading Dose: The initial higher dose administered for the first 48 hours. Presented as mg of isavuconazonium sulfate and its equivalent in mg of isavuconazole base.
• Maintenance Dose: The ongoing daily dose after the loading phase is complete. Also shown in both sulfate and base forms.
• Administration Instructions: Specific guidance based on the selected formulation (IV or Oral).
• Clinical Notes: Important considerations regarding organ function (hepatic/renal) and major drug interactions.

How to Use This Information

To understand the dosing principles, consider the following inputs from the calculator:

1. Patient Type: Select "Adult" for individuals aged 18 years and older or "Pediatric" for those under 18.
2. Pediatric Parameters: If "Pediatric" is chosen, enter the patient's age (years and months) and weight (kg or lbs). These are crucial for weight-based dosing calculations.
3. Formulation: Choose between "Intravenous (IV)" for infusion or "Oral" for capsules.
4. Hepatic & Renal Function: Select the patient's liver and kidney function status to receive relevant safety alerts, although dose adjustments are generally not required based on renal function.

Dosing Overview

Adult Dosing (≥18 Years)

Dosing for adults is standardized and not based on weight.

• Loading Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg isavuconazole) every 8 hours for 6 doses.
• Maintenance Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg isavuconazole) once daily, starting 12 to 24 hours after the last loading dose.

Pediatric Dosing (1 to <18 Years)

Dosing for pediatric patients is typically weight-based at 10 mg/kg, but it should not exceed the standard adult dose. The regimen follows the same loading and maintenance schedule.

• Loading Dose: 10 mg/kg/dose (up to a maximum of 372 mg) every 8 hours for 6 doses.
• Maintenance Dose: 10 mg/kg/dose (up to a maximum of 372 mg) once daily.

Switching Between IV and Oral

Isavuconazole has high oral bioavailability. Patients can be switched between the intravenous and oral formulations on a 1:1 basis when clinically appropriate. For example, a patient receiving 372 mg IV can be switched to 372 mg (two 186 mg capsules) orally.

Missed Dose Protocol

If a patient misses a maintenance dose, they should take it as soon as they remember on the same day. If they do not remember until the next day, they should skip the missed dose and take the next dose at the regularly scheduled time. The patient should not take two doses to make up for a missed one.

Safety Alerts

• Hepatic Impairment: Use in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended unless the potential benefit outweighs the risk, as clinical data is limited.
• Renal Impairment: No dose adjustment is needed for patients with any degree of renal impairment, including those with end-stage renal disease (ESRD) on hemodialysis.
• Drug Interactions: Isavuconazole is a substrate and moderate inhibitor of CYP3A4. Co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole) or strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John’s Wort) is contraindicated.

Frequently Asked Questions (FAQ)

Why are two different milligram amounts shown (e.g., 372 mg and 200 mg)?

Isavuconazole is administered as a prodrug, isavuconazonium sulfate. 372 mg of the sulfate prodrug is equivalent to 200 mg of the active isavuconazole base. Both are commonly referenced in clinical practice and literature.

Is the adult dose based on weight?

No, the adult dose is a fixed amount and is not adjusted for the patient's body weight.

Do I need to adjust the dose for a patient on dialysis?

No, the prescribing information states that no dose adjustment is required for any level of renal impairment, including patients on hemodialysis.

Can the oral capsules be opened or crushed?

No, the capsules must be swallowed whole. They should not be chewed, crushed, dissolved, or opened, as this can affect the drug's absorption.

How is the intravenous (IV) form administered?

After reconstitution and dilution, the IV solution should be administered over a minimum of one hour through an in-line filter with a pore size of 0.2 to 1.2 microns.

Is the dose different for invasive aspergillosis vs. invasive mucormycosis?

No, the recommended dosing regimen is the same for both FDA-approved indications.

What age range is considered "pediatric" for dosing purposes?

The pediatric dosing regimen applies to patients aged 1 year to less than 18 years. Safety and effectiveness have not been established in patients younger than 1 year.

Why might a 16-year-old receive the full adult dose?

Pediatric dosing is calculated at 10 mg/kg but is capped at the adult dose of 372 mg. If a pediatric patient's weight results in a calculated dose exceeding 372 mg (i.e., they weigh over 37.2 kg), they will receive the standard adult dose.

References

1. CRESEMBA® (isavuconazonium sulfate) Prescribing Information. U.S. Food and Drug Administration.
2. Cresemba (isavuconazole) Summary of Product Characteristics. European Medicines Agency.
3. Dosing and Administration for CRESEMBA. Pfizer for Professionals.
4. Treatment for Aspergillosis. U.S. Centers for Disease Control and Prevention (CDC).