How do you switch from amphotericin B to isavuconazole for maintenance therapy?

Switching from Amphotericin B to Isavuconazole for Maintenance Therapy

When switching from amphotericin B to isavuconazole for maintenance therapy, wait until the patient has shown a favorable clinical response to amphotericin B, then transition to isavuconazole 200 mg orally twice daily for the remainder of the treatment course.

General Principles for Switching from Amphotericin B to Oral Azoles

• Amphotericin B is typically used as initial therapy until the patient has shown a favorable response and can take an oral antifungal agent; then, an oral azole is given for the remainder of the treatment course 1
• The transition from amphotericin B to oral therapy should occur after clinical improvement is observed, which typically happens within 1-2 weeks of amphotericin B therapy 1
• For severe fungal infections, amphotericin B (either deoxycholate or lipid formulation) is recommended for initial treatment, followed by step-down to oral azole therapy after clinical improvement 1

Specific Protocol for Switching to Isavuconazole

• After the patient shows clinical improvement on amphotericin B (typically 3-10 days of therapy), transition to isavuconazole maintenance therapy 1
• Isavuconazole should be initiated with a loading dose regimen:
  • 200 mg (equivalent to 372 mg isavuconazonium sulfate) three times daily for the first 2 days (6 doses total)
  • Then continue with 200 mg once daily as maintenance dose 2, 3
• No overlap period between amphotericin B and isavuconazole is typically required 3

Monitoring During Transition

• Monitor the patient closely during the first week after transition for signs of clinical deterioration that might indicate treatment failure 1
• Check liver function tests before starting isavuconazole and at regular intervals (at 1,2, and 4 weeks and then every 3 months) during therapy 1
• Unlike with itraconazole, routine therapeutic drug monitoring is not typically required for isavuconazole 2

Duration of Maintenance Therapy

• For most invasive fungal infections, maintenance therapy with isavuconazole should continue for at least 12 months total treatment duration 1
• For immunocompromised patients, especially those with HIV/AIDS, lifelong suppressive therapy may be required if immunosuppression cannot be reversed 1

Special Considerations

• Isavuconazole has better oral bioavailability than itraconazole and does not require food or acidic conditions for absorption 3
• Unlike itraconazole, isavuconazole does not require therapeutic drug monitoring, making it easier to manage in the outpatient setting 2
• Isavuconazole has been successfully used as salvage therapy in patients who failed or were intolerant to amphotericin B 2, 4

Potential Pitfalls and Caveats

• Ensure that the patient has truly responded to initial amphotericin B therapy before switching to oral therapy, as premature discontinuation of amphotericin B may lead to treatment failure 1
• Consider potential drug interactions with isavuconazole before initiating therapy 3
• For pregnant patients, azoles (including isavuconazole) should be avoided due to potential teratogenicity; amphotericin B remains the preferred agent throughout pregnancy 1