When is therapeutic drug monitoring (TDM) appropriate for a patient switched to isavuconazole (Isavuconazonium sulfate) due to acute kidney injury on liposomal amphotericin B (Amphotericin B) for invasive mucormycosis treatment?

Therapeutic Drug Monitoring for Isavuconazole in Invasive Mucormycosis

TDM is not currently appropriate for this patient receiving isavuconazole for invasive pulmonary mucormycosis.

Rationale for Not Recommending TDM for Isavuconazole

Isavuconazole demonstrates more predictable pharmacokinetics than other triazole antifungals, with less inter-patient variability and fewer drug-drug interactions. According to the ESCMID-ECMM-ERS guidelines, there is limited data to support routine therapeutic drug monitoring (TDM) for isavuconazole, giving it only a CIII recommendation (low-quality evidence) 1.

The guidelines specifically state that TDM for isavuconazole should be considered only in specific clinical scenarios:

• Treatment failure
• Unexpected toxicity
• Significant drug-drug interactions
• Treatment of pathogens with elevated MICs
• Infections in sanctuary sites such as the CNS 1, 2

Clinical Management Approach

Current Treatment Assessment

• The patient has been appropriately switched from liposomal amphotericin B to isavuconazole due to acute kidney injury
• The dosing regimen (200 mg every 8 hours for 6 doses, then 200 mg once daily) follows recommended guidelines for mucormycosis 1
• The administration via enteral feeding tube is appropriate as isavuconazole capsules can be opened and administered this way

Monitoring Strategy

1. Focus on clinical response rather than drug levels

   • Monitor for resolution of symptoms and radiographic improvement
   • Assess for adverse effects of isavuconazole

2. Monitor renal function

   • Track recovery from amphotericin B-induced acute kidney injury
   • Isavuconazole has less nephrotoxicity compared to amphotericin B 3, 4

3. Consider TDM only if:

   • Clinical deterioration occurs despite appropriate therapy
   • Unexpected drug toxicity develops
   • Significant drug-drug interactions are introduced
   • The infection spreads to the CNS 1, 2

Comparison with Other Triazoles

Unlike other triazole antifungals, isavuconazole does not have a strong recommendation for routine TDM:

• Voriconazole: Requires TDM with target trough of 1-5.5 mg/L
• Posaconazole: Requires TDM with target trough >1 mg/L for treatment
• Itraconazole: Requires TDM with target trough of 1-4 mg/L 1, 2

Treatment Duration Considerations

Treatment with isavuconazole should continue until:

• Complete response on imaging (though scarring may persist)
• Resolution of immunosuppression
• Clinical improvement 1

The typical duration is often prolonged (weeks to months) based on clinical response, with a median of 84 days reported in clinical studies 3.

Common Pitfalls to Avoid

1. Don't routinely perform TDM for isavuconazole without a specific indication as mentioned above
2. Don't discontinue therapy prematurely - mucormycosis requires prolonged treatment
3. Don't miss monitoring for potential drug interactions - although fewer than other triazoles, they can still occur
4. Don't forget surgical evaluation - surgical debridement remains an important component of mucormycosis management when feasible 1

In conclusion, while TDM is valuable for many antifungal agents, current evidence does not support routine TDM for isavuconazole in this patient with invasive pulmonary mucormycosis. Clinical monitoring for treatment response and potential adverse effects should be the focus of management.