Therapeutic Drug Monitoring for Isavuconazole in Invasive Pulmonary Mucormycosis
TDM is not currently appropriate for this patient receiving isavuconazole for invasive pulmonary mucormycosis. Unlike other triazole antifungals, routine therapeutic drug monitoring is not recommended for isavuconazole based on current guidelines.
Rationale for Not Recommending TDM for Isavuconazole
Current Guideline Recommendations
The Infectious Diseases Society of America (IDSA) guidelines specifically state that while TDM is strongly recommended for triazoles like voriconazole, itraconazole, and posaconazole, "further studies are needed to address whether TDM is helpful or necessary... for isavuconazole" 1.
Similarly, the ESCMID-ECMM-ERS guideline indicates that limited data are currently available to define a target therapeutic range or support the need for routine TDM for isavuconazole 1. The guideline gives isavuconazole TDM only a CIII recommendation (low-quality evidence, expert opinion only), and only in specific clinical scenarios:
- Patients unresponsive to treatment
- Patients with unexpected toxicity
- Patients with pharmacokinetic drug-drug interactions
- When treating pathogens with elevated MICs
- When treating sanctuary sites such as the CNS
Pharmacokinetic Considerations
Isavuconazole demonstrates:
- More predictable pharmacokinetics than other triazoles
- Better oral bioavailability
- Less inter-patient variability
- Fewer drug-drug interactions compared to other triazoles
Special Considerations for This Patient
Renal Impairment
The patient has experienced significant acute kidney injury from liposomal amphotericin B. This is precisely why isavuconazole was chosen, as it:
- Does not require dose adjustment in renal impairment
- Has demonstrated efficacy against mucormycosis similar to amphotericin B 2
- Is well-tolerated in patients with renal dysfunction 3
Administration via Enteral Feeding Tube
While the patient is receiving isavuconazole via enteral feeding tube, this administration route does not specifically warrant TDM according to current guidelines. The dosing regimen prescribed (200 mg every 8 hours for 6 doses, then 200 mg daily) follows standard recommendations.
When TDM Would Be Appropriate
If any of the following situations develop during the patient's treatment course, TDM could be considered:
- Clinical deterioration despite appropriate therapy
- Suspected drug-drug interactions affecting isavuconazole levels
- Unexpected toxicity
- Treatment of CNS involvement or other sanctuary sites
In such cases, a trough level in the range of 2-3 mg/L (measured after day 5 of therapy, including loading doses) would suggest adequate drug exposure 1.
Contrast with Other Triazoles
For context, TDM is strongly recommended for:
- Voriconazole: Target trough of 1-5.5 mg/L, measured after 2-5 days of therapy 1
- Itraconazole: Target trough of 1-4 mg/L (by HPLC) for treatment, measured on day 5 1
- Posaconazole: Target trough varies by formulation and indication
Conclusion
Based on current guidelines and the specific clinical scenario, TDM is not currently appropriate for this patient receiving isavuconazole for invasive pulmonary mucormycosis. The focus should remain on clinical monitoring for treatment response and potential adverse effects.