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Table 3 Primary antifungal treatment options for the treatment of IA and special considerations in solid organ transplant recipients

From: Invasive aspergillosis in solid organ transplant patients: diagnosis, prophylaxis, treatment, and assessment of response

Agent Dose Recommendation Potential Adverse Events Potential Drug Interactions Additional Considerations Monitoring
Voriconazole Induction: 6 mg/kg IVa every 12 h the first day
Maintenance: 4 mg/kg IVa, 200-300 mg PO twice daily
1st line [14] -Hepatotoxicityb
-Visual changes
-Neurologic toxicity
-Rash and photosensitivity
-Periostitis
-QTc prolongationc
-Sirolimusd
-Tacrolimusd
-Cyclosporined
-Non-linear pharmacokinetics
-Strong inhibitor of CYP3A4
-Moderate inhibitor of CYP2C19 and 2C9
-Metabolized via CYP2C19, 2C9 and 3A4
- < 2% of voriconazole is excreted in the urine
-Liver function tests
−12-lead ECGf
-Voriconazole TDMd
-Sirolimus, tacrolimus, and cyclosporine TDMd
Isavuconazole Induction: 200 mg three times daily the first 2 days
Maintenance: 200 mg daily
1st line [15]
Primary alternative [14]
-Hepatotoxicityb -Sirolimuse
-Tacrolimuse
-Cyclosporinee
-Linear pharmacokinetics
-Moderate inhibitor of CYP3A4
-Metabolized via CYP3A4
-Isavuconazole may cause QTc shortening
-Liver function tests
-Sirolimus, tacrolimus, and cyclosporine TDMe
Liposomal Amphotericin B 3–5 mg/kg daily IV Primary alternative [14, 15] - Nephrotoxicityg    -Renal function and electrolytes
  1. IV Intravenous, PO Oral, ECG Electrocardiogram, TDM Therapeutic Drug Monitoring
  2. aIV voriconazole is not recommended in patients with renal dysfunction (glomerular filtration rate < 50 mL/min) due to the potential of nephrotoxicity associated with the IV formulation vehicle of cyclodextrin
  3. bHepatotoxicity was significantly less frequent in patients treated with isavuconazole as compared to voriconazole in a prospective randomized clinical trial [89]
  4. cIsavuconazole is associated with shortening of the QTc interval
  5. dVoriconazole may significantly increase sirolimus levels, therefore close monitoring of sirolimus TDM is recommended in case of co-administration. Significant dose reductions of sirolimus, tacrolimus and cyclosporine are commonly required when any of these agents is co-administered with voriconazole
  6. eEarly data suggest that isavuconazole administration does not significantly affect blood concentrations of sirolimus and tacrolimus [90]. Until more data become available, it is advised to closely monitor immunosuppression TDM while co-administered with isavuconazole
  7. fIn cases of baseline QTc prolongation and/or co-administration with QTc prolonging agents, such as macrolides and fluroquinolones, regular QTc monitoring is recommended
  8. gAdditional, noteworthy toxicities include hypomagnesaemia, renal tubular acidosis, and elevated liver function tests