TABLE 3

Antifungal agents for the treatment of pulmonary aspergillosis

Antifungal classDrugsDosageTherapeutic useComments
PolyenesDeoxycholate amphotericin B1–1.5 mg·kg−1 once daily (intravenous only)Should be avoided (privilege lipid formulations of amphotericin B if available)Monitor kidney function and electrolytes (K+)

Consider co-administration of paracetamol if fever and/or rigors

Consider alternative therapy for Aspergillus terreus
Liposomal amphotericin B3–5 mg·kg−1 once daily (intravenous only)Treatment of IPA (second choice after triazoles; first choice in areas with high prevalence of azole-resistant Aspergillus fumigatus isolates if no culture/fungigram available)
Amphotericin B lipid complex5 mg·kg−1 once daily (intravenous only)Treatment of IPA (privilege liposomal amphotericin B if available)
Amphotericin B colloidal dispersion6 mg·kg−1 once daily (intravenous only)Treatment of IPA (privilege liposomal amphotericin B if available)
TriazolesItraconazole200 mg once daily or twice daily (intravenous or oral)
TDM recommended (target: Ctrough: 1–4 mg·L−1)
Treatment of CPAMonitor hepatic tests (ALT, AST, ALP, GGT, bilirubin)

Monitor ECG (QT interval, in particular voriconazole)

DDIs (in particular voriconazole)

Consider alternative therapy for Aspergillus calidoustus or cryptic species of section Fumigati (e.g. Aspergillus lentulus)
VoriconazoleIntravenous: 6 mg·kg−1 twice daily (D1), then 4 mg·kg−1 twice daily
Oral: 400 mg twice daily (D1), then 200–300 mg twice daily
TDM recommended (target: Ctrough: 1–5 mg·L−1)
Treatment of IPA (first choice)
Treatment of CPA
PosaconazoleIntravenous or oral tablets: 300 mg twice daily (D1), then 300 mg once daily
Oral suspension: 200 mg three times daily
TDM recommended (target: Ctrough: >1 mg·L−1 for therapy and >0.7 mg·L−1 for prophylaxis)
Prophylaxis or treatment of IPA
Treatment of CPA (privilege itraconazole or voriconazole)
Oral suspension should be avoided or limited to prophylaxis (privilege intravenous formulation or oral tablets)
Isavuconazole200 mg three times daily (D1–2), then 200 mg once daily
TDM not routinely recommended (may be considered)
Treatment of IPA
Treatment of CPA (privilege itraconazole or voriconazole)
EchinocandinsCaspofungin70 mg (D1), then 50 mg once daily (intravenous only)Treatment of IPA as monotherapy (third choice after triazoles and lipid formulations of amphotericin B)
Treatment of IPA in combination with triazoles (severe cases and/or positive GM; azole-resistant Aspergillus fumigatus isolates)
Anidulafungin200 mg (D1), then 100 mg once daily (intravenous only)
Micafungin100 mg once daily (intravenous only)

ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CPA: chronic pulmonary aspergillosis; D1: day 1; DDI: drug–drug interaction; GGT: gamma glutamyltranspeptidase; GM: galactomannan; IPA: invasive pulmonary aspergillosis; TDM: therapeutic drug monitoring, W1: week 1.