Treatment of Aspergillosisa | ||||
| INDICATION | PRIMARY TREATMENT | PRECAUTIONS | SECONDARY TREATMENT | COMMENTS |
|---|---|---|---|---|
| Invasive diseaseb | Voriconazole, isavuconazole | Drug interactions (especially with rifampin and carbamazepine)c | AmB, caspofungin, posaconazole, micafungin | As primary therapy, voriconazole and isavuconazole have a 20% higher response rate than AmB. Therapeutic drug monitoring is recommended for voriconazole. |
| Prophylaxis | Posaconazole tablet, itraconazole solution | Diarrhea and vomiting with itraconazole, vincristine interaction | Micafungin, aerosolized AmB | Some centers monitor plasma levels of itraconazole and posaconazole. |
| Single aspergilloma | Surgery | Multicavity disease: poor outcome of surgery, medical therapy preferable | Itraconazole, voriconazole, intracavity AmB | Single large cavities with an aspergilloma are best resected. |
| Chronic pulmonary diseaseb | Itraconazole, voriconazole | Poor absorption of itraconazole capsules with proton pump inhibitors or H2 blockers | Posaconazole, IV AmB, IV micafungin | Resistance may emerge during treatment, especially if plasma drug levels are subtherapeutic. |
| ABPA/SAFS (“fungal asthma”) | Itraconazole | Some glucocorticoid interactions, including with inhaled formulations | Voriconazole, posaconazole | Long-term therapy is helpful in most cases. No evidence indicates whether therapy modifies progression to bronchiectasis/fibrosis. |
a For information on duration of therapy, see text.
b An infectious disease consultation is appropriate for these pts.
c Online drug-interaction resource: www.aspergillus.org.uk/content/antifungal-drug-interactions.
Note: After loading doses, the oral dose is usually 200 mg bid for voriconazole and itraconazole, 300 mg qd for posaconazole tablets, and 200 mg qd for isavuconazole. The IV dose of voriconazole for adults is 6 mg/kg twice at 12-h intervals (loading doses) followed by 4 mg/kg q12h; a larger dose is required for children and teenagers; a lower dose may be safer for persons >70 years of age. Plasma monitoring is helpful in optimizing the dosage. The IV dose of isavuconazole is 200 mg tid for 2 days (loading dose) followed by 200 mg qd. Caspofungin is given as a single loading dose of 70 mg and then at 50 mg/d; some authorities use 70 mg/d for pts weighing >80 kg, and lower doses are required with hepatic dysfunction. Micafungin is given as 50 mg/d for prophylaxis and as at least 150 mg/d for treatment; this drug has not yet been approved by the U.S. Food and Drug Administration (FDA) for this indication. AmB deoxycholate is given at a daily dose of 1 mg/kg if tolerated. Several strategies are available for minimizing renal dysfunction. Lipid-associated AmB is given at 3 mg/kg (AmBisome) or 5 mg/kg (Abelcet). Different regimens are available for aerosolized AmB, but none is FDA approved. Other considerations that may alter dose selection or route include age; concomitant medications; renal, hepatic, or intestinal dysfunction; and drug tolerability.
Abbreviations: AmB, amphotericin B; ABPA, allergic bronchopulmonary aspergillosis; SAFS, severe asthma with fungal sensitization.