Aspergillosis Medication

Updated: Jan 10, 2019
  • Author: Eloise M Harman, MD; Chief Editor: Guy W Soo Hoo, MD, MPH  more...
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Medication

Medication Summary

The treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) requires intravenous antifungal therapy. Voriconazole is usually first-line therapy, sometimes in combination with other agents, such as caspofungin. Another triazole antifungal agent, isavuconazole, is also indicated for invasive aspergillosis. Amphotericin may sometimes be prescribed in treatment failures.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction treated with corticosteroids. The addition of oral antifungal therapy with itraconazole may be beneficial in the management of ABPA. Aspergillomas may respond to prolonged oral itraconazole therapy. Intracavitary therapy with amphotericin has also been used in small numbers of patients.

Further inpatient and outpatient medications

ABPA therapy includes oral prednisone and, in selected cases, oral itraconazole, usually for several months. As the patient is tapered off oral steroids, inhaled corticosteroids should be added for control of underlying asthma. The concomitant use of inhaled budesonide and oral itraconazole has been found to cause adrenal suppression in a significant proportion of patients with cystic fibrosis (CF) and ABPA.

For aspergilloma, oral itraconazole therapy may be beneficial. A Japanese study found that 60% of patients with aspergilloma had some response to oral itraconazole. In patients with bilateral aspergillomas or severe underlying disease preventing surgical resection, oral itraconazole therapy may be continued for several months.

For invasive aspergillosis and CNPA, specific antifungal therapy with oral or intravenous voriconazole is the usual initial therapy. Response to therapy may be poor. In patients who respond, prolonged therapy may be required.

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Antifungal agents

Class Summary

Their mechanism of action may involve increasing the permeability of the cell membrane, which, in turn, causes intracellular components to leak.

Amphotericin B (Abelcet, AmBisome)

Amphotericin B is a polyene antibiotic produced by a strain of Streptomyces nodosus. It can be fungistatic or fungicidal. It binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. Newer lipid formulations are as effective as the original formulation and have less nephrotoxicity. Use may be associated with fever, rigors, and nausea (premedication with hydrocortisone and meperidine may be beneficial). Adequate hydration may decrease nephrotoxicity, and patients who can tolerate fluid should be administered prehydration and posthydration.

Itraconazole (Sporanox, Onmel, Tolsura)

Itraconazole is a synthetic triazole antifungal agent with greater activity against Aspergillus than fluconazole or ketoconazole. It has fungistatic activity. Itraconazole slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

It is available in oral formulations (eg, capsule, suspension) and is useful for prolonged antifungal therapy. A new oral formulation of itraconazole is also available that uses SUBA (SUper-BioAvailable) technology to improve the bioavailability of poorly soluble drugs.

Caspofungin (Cancidas)

Caspofungin is an antifungal with efficacy against A fumigatus,A flavus, and Aspergillus terreus. It is the first of a new class of antifungals called echinocandins. It works on a component of fungal cell walls that is not present in mammalian cells. Caspofungin is indicated for Aspergillus infection in patients who are refractory to or cannot tolerate other therapies. It has not been studied for primary therapy.

Voriconazole (VFEND)

Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. It is a triazole antifungal agent that inhibits fungal cytochrome P-450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Posaconazole (Noxafil)

Posaconazole is a triazole antifungal agent. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

It is available as an oral suspension (200 mg/5 mL), 100-mg delayed-release tablet, and injection. Posaconazole injection is administered as a loading dose of 300 mg twice on the first day of treatment, followed by 300 mg once daily thereafter. The tablets are administered as a loading dose of 300 mg twice daily on day 1, followed by a once-daily maintenance dose of 300 mg.

Isavuconazonium sulfate (Cresemba)

Isavuconazole is a triazole antifungal agent. Isavuconazole is the active moiety of the prodrug isavuconazonium sulfate. It is indicated for invasive aspergillosis and has activity against most strains of the following microorganisms, both in vitro and in clinical infection: Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger.

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Corticosteroids

Class Summary

Corticosteroids are useful in the management of allergic reactions. These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

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