Mucormycosis (Zygomycosis) Medication

Updated: Jul 06, 2021
  • Author: Avnish Sandhu, DO; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Medication

Medication Summary

The 2 main classes of antifungal medications used to treat mucormycosis are the polyenes (amphotericin formulations) and triazoles (isavuconazole and posaconazole). Amphotericin B and isavuconazole are the 2 agents currently FDA approved for the primary therapy of mucormycosis. Posaconazole can be used off-label for salvage treatment in patients intolerant to amphotericin B. It has also been used as step-down therapy after initial control of the disease with amphotericin. [95, 96]

In patients with hematologic malignancy, posaconazole is superior to other triazoles as prophylaxis for invasive mold infection. Isavuconazole is a novel triazole antifungal agent with many advantages, including excellent oral bioavailability, linear and predictable pharmacokinetics, and minimal CYP450 interactions. [89] Owing to its safety, tolerability, and comparable efficacy to amphotericin B, [86] isavuconazole is promising as a primary and salvage therapy. Further study is needed prior to its use as primary mold prophylaxis in the setting of prolonged neutropenia.

Echinocandin agents, including anidulafungin, caspofungin, and micafungin, competitively inhibit the beta-1,3-D-glucan synthase enzyme complex. In Candida species, beta-glucan depletion causes cell lysis via loss of resistance to osmotic force; in Aspergillus, it is fungistatic owing to impaired growth at hyphal branching points. Echinocandins have minimal activity against the Mucorales, which contain little or no beta-1,3-D-glucan. Some studies have suggested combination therapy with amphotericin and an echinocandin may improve survival; however, a more recent retrospective study showed no such mortality benefit. There is no current evidence-based recommendation for the addition of an echinocandin to amphotericin B or isavuconazole for the treatment of mucormycosis.

The benefit of combination therapy with different classes of antifungals (including echinocandins) is uncertain. Despite advances in medical management, surgical evaluation is essential in the management of mucormycosis, and overall mortality rates remain high.

See the Treatment section for further discussion of individual antifungal agents.

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Antifungal agents, Polyene

Class Summary

These agents bind irreversibly to ergosterol within the fungal cell membrane. This binding results in disruption of membrane integrity, leakage of intracellular components, and, ultimately, cell death.

Liposomal amphotericin B (AmBisome)

Consists of a mixture of phosphatidylcholine, cholesterol, and distearoyl phosphatidylglycerol that arrange into amphotericin B–containing unilamellar vesicles in aqueous media. First-line therapy for mucormycosis at 5 mg/kg/d. Owing to decreased risk of nephrotoxicity at this dose, it can be used in the setting of preexisting renal dysfunction and when nephrotoxicity develops during amphotericin B deoxycholate therapy. Careful electrolyte monitoring and replacement is required.

Amphotericin B lipid complex (Abelcet)

Amphotericin B lipid complex is amphotericin B in phospholipid complexed form. This is an alternate therapy to liposomal amphotericin B.

Amphotericin B deoxycholate

Less commonly used than the lipid formulations because of higher rates of nephrotoxicity but less costly and more widely available. The typical dose is 1-1.5 mg/kg/d. The total dose given over the course of therapy is usually 2.5-3 g.

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Antifungal agents, Azole derivatives

Class Summary

These agents inhibit the cytochrome P450-dependent 14-alpha-lanosterol demethylase of the fungal cell membrane. Toxic cell membrane sterols accumulate and ergosterol production is inhibited, leading to impaired growth and replication and, ultimately, cell death.

Isavuconazonium sulfate (Cresemba)

Novel triazole approved in 2015 for the treatment of mucormycosis. It has equivalent oral and IV bioavailability and a favorable safety/tolerability profile. The oral prodrug isavuconazonium sulfate is rapidly converted to the active isavuconazole moiety. Initial dosing is isavuconazonium sulfate 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses, followed by maintenance with 372 mg once daily.

Posaconazole (Noxafil)

Used off-label for salvage therapy in patients intolerant to amphotericin B or as step-down therapy after initial polyene treatment. Administered as one 300-mg tablet twice on day 1 followed by 300 mg orally once daily with or without food. The delayed-release tablet formulation is preferred over the oral suspension because of its more reliable absorption. An intravenous formulation is also available.

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