Anidulafungin

Echinocandin antifungal agent. Semi-synthetic echinocandin (lipopeptide) from a fermentation product of Aspergillus nidulans. Anidulafungin, like all antifungals from the group of echinocandins, acts as an inhibitor of glycan synthase. The preparation is approved for the treatment of candidemia in non-neutropenic adult patients. In clinical studies, the preparation showed superiority over fluconazole in invasive candidiasis (Reboli AC et al. 2007).

Selective, non-competitive inhibition of the enzyme 1,3-ß-D-glucan synthase occurring in the fungal cell. This results in the inhibition of synthesis of 1,3-ß-D-glucan, an essential component of the fungal cell wall. The cell walls become defective and brittle and the fungus can no longer continue to grow. The enzyme 1,3-β-D-glucan synthase is found only in fungi and not in humans. The lack of glycan fibrils leads to disturbances in the cell wall structure of the fungus.

• In vivo fungicidal activity against Candida spp. including fluconazole-resistant species, especially C. albicans, C. tropicalis, C. glabrata, C. krusei.
• In vivo limited activity against C. parapsilosis, C. guilliermondii and C. lusitaniae.
• In vitro good activity against Aspergillus spp, esp, against A. fumigatus, Aspergillus flavus, A. terreus. Good activity against trophic and cystic forms of Pneumocystis jiroveci.
• Limited efficacy in vitro against Bipolaris spp, Cladiophialophora bantiana, Pseudallescheria boydii, Scedosprium prolificans, Histoplasma capsulatum.
• Not effective against: T. beigelii, Blastomyces dermatitidis, Sporothrix schenckii, Rhizopus spp., Fusarium spp.

It is not known whether anidulafungin passes into breast milk. Available pharmacodynamic/toxicological data in animals show a transfer of anidulafungin into breast milk.

Common: diarrhoea, nausea, vomiting, flushing, blood coagulation disorders, convulsions, headache, pruritus, exanthema, thrombocytopenia, hypokalaemia, hyperkalaemia, hypomagnesaemia and disorders of other blood parameters.Unlike amphotericin B, anidulafungin has a lower risk of nephrotoxicity.

Liver: Elevated liver enzyme levels have been observed in both healthy subjects and patients treated with anidulafungin. Some patients with severe underlying diseases who received anidulafungin together with various other concomitant medications experienced clinically relevant disturbances in liver function.

Anaphylactic reactions: Anaphylactic reactions, including shock, have been reported with the use of anidulafungin. If such reactions occur, anidulafungin should be discontinued and appropriate therapy initiated.

Infusion-Related Reactions: Inf usion-related reactions, including rash, urticaria, flushing, pruritus, dyspnea, bronchospasm, and hypotension, have been reported with the use of anidulafungin. As long as the infusion rate of anidulafungin does not exceed 1.1 mg/min, infusion-related reactions rarely occur.

Anidulafungin is not a clinically relevant substrate, inducer or inhibitor of cytochrome P450 isozymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A).

Hypersensitivity to the drug and other drugs from the class of echinocandins (eg, caspofungin).

Hereditary fructose intolerance (the preparation contains fructose).

Neonates: The safety and efficacy of anidulafungin in neonates (aged < 1 month) has not been established and is not recommended. Treatment of neonates requires consideration of coverage for disseminated candidiasis, including central nervous system (CNS); nonclinical infection models indicate that higher doses of anidulafungin are required for adequate CNS penetration, resulting in higher doses of the other ingredient polysorbate 80,. An association of high doses of polysorbates with potentially life-threatening toxicities in neonates has been reported in the literature.

Patients with hereditary fructose intolerance.

Anidulafungin STADA® 100 mg powder for a concentrate for the preparation of an infusion solution; Ecalta® 100 mg powder.

• Remember! Anidulafungin is very poorly soluble in water. The finished infusion solution contains 24 Vol% ethanol. This corresponds to 6 g ethanol in the maintenance dose of 100 mg or 12 g ethanol in the initial dose of 200 mg.

• Caution! The alcohol content can influence the effectiveness of other drugs and impair the ability to drive or operate machines.