Anidulafungin (Eraxis or Ecalta, Pfizer) was the first of the echinocandins to be discovered, and the third to be licensed for clinical use. It is a semi-synthetic modification of a fermentation product from the fungus Aspergillus nidulans. The lead compound for anidulafungin (LY303366) was identified in 1974. Numerous modifications failed to generate an orally bioavailable analogue and so Lilly out-licensed the product to Versicor (then Vicuron) in June 1999. Clinical studies commenced in 1998, but it was not licensed until 2006. It inhibits the function of beta-(1,3)-D-glucan synthase.
Dose & Delivery
Anidulafungin is used to treat candidaemia and invasive candidiaisis. It is intravenous only. The standard dose is a 200mg loading dose with each subsequent dose being 100mg, each given once a day. No dosage adjustments are required for those with renal or hepatic insufficiency. Very few data support treatment in children.
Fungi the drug is active against
Anidulafungin is active against all species of Candida. It is extremely active and usually rapidly fungicidal against all species except Candida parapsilosis, Candida guilliermondii and Candida famata against which it is moderately active. It has potent activity against Candida biofilms, which azoles in general do not. Resistant C. glabrata isolates are recognized, some of which may retain susceptibility to other echinocandins. Resistance in C. albicans, C. tropicalis and C. krusei isolates have also been described usually confirmed by mutations in 2 hot spots in the target gene.
Anidulafungin is also active against all Aspergillus species, but not fungicidal. It is not antagonistic when given in combination with amphotericin B or azoles against Aspergilli. Resistance in A. fumigatus is described with anidulafungin and all the echinocandins, but difficult to measure with confidence. Anidulafungin has limited activity against Coccidioides spp., Blastomyces dermatitidis, Scedosporium spp., Paecilomyces varioti and Histoplasma spp. which is not sufficient for clinical use.
For candidaemia, 200mg loading dose then 100mg a day.
Metabolism and excretion
The drug is chemically degraded slowly in the body and has a large volume of distribution (30-50L). Like other echinocandins, anidulafungin is extensively bound (>99%) to human plasma proteins.
Anidulafungin is not an inhibitor and is a poor substrate for cytochrome people P450 enzymes, so no drug interactions are documented. View drug interactions database
The commonest side effects (all less than 1 in 40 patients) were flushing or a hot flush, pruritus, rash and/or urticaria. Raised liver enzymes occur in about 1 in 40 patients. Other side effects appear to be rare.
Long term side effects have not been established with the echinocandins because they are relatively new compounds. For anidulafungin, a maximum duration of therapy of 35 days is recommend, based on current preclinical exposure data.
Structure of anidulafungin