- Aust Prescr 2009;32:165-71
- 1 December 2009
- DOI: 10.18773/austprescr.2009.081
vials containing 100 mg powder for reconstitution
Approved indication: invasive candidiasis
Australian Medicines Handbook section 5.2.2
Invasive fungal infections are relatively common in hospitalised patients, particularly those who are immunosuppressed or taking antibiotics. Many of these infections are caused by Candida species, especially Candida albicans and Candida glabrata. Conditions such as candidal oesophagitis are often managed with an azole antifungal. If the fungi are resistant, an echinocandin antifungal such as caspofungin may be used.
Anidulafungin is another echinocandin. These drugs act by inhibiting a fungal enzyme, glucan synthase, which is essential for the integrity of the fungal cell wall. Anidulafungin has activity against Aspergillus as well as against Candida.
As anidulafungin is not well absorbed orally, it has to be diluted and given as a daily intravenous infusion, starting with a loading dose. The drug is not metabolised, but slowly degrades. Very little is excreted in the urine so dose reductions are not needed for patients with renal or hepatic impairment.
A phase II trial randomised 123 patients with invasive candidiasis to receive an infusion of 50 mg, 75 mg or 100 mg for up to 42 days. Although 33 patients died during the study, the results suggested that higher doses of anidulafungin produced a better response.1 At a dose of 100 mg daily, it eradicated Candida from 89% of the evaluable patients.2 This dose was then evaluated in a phase III trial.
In the trial, 131 patients were given intravenous anidulafungin and 125 were given intravenous fluconazole. Most of the patients had candidaemia and many had previously taken fluconazole. Patients who responded to at least 10 days of intravenous therapy could then start oral fluconazole. After a median of 14-15 days treatment there was a favourable response in 76% of the anidulafungin group and 60% of the fluconazole group. The mortality was 23% with anidulafungin and 31% with fluconazole.3
Anidulafungin has been studied for other indications. A double-blind trial has compared intravenous anidulafungin with oral fluconazole in 601 patients with oesophageal candidiasis. After a median duration of therapy of 14 days the symptoms resolved in almost all patients, with a response confirmed by endoscopy in 87% of the anidulafungin group and 88% of the fluconazole group.4
Adverse reactions to the infusion such as flushing and rash may be minimised by infusing the drug slowly. The frequency of adverse events is similar to that seen with intravenous fluconazole.3 Like fluconazole, anidulafungin has been associated with altered hepatic function. In the phase II trial the most frequent adverse events were hypotension, vomiting, nausea and fever.1
Although anidulafungin has efficacy in candidiasis there is insufficient evidence to show that it is superior to fluconazole. While the drugs appeared similar in the treatment of oesophageal candidiasis, more patients in the anidulafungin group had relapsed when followed up two weeks after treatment.4 As few of the patients in the trials had neutropenia, the efficacy of anidulafungin for treating invasive candidiasis in this group is unknown. While an azole antifungal may remain a first choice, drug interactions or the microbiological results may prompt consideration of an echinocandin. However, there are insufficient data to determine if anidulafungin has any advantages over caspofungin.
The Transparency Score () is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.