Some of the views expressed in the following notes on newly approved products should be regarded as tentative, as there may have been limited published data and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. As a result of fuller experience, initial comments may need to be modified. The Committee is prepared to do this. Before new drugs are prescribed, the Committee believes it is important that full information is obtained either from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Noxafil (Schering-Plough)
105 mL glass bottles containing 40 mg/mL suspension
Approved indication: specified fungal infections
Australian Medicines Handbook section 5.2.1
The increase in patients with disorders of the immune system or taking immunosuppressants has led to an increase in fungal infections. The drugs available to treat systemic fungal infections include amphotericin B and the triazole antifungals such as itraconazole and voriconazole.
Like other triazole antifungals, posaconazole inhibits the synthesis of ergosterol. This results in the breakdown of the fungal cell membrane. In vitro, posaconazole is active against species of aspergillus and fusarium. It is also approved for use in chromoblastomycosis, coccidiodomycosis, mycetoma and zygomycosis.
Patients take the suspension twice a day. Doses are taken with meals as food more than doubles the absorption of posaconazole. The half-life is 35 hours so it takes at least a week for concentrations to reach a steady state. Most of the drug is excreted unchanged in the faeces. There is some metabolism, but cytochrome P450 is not extensively involved. Posaconazole does inhibit P450 3A4 so it may reduce the metabolism of drugs such as calcium channel blockers, midazolam, atorvastatin and simvastatin. Drugs which reduce plasma concentrations of posaconazole include phenytoin, rifabutin, H2receptor antagonists and, probably, proton pump inhibitors.
Posaconazole has mainly been studied in infections that were resistant to other drugs. Its approval is therefore limited to patients who cannot tolerate other antifungals or have a refractory infection. In a study of fungal infections of the central nervous system, patients were treated with posaconazole for up to a year. Most patients had already been treated with amphotericin. Treatment with posaconazole was successful in 14 of the 29 patients with cryptococcal meningitis and five of the 10 patients with other infections.1
During the trials of posaconazole the most frequently reported problems were fever, gastrointestinal upsets and headache. Other adverse effects included neutropenia, anorexia, dizziness, fatigue and rash. Posaconazole can alter liver function and may also potentially prolong the QTc interval in the ECG.
Refractory fungal infections are difficult to treat so there is a need for new antifungal drugs, but already organisms with reduced susceptibility to posaconazole have been identified. There is limited published information about the clinical effectiveness of posaconazole so it is not possible to evaluate if it has any advantage over other antifungals such as voriconazole.
Reference †
1. Pitisuttithum P, Negroni R, Graybill JR, Bustamante B, Pappas P, Chapman S, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother 2005;56:745-55.
The T-score ( 
) is explained in 'Two-way
transparency', Aust Prescr 2005;28:103.
