LIPOSOMAL AMPHOTERICIN-B - THERAPEUTIC USE IN THE MANAGEMENT OF FUNGAL-INFECTIONS AND VISCERAL LEISHMANIASIS

Incorporation of amphotericin B into small unilamellar liposomes (AmBi some(R)) alter the pharmacokinetic properties of the drug, but allows it to retain significant in vitro and in vivo activity against fungal species. including Candida, Aspergillus and Cryptococcus, and parasite s of the genus Leishmania. Used as prophylaxis against fungal infectio ns in immunocompromised patients, liposomal amphotericin B appeared to reduce the incidence of both fungal colonisation and proven fungal in fections, but did not affect overall survival. Empirical therapy with liposomal amphotericin B in immunocompromised adults or children with suspected fungal infections was at least as effective as therapy with conventional amphotericin B. In the largest noncomparative studies, li posomal amphotericin B produced mycological eradication in 40 and 83% of patients with proven Candida infections and 41 and 60% with proven Aspergillus infections; however, these studies included relatively few patients. Mycological eradication rates of 67 to 85% in patients with cryptococcal meningitis have bern reported Liposomal amphotericin B i s an effective treatment for visceral leishmaniasis in immunocompetent adults and children, including those with severe or drug resistent di sease. The drug also produces good response rates in immunocompromised patients; however, relapse rates in these patients are high. Liposoma l amphotericin B is generally well tolerated. Few patients require dis continuation or dose reduction of the drug because of adverse events. The most frequently reported adverse events are hypokalaemia, nephroto xicity and infusion-related reactions; however, these occur significan tly less often after liposomal amphotericin B than after the conventio nal formulation of the drug. The acquisition cost of liposomal amphote ricin B is higher than that of conventional amphotericin B. Cost-effec tiveness analyses did not clearly show an economic benefit for empiric al liposomal amphotericin B antifungal therapy in adults; however; one model suggested that initial empirical therapy with the liposomal for mulation in children may cost less per cure that initial therapy with the conventional formulation. Liposomal amphotericin B appears to be a n effective alternative to conventional amphotericin B in the manageme nt of immunocompromised patients with proven or suspected fungal infec tions. Use of the drug is facilitated by its greatly improved tolerabi lity profile compared with conventional amphotericin B. Because of thi s, liposomal amphotericin should be preferred to conventional amphoter icin B in the management of suspected or proven fungal infections in i mmunocompromised patients with pre-existing renal dysfunction, amphote ricin B-induced toxicity or failure to respond to conventional amphote ricin B. Liposomal amphotericin B may also be considered for first- or second-line treatment of immunocompetent patients with visceral leish maniasis.