FLUCONAZOLE - AN UPDATE OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND THERAPEUTIC USE IN MAJOR SUPERFICIAL AND SYSTEMIC MYCOSESIN IMMUNOCOMPROMISED PATIENTS

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in pati ents with AIDS or as treatment or primary prophylaxis in neutropenia a ssociated with cancer therapy. Fluconazole also resolves symptoms in u p to 60% of patients with cryptococcal meningitis and AIDS. However, i n their infection its efficacy as treatment relative to that of amphot ericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction, In this regar d, fluconazole has been proven superior to amphotericin B and to itrac onazole 200 mg/day. Comparisons with other drugs used for the treatmen t of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effectiv e as clotrimazole and ketoconazole; it was more so than the fatter azo le in 1 study. In patients undergoing chemotherapy or bone marrow tran splantation fluconazole as primary prophylaxis has produced greater cl inical benefit than a clotrimazole regimen. The incidence of adverse e vents appears to be somewhat higher in patients with AIDS compared wit h HIV-negative cohorts, but the qualitative pattern of events is simil ar The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconzole in ch ildren AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; wh ether the drug influences mortality, as has been suggested by one plac ebo-controlled trial in patients undergoing bone marrow transplant; an d the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of s econdary resistance resistance. Notwithstanding these undefined aspect s of its clinical profile, fluconazole is now confirmed as an importan t antifungal drug in the management of fungal infections in patients w ith immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and i s a preferred agent for secondary prophylaxis against candidal infecti ons; it is also a favored agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marr ow transplantation.