Antibiotic, Antifungal, Antiviral Drugs

Systematic drug interaction studies have not been performed to date using amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal. The fact that drug interactions reported with conventional IV amphotericin B could also occur with these lipid-based or liposomal formulations of the drug should be considered.

Acute infusion reactions (e.g., fever, chills, headache, nausea, vomiting) and nephrotoxicity are the most frequent adverse reactions to conventional IV amphotericin B. Although clinical experience with amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, and amphotericin B liposomal is limited to date, these drugs appear to be better tolerated than conventional IV amphotericin B.

Conventional amphotericin B is administered by IV infusion. The drug also has been given intra-articularly, intrapleurally, intrathecally, or by local instillation or irrigation. For information regarding administration of the drug as an oral suspension and administration of the drug topically, subconjunctivally, or by local instillation or irrigation.

Conventional IV amphotericin B (formulated with sodium desoxycholate) is used for the treatment of potentially life-threatening fungal infections including aspergillosis, North American blastomycosis, systemic candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, paracoccidioidomycosis,, sporotrichosis, and zygomycosis.

Caspofungin acetate, a semisynthetic lipopeptide synthesized from a fermentation product of Glarea lozoyensis, is an echinocandin antifungal agent. The drug is a glucan synthesis inhibitor and differs structurally and pharmacologically from other currently available antifungal agents. Caspofungin inhibits the synthesis of b(1,3)-d-glucan, an integral component of the fungal cell wall that is not present in mammalian cells.

Efficacy has been demonstrated in clinical studies in patients for primary therapy of invasive aspergillosis, for primary and salvage therapy of invasive aspergillosis, and for treatment of invasive aspergillosis in patients whose disease was refractory to, or who were intolerant of, other antifungal therapy. Aspergillus fumigatus was the most frequent isolate in patients with aspergillosis participating in clinical trials with the drug. A complete or partial response was achieved in 48% of patients in this study, with lower response rates observed in patients with definite disease (38%) than in those with probable disease (58%).

Voriconazole, a triazole antifungal agent, is a synthetic derivative of fluconazole. Like other azole antifungal agents, voriconazole presumably exerts its antifungal activity by altering cellular membranes, resulting in increased permeability, secondary metabolic effects, and growth inhibition. Although the exact mechanism of action of voriconazole has not been fully determined, the drug inhibits cytochrome P-450-dependent sterol 14-a-demethylase in susceptible fungi, which leads to accumulation of C-14-methylated sterols (e.g., lanosterol) and decreased concentrations of ergosterol. Voriconazole is active in vitro against Aspergillus fumigatus, A. flavus, A. niger, and A. terreus.

Ketoconazole is administered orally. To ensure absorption in patients with achlorhydria, it has been recommended that each 200 mg of ketoconazole be dissolved in 4 mL of 0.2N hydrochloric acid solution or taken with 200 mL of 0.1N hydrochloric acid.

Oral ketoconazole is used in the treatment of blastomycosis, candidal infections (i.e., oropharyngeal and/or esophageal candidiasis, vulvovaginal candidiasis, candiduria, chronic mucocutaneous candidiasis),chromomycosis (chromoblastomycosis), coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis.

Itraconazole generally is well tolerated. However, serious potentially life-threatening adverse effects, including congestive heart failure, pulmonary edema, and hepatotoxicity, have occurred rarely in patients receiving IV or oral itraconazole. In clinical studies evaluating itraconazole for the treatment of systemic fungal infections, adverse effects requiring discontinuance of the drug occurred in up to 11% of patients; the median duration of therapy before discontinuance was 81 days (range: 2-776 days).