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ONCOLOGY. Vol. 15 No. 11 9
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A Brief Review of Antifungal Therapy for Deep Fungal Infection

By

Raymond J. Muller, RPH, MS
Associate Director, Division of Pharmacy Services, Memorial Sloan-Kettering Cancer Center, New York, New York

| November 1, 2001
With the continuing increase in clinically important fungal disease, especially seen in the neutropenic patient, the need for new and improved systemic antifungal agents marches on. A pharmacy and therapeutics committee may select an antifungal agent based on these criteria: spectrum of action, pharmacokinetic profile, toxicity, potential for resistance, and cost. A number of agents are now available for treating deep fungal infections, including amphotericin B in conventional and liposomal formulations, and the triazoles itraconazole (Sporanox) and fluconazole (Diflucan). It is important to note that there is lack of agreement in practice over what constitutes ideal therapy. The lipid formulations of amphotericin B and the improved oral solution and new intravenous formulation of itraconazole are recent additions to therapeutic options that are already having a significant influence on drug selection and treatment practices. [ONCOLOGY 15(Suppl 9):21-25, 2001]

Several antifungal agents are now available for use against fungal disease, including amphotericin B(Drug information on amphotericin b), itraconazole(Drug information on itraconazole) (Sporanox), and fluconazole(Drug information on fluconazole) (Diflucan). It is important to note that there is a lack of agreement in practice over what constitutes ideal therapy. The following overview explains the current options along with the guidelines used at Memorial-Sloan Kettering Cancer Center (MSKCC) in New York.

General recommendations of drugs of choice for the various fungal indications are shown in Table 1.[1] Potential adverse reactions, contra- indications, and drug interactions associated with these agents are shown in Table 2.

Amphotericin B

Conventional Formulation

Amphotericin B is a potent broadspectrum agent that has been in clinical use for 40 years.[2-6] Until the availability of itraconazole, it was the only agent available for treating Aspergillus infection. A major drawback of conventional amphotericin B is its toxicity profile, with renal toxicity (including acute tubular necrosis) constituting the primary adverse effect associated with treatment. Hypokalemia is a recurrent problem that warrants strict attention to use of other drugs that can affect potassium balance (eg, cisplatin [Platinol], ifosfamide [Ifex], corticosteroids, and ticarcillin(Drug information on ticarcillin)/clavulanic acid [Timentin]).

Other characteristic toxicities include nausea, vomiting, and anorexia; increased erythropoietin(Drug information on erythropoietin) production; phlebitis, if the drug is administered through a peripheral intravenous (IV) line; and (rarely) thrombocytopenia or leukopenia. Acute reactions consist of the complex of chills, fever, tachypnea, hypoxemia, and hypotension; premedication protocols including acetaminophen, hydrocortisone(Drug information on hydrocortisone), diphenylamine, or meperidine are helpful in alleviating these reactions.

Lipid Formulations

The lipid formulations of amphotericin B that have become available are associated with a degree of reduction in renal toxicity compared with the conventional formulation.[4,5,7] However, it is far from clear whether this reduced toxicity and improved quality of life is worth a cost that can be up to 50 times that of the standard formulation for the drug alone.

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