McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 1 1  Antifungal agents

Pharmacokinetics Anidulafungin is given as a daily IV infusion for at least 14 days. It has a rapid onset of action, is metabolised by degradation and has a half-life of 40 to 50 hours. This drug is excreted in the faeces. Caspofungin is available for IV use. This drug is slowly metabolised in the liver, with half-lives of 9 to 11 hours, then 6 to 48 hours and then 40 to 50 hours. It is bound to protein and widely distributed throughout the body. It is excreted through the urine. Contraindications and cautions Anidulafungin may cross the placenta and enter breast milk and should not be used by pregnant or breastfeed- ing women. Caution must be used in the presence of hepatic impairment because it can be toxic to the liver. Caspofungin can be toxic to the liver; therefore, reduced doses must be used if a person has known hepatic impairment. Caspofungin is embryotoxic in animal studies and is known to enter breast milk; therefore, it should be used with great caution during pregnancy and breastfeeding. Adverse effects Anidulafungin and caspofungin are associated with hepatic toxicity, and liver function should be monitored closely when using these drugs. Clinically important drug–drug interactions Concurrent use of cyclosporin with caspofungin is contraindicated unless the benefit clearly outweighs the risk of hepatic injury. O ther antifungal agents Other antifungal drugs that are available do not fit into either of these classes. These include amphotericin B ( Abelcet , AmBisome , Fungilin ), flucytosine ( Ancotil ), griseofulvin ( Grisovin ) and nystatin ( Kenacomb, Mycostatin , Nilstat ). Therapeutic actions and indications Other antifungal agents work to cause fungal cell death or to prevent fungal cell reproduction. Amphotericin B is a very potent drug with many unpleasant adverse effects (see Adverse effects). The drug binds to the sterols in the fungus cell wall, changing cell wall permeability. This change can lead to cell death (fungicidal effect) or prevent the fungal cells from reproducing (fungistatic effect). (See Table 11.1 for usual indications.) Because of the many adverse effects associated with this agent, its use is reserved for progressive, potentially fatal infections.

Flucytosine is a less toxic drug that alters the cell membrane of susceptible fungi, causing cell death (see Table 11.1 for usual indications). Griseofulvin is an older antifungal that acts in much the same way, changing cell membrane permeability and causing cell death. Nystatin binds to sterols in the cell wall, changing membrane permeability and allowing leaking of the cellular components, which will result in cell death. Pharmacokinetics Amphotericin B and flucytosine are available in IV form. They are excreted in the urine, with an initial half-life of 24 hours and then a 15-day half-life. Their metabolism is not fully understood. Flucytosine is well absorbed from the GI tract, with peak levels occurring in 2 hours. Most of the drug is excreted unchanged in the urine and a small amount in the faeces, with a half-life of 2.4 to 4.8 hours. Griseofulvin is administered orally and reaches peak levels in around 4 hours. It is metabolised in the liver and excreted in the urine with a half-life of 24 hours. Nystatin is not absorbed from the GI tract and passes unchanged in the stool. Contraindications and cautions Amphotericin B has been used successfully during pregnancy, but it should be used cautiously. It crosses into breast milk and should not be used during breast- feeding because of the potential risk to the neonate. Because flucytosine is excreted primarily in the urine, extreme caution is needed in the presence of renal impairment because drug accumulation and toxicity can occur. Toxicity is associated with serum levels higher than 100 mcg/mL. Because of the potential for adverse reactions in the fetus or neonate, flucytosine should be used during pregnancy and breastfeeding only if the benefits clearly outweigh the risks. It is not known whether nystatin crosses the placenta or enters breast milk, so it should not be used during pregnancy or breastfeeding unless the benefits clearly outweigh the potential risks. Adverse effects Adverse effects of these drugs are related to their toxic effects on the liver and kidneys. People should be moni- tored closely for any changes in liver or kidney functions. Bone marrow suppression has also been reported with the use of these drugs as well as rash and dermatological changes. Amphotericin B is associated with severe renal impairment, bone marrow suppression, GI irritation with nausea, vomiting and potentially severe diarrhoea, anorexia and weight loss, and pain at the injection site with the possibility of phlebitis or thrombophlebitis. Adverse effects of griseofulvin are relatively mild, with