McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

then switch to an oral form when the person’s condition improves and they are able to take oral medications. Ketoconazole is absorbed rapidly from the GI tract, with peak levels occurring within 1 to 3 hours. It is extensively metabolised in the liver and excreted through the faeces. Fluconazole reaches peak levels within 1 to 2 hours after administration. Most of the drug is excreted unchanged in the urine, so extreme caution should be used in the presence of renal dysfunction. Itraconazole is slowly absorbed from the GI tract and is metabolised in the liver by the CYP450 system. It is excreted in the urine and faeces. Posaconazole is given orally, has a rapid onset of action and peaks within 3 to 5 hours. It is metabolised in the liver and excreted in the faeces. Terbinafine is rapidly absorbed from the GI tract, extensively metabolised in the liver and excreted in the urine with a half-life of 36 hours. Voriconazole reaches peak levels in 1 to 2 hours if given orally, and at the onset of the infusion if given IV. It is metabolised in the liver with a half-life of 24 hours and is excreted in the urine. Contraindications and cautions Ketoconazole has been associated with severe hepatic toxicity and should be avoided in people with hepatic dysfunction. In addition, ketoconazole is not the drug of choice for people with endocrine or fertility problems. Although fluconazole should be used with caution in the presence of liver or renal impairment, fluconazole is not associated with the endocrine problems seen with ketoconazole. Itraconazole has been associated with hepatic failure, should not be used in people with hepatic failure and so should be used with caution in those with hepatic impairment. It is not known whether posaconazole 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. Caution should be used if posaconazole is used in the presence of liver impairment. Carefully monitor people for bone marrow suppression and GI and liver toxicity if using this drug. Terbinafine has been associated with severe liver toxicity and is contraindicated with liver failure. It may cross the placenta and may enter breast milk, so it should not be used in pregnant or breastfeeding women because of the potential toxic effects on the fetus or baby.

Voriconazole should not be used with any other drugs that prolong the QTc interval and can cause ergotism if taken with ergot alkaloids. Adverse effects Many of the azoles are associated with liver toxicity and can cause severe effects on a fetus or breastfeeding infant. Clinically important drug–drug interactions Ketoconazole and fluconazole strongly inhibit the CYP450 enzyme system in the liver and are associated with many drug–drug interactions, such as increased serum levels of the following agents: cyclosporin, digoxin, oral hypoglycaemics, warfarin, oral antico- agulants and phenytoin . If these combinations cannot be avoided, closely monitor individuals and anticipate the need for dose adjustments. A drug guide should be consulted whenever one of these drugs is added to or removed from a drug regimen. Itraconazole has a black box warning regarding the potential for serious cardio- vascular effects if it is given with simvastatin, triazolam or midazolam. These combinations should be avoided. Voriconazole and posaconazole should not be used with any other drugs that prolong the QTc interval and can cause ergotism if taken with ergot alkaloids. Box 11.2 highlights important information about hazardous interactions between voriconazole and posaconazole and the herb ergot. E chinocandin antifungals The echinocandin antifungals are another group of anti- fungals. Drugs in this class include anidulafungin and caspofungin. Therapeutic actions and indications The echinocandins work by inhibiting glucan synthesis. Glucan is an enzyme that is present in the fungal cell wall but not in human cell walls. If this enzyme is inhib- ited, the fungal cell wall cannot form, leading to death of the cell wall. See Table 11.1 for usual indications for each of these agents.

People being treated with voriconazole or posaconazole should be cautioned about the risk of ergotism if they combine this drug with ergot, a herb frequently used to treat migraine headache and menstrual problems. If the person is using voriconazole, it should be suggested that ergot not be used until the antifungal therapy is finished. Herbal and alternative therapies BOX 11.2

Safe medication administration

Name confusion has occurred between Lamisil (terbinafine) and Lamictal (lamotrigine), an antiepileptic agent. Use extreme caution if a person is receiving either of these drugs to make sure that the correct drug is being used.