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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.
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.
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
