Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 9 SYSTEMIC ANTIFUNGAL THERAPY
treatment of choice for blastomycosis and most other
systemic mycoses in dogs. Itraconazole has proved very
effective as a sole treatment agent for histoplasmosis in
cats. It has historically been an important treatment for
systemic aspergillosis in humans, but has not proved
to be very effective in dogs and cats for this purpose.
We have found high-dose itraconazole combined with
terbinafine to be variably effective in treating dogs with
pythiosis, despite the fact that Pythium insidiosum does
not contain significant concentrations of membrane
ergosterol.
When treating most systemic fungal infections, there
is a lag between the initiation of treatment and clinical
improvement. In severely affected animals consideration
should be given to the concurrent administration of
amphotericin B and itraconazole, especially during this
lag period. Itraconazole is a less toxic, more efficacious
alternative to griseofulvin for treating dermatophytes
and to potassium iodide for treating sporotrichosis.
Formulations and dose rates
DOGS
• 5–10 mg/kg PO or IV q.24 h
• Dogs with blastomycosis should be treated with 5 mg/kg as
there is no added benefi t to increasing the dose and side
effects are dose dependent. Dogs with other systemic fungal
infections may require 10 mg/kg
CATS
• 10 mg/kg PO or IV q.24 h
• Anorexia and gastrointestinal side effects are less apparent
when the dose is divided into two daily doses
Pharmacokinetics
Pharmacokinetic studies in healthy humans and cats
have demonstrated increased absorption of itraconazole
after administration of the oral solution in comparison
to capsules. Concentrations of itraconazole are typically
low in urine and CSF and it does not cross the blood–
brain, blood–prostate or blood–ocular barrier well.
However, despite this fact, fungal infections involving
the CNS, prostate or eye often respond well to itraconazole
therapy, perhaps because its liphophilicity allows
even small amounts of the drug that move across
inflamed barriers to accumulate in these lipid-laden
tissues.
Adverse effects
Dose-related local ulcerative dermatitis, caused by a
cutaneous vasculitis, is seen in approximately 5–10% of
dogs given high (10 mg/kg) oral doses of itraconazole.
When recognized early, the vasculitis usually resolves
shortly after the drug is discontinued and rarely recurs
if lower doses are reinstituted. If not recognized early,
however, the vasculitis can result in catastrophic cutaneous
and subcutaneous necrosis and sloughing.
Fluconazole
Clinical applications
Fluconazole can be used similarly to itraconazole
although it appears to be slightly less efficacious for
many systemic fungal infections. The drug’s metabolism
and its low lipophilicity and small molecular size may
allow increased drug concentrations and efficacy in the
management of central nervous system, prostatic and
urinary tract infections. However, controlled studies in
humans do not indicate a major advantage. Fluconazole
appears to be the treatment of choice for cryptococcosis.
The marketing of a generic formulation of fluconazole
in the USA has substantially reduced the cost of treatment,
making fluconazole the most cost-effective antifungal
agent in many circumstances.
Formulations and dose rates
DOGS
• 2.5–10 mg/kg PO or IV q.24 h
CATS
• 10 mg/kg PO or IV q.24 h
• 50 mg/cat < 3.2 kg, 100 mg/cat > 3.2 kg for cryptococcosis
Clotrimazole
Clotrimazole is one of the oldest imidazole antifungal
drugs.
Clinical application
Clotrimazole has proved to be very effective as an intranasal
infusion in the treatment of nasal aspergillosis.
Formulations and dose rates
Clotrimazole has very poor oral bioavailability and is thus used as a
topical preparation. A 1% solution of clotrimazole in polyethylene
glycol is infused through the nares into the nasal cavity and nasal
sinuses. A large Foley catheter is used to occlude the internal nasal
choanae by placing the balloon of the catheter into the nasopharynx
in a retrograde manner via the oral cavity. Two smaller Foley catheters
can be used to occlude the external nares. The drug is infused into
the nasal cavity (60 mL per side in medium to large-breed dogs) of
the anesthetized patient and allowed to sit for 1 h. Rotating the head
after each 15 min has been recommended to enhance drug
distribution.
A 1% solution in propylene glycol is available commercially.
Although used safely in many cases, this preparation has been implicated
in the induction of pharyngeal infl ammation and edema in one
dog that developed upper airway obstruction. However, other factors
associated with case management probably contributed.
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