Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 15 CANCER CHEMOTHERAPY
concentrations; consequently, it is typically recommended
to dilute the drug in 0.9% sodium chloride and
infuse over 30–60 min or to inject the solution into the
side port of a fast-running IV saline drip over 30–60 min
to minimize toxic side effects. Slower infusion rates also
result in a greater area under the curve and a longer
distribution phase than a faster infusion rate. Drug
clearance is positively correlated with infusion rate.
Doxorubicin is metabolized in the liver and excreted in
the bile. In the dog, only 3% of the drug is excreted in
the urine.
Adverse effects
● The most common signs of doxorubicin toxicosis in
both the dog and cat are gastrointestinal – vomiting,
diarrhea, colitis, anorexia and weight loss. These
usually occur 3–5 d following treatment.
● Administration of doxorubicin has been shown to
cause a dose-related increase of peripheral tissue histamine
release and a secondary increase in catecholamine
release. Clinical signs attributed to histamine
release are pruritus, head shaking, urticaria, erythema
and vomiting. Some oncologists recommend
premedication with diphenhydramine in dogs or
short-acting glucocorticoids in cats. These effects
have been reported to be more frequent when a
generic formulation of the drug is used.
● Clinically significant myelosuppression is uncommon
in dogs given a standard dose of doxorubicin as a
single agent. Dogs receiving doxorubicin in a multidrug
protocol may experience severe myelosuppression.
The nadir of neutropenia occurs 7–10 d
post-treatment. In cats the nadir of neutropenia
occurs between days 8 and 11 after treatment. RBC
poikilocytosis occurs in cats following administration
of doxorubicin but is clinically insignificant and
not associated with anemia.
● Alopecia and hyperpigmentation of the skin occur in
some dog breeds, especially poodles, old English
sheepdogs and terriers. Dogs with long hair on the
tail or legs (e.g. golden retrievers) lose the long hairs
but not the entire coat. Cats receiving doxorubicin
lose whiskers but loss of the entire hair coat is rare.
These consequences of doxorubicin administration
are insignificant to the patient but can be significant
to the owners and should be discussed prior to drug
administration.
● Doxorubicin-induced cardiomyopathy limits the
total cumulative dose that can be administered in the
dog (