Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

DRUGS WITH IMMUNOSTIMULATORY EFFECTS
stimulating factor (GM-CSF). rHuGM-CSF induces
neutrophilia, monocytosis, eosinophilia and thrombocytopenia
in normal dogs and can ameliorate the effects
of total body irradiation on bone marrow hematopoiesis.
rCaGM-CSF has similar effects on leukocyte and
platelet numbers in normal dogs but is less effective than
the human product in counteracting the bone marrow
effects of total body irradiation.
Interferon-α
A number of studies have examined the potential benefit
of administration of rHuIFN-α (Roferon®) to cats. In
one study of experimental FeLV infection, oral administration
(generally given at 30 U/cat q.24 h on a 1-
week-on, 1-week-off cycle) was shown to ameliorate
the clinical course of disease (but not viremia) and there
are anecdotal reports of efficacy in managing the
clinical effects of spontaneously arising FeLV, FIV
and FIP infections. It is presumed that the agent has a
localized effect on oropharyngeal lymphoid tissue, as
there is poor systemic absorption following oral
administration.
rHuIFN-α has also been administered SC at high dose
(10 U/kg q.24 h for 8 d, then alternate days for another
2–3 weeks) to cats experimentally infected with FIP
virus. Treated cats had suppression of clinical signs and
serum antibody levels, with a small increase in survival
times. Similar beneficial effects were reported in FeLVinfected
cats given combined rHuIFN-α and AZT.
As for other human recombinant products, neutralizing
antibodies are induced after several weeks (with
SC but not oral therapy) and the cats become refractory
to therapy.
Interferon-ω
Interferon-ω is a type I interferon that is related to
interferon-α. A recombinant version of feline interferonω
has been produced commercially (Virbagen Omega®,
Virbac Ltd) and is licensed in Europe for specific indications
in the dog and cat.
Clinical applications
Virbagen Omega® is licensed for therapeutic use in
dogs (over 1 month of age) with enteric parvovirus
infection and is claimed to be able to reduce mortality
and clinical signs in such cases. In the cat, Virbagen
Omega® is licensed for the treatment of FeLV and FIV
infections. When administered to cats during the symptomatic
(but nonterminal phase) of these infections, the
product claims to reduce the clinical signs and mortality
associated with infection. Although not licensed for
other applications, the use of Virbagen Omega® has
been investigated in cats with upper respiratory tract
calicivirus infection (and chronic gingivostomatitis),
herpesvirus infection (and keratoconjunctivitis) or feline
infectious peritonitis virus infection. The use of this
product has also been examined in noninfectious disease
(e.g. canine atopic dermatitis) but no clear benefits have
been proven.
Mechanism of action
The precise mode of action of Virbagen Omega® is not
described but in general, type I interferons bind to
surface receptors expressed by a range of cells (both
virally infected and noninfected) and trigger an intracellular
signaling pathway resulting in gene transcription
of host cell proteins that inhibit viral replication within
infected cells, upregulate expression of molecules
involved in antigen presentation (class I molecules of the
major histocompatibility complex) and activate NK
cells to destroy virally infected cells through cytotoxic
mechanisms.
Formulations and dose rates
Virbagen Omega® comes as a vial containing 10 million units (MU)
of lyophilized recombinant interferon-ω. Solvent for resuspension of
the lyophilizate into a 1 mL volume is provided. For dogs with parvoviral
enteritis, a dose of 2.5 MU/kg is injected intravenously each day
for 3 d. For cats with retroviral infection, a dose of 1 MU/kg is injected
subcutaneously once daily (starting on day 0) for d. This 5-d treatment
is then repeated from day 14 and again from day 60.
Adverse effects
● Transient hyperthermia 3–6 h after injection.
● Vomiting.
● Mild leukopenia, thrombocytopenia and anemia
that revert to normal within 1 week after the last
injection.
● Mild elevation in alanine aminotransferase that
reverts to normal within 1 week after the last
injection.
● Soft feces to mild diarrhea in cats only.
● Transient fatigue during treatment in cats only.
Animals receiving Virbagen Omega® should not be
vaccinated during or after therapy until the animal is
clinically normal. The safety of the agent has not been
established in pregnant or lactating animals. In humans
treated with multiple doses of type I interferon, autoimmune
diseases have occasionally been recognized. This
has not yet been reported in animals but remains a
consideration. If this product is administered intravenously
to cats there is a greater frequency of adverse
effects (including hyperthermia, soft feces, anorexia,
decreased drinking and collapse).
Known drug interactions
There is no specific information available on drug interactions.
Animals treated with this product are likely to
283