Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

AVERMECTINS
● Administration of some MLs to microfilaria-positive
dogs has also been associated with adverse effects,
generally milder than those encountered with the use
of DEC, although deaths have been reported.
Resistance
Resistance has not yet been reported among the parasites
of dogs and cats but is widely encountered in
endoparasites of ruminants, including sheep, goats and
cattle.
Resistance to both avermectins (ivermectin) and
milbemycins (moxidectin) is reduced by administration
of the calcium channel inhibitor verapamil, indicating
that at least one mechanism involves active drug efflux
out of target parasites by the drug transporter
P-glycoprotein.
Precautions
● Use in collies and other breeds with reduced or
absent P-glycoprotein activity.
● Use in microfilaremic dogs.
● Missed doses in heartworm prevention.
AVERMECTINS
Ivermectin
22,23-dihydro-avermectin B 1a ; 22,23-dihydroavermectin
B 1b .
Ivermectin contains at least 80% 22,23-dihydroavermectin
B 1a and not more than 20% 22,23-dihydroavermectin
B 1b and was first commercialized in 1981.
Pharmacokinetics
Ivermectin is absorbed rapidly after oral administration
of tablets or chewable dosage forms, with peak plasma
concentrations noted at 4–10 h. Maximum concentrations
increase in direct proportion to dose, indicating a
linear relationship between dose and bioavailability.
The drug is widely distributed, with a V d of 2.4 L/kg,
and is eliminated with a half-life of approximately 1.8
days. Similar pharmacokinetics are present in the cat,
with T max reported to be 5.5 h and no detectable ivermectin
by day 5 after treatment.
Extra-label applications (not for sensitive dogs
including collies)
D. immitis microfi laria 0.050 mg/kg
96% of 121 dogs became
amicrofi laremic after a single dose
(90% within 3 weeks) and the
remainder after repeated doses.
Sarcoptes scabiei
0.2–0.3 mg/kg PO, SC
Otodectes cynotis
Demodex canis (repeated every
2–3 weeks)
Pneumonyssoides
Eucoleus and Pearsonema
(Capillaria ) spp
T. vulpis
T. canis (not T. leonina)
A. caninum
A. braziliense
U. stenocephala
Angiostrongylus vasorum
Physaloptera rara
D. reconditium
T. canis prevention of transmission 0.3 mg/kg SC to
to puppies
pregnant bitches on
gestation days 0, 30,
60 and postgestation
day 10
Demodex canis
0.3–0.6 mg/kg PO daily
for 2 months
Filaroides osleri (repeated every 0.4 mg/kg
2 weeks)
CATS
D. immitis precardiac stages 0.024 mg/kg PO monthly
A. tubaeforme
A. braziliense
Sarcoptes
0.2–0.4 mg/kg PO, SC
Notoedres
Otodectes
T. cati 0.3 mg/kg SC
Cheyletiella spp
Lynxacarus radovskyi
Aelurostrongylus abstrusus
0.4 mg/kg SC
#
Heartworm adulticidal activity of monthly ivermectin has
been associated with deterioration of radiographic signs
and should be applied carefully and with appropriate
monitoring in symptomatic and asymptomatic dogs.
Clinical applications and dose rates
DOGS
D. immitis precardiac stages 0.006 mg/kg PO monthly
D. immitis adults after repeated
monthly treatments #
Adverse effects
Dogs
● The acute oral LD 50 of ivermectin in beagles is 80 mg/
kg and the highest no-effect dose is 2 mg/kg with
single doses and 0.5 mg/kg for daily doses for 14
days.
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