The effectiveness of fenbendazole as an anthelmintic in Felidae
and Ursidae is established by data from six controlled studies.
There are three studies involving 29 members of the family
Felidae and three studies involving 26 members of the family
Ursidae. The Ursidae studies involved administration of
the drug for two days. There was 100% reduction in ascarid ova
observed for some of the studies in bears while an 80% reduction of
ascarid ova was observed in one study; whereas, there was 100%
reduction in Ancylostoma and Taenia spp. ova in the
studies where they were observed. Because of the lack of substantial
adverse effects and in order to assure that bears consume an adequate
dose for ascarids, bears should be treated for three days which is the
labeled duration of treatment in the major species for which the drug
is labeled.
Critical trials in minor species are often not feasible due to obvious
difficulty in obtaining adequate numbers and the value of the animals.
Therefore, each animal served as its own control as authorized under
21 CFR 514.111(a)(5)(ii)(a)(2)(iii). The control procedure used was a
comparison of pre and post treatment parasite ova counts. Pre and post
treatment ova counts is the most appropriate control procedure
available for species included under wild Felidae and
Ursidae.
Although false positive and false negative fecal samples do occur, the
pronounced difference in pre versus post treatment values in greater
than 90% of animals tested significantly illustrates the effectiveness
of Panacur ® when administered according to label instructions.
Statistical methodology was not applied to these studies because the
animals served as their own controls and the results are obvious.
Well controlled data supporting the approval of fenbendazole in major
species (21 CFR 520.905) horses, cattle, domestic dogs and swine) have
demonstrated substantial evidence of efficacy.
A. Felidae
1. Dr. P. J. Knapmann
Six Flags Great Adventure
Jackson, N.J. 08527
A pivotal clinical field trial providing evidence for efficacy and
safety of Panacur ® was conducted on four (4) lions and seventeen
(17) Siberian tigers. Fecal samples were obtained on 4 lions and 6 of
17 Siberian tigers. The four lions were positive for Toxascaris
pre-treatment. Fenbendazole was administered at a dosage of 10
mg/kg/bw daily for three (3) days.
In the lions, there were no ova seen on day 7 post treatment, but
reappearance at day 30 post-treatment. One animal was also
positive for Toxocara at day 30.
Four of the 6 Siberian tiger samples were positive for
Toxascaris pre-treatment. All 17 animals were treated,
and fecal samples from the six animals were negative for
Toxascaris at days 7 and 30. Unspecified tapeworm segments were
noted at day 7 in two of the samples. There were no were (sic) side
effects noted.
2. Dr. William Foster
Louisville Zoological Gardens
1100 Trevilian
Way, Louisville, KY 40213
This pivotal clinical field trial providing evidence for efficacy and
safety of Panacur ® included 5 (five) Siberian tigers. They included
animals of both sexes and ranged in age from 1 1/2 years to 10 years
old. The animals weighed 250 lbs. to 400 lbs. Pre-treatment
fecal examination revealed the presence of ascarid spp.
Treatment of the tigers with a dose of 10 mg/kg/bw (one animal
received 13.3 mg/kg) daily for three days resulted in total reduction
of ova shedding at days 7 and 14 post-treatment. There were no
adverse reactions noted.
3. Mr. Gerald Brady
Bear Country, U.S.A.
Rapid City, S.D. 57709
This pivotal clinical field trial providing evidence of efficacy and
safety of Panacur ® included 13 (thirteen) pumas. Pre-treatment
fecal examinations of six of the pumas revealed the presence of ova
from Toxocara, Toxascaris, Ancylostoma, and
Taenia spp. Treatment with Panacur ® at 10 mg/kg/bw daily for
three (3) days resulted in total elimination of ova shedding at day 7
post-treatment for Toxocara, Toxascaris, and
Taenia. There was one animal positive for Ancylostoma
spp. pre-treatment and one animal positive for
Ancylostoma spp. post-treatment. All but two of the
animals took the drug without hesitation. There were several reports
of loose stools among the pumas ingesting the Panacur ® granules.
B. Ursidae
1. Mr. Gerald Brady
M.S. Bear Country U.S.A.
Rapid City, S.D. 57709
This pivotal clinical field trial providing evidence of efficacy and
safety of Panacur ® consisted of 105 (one hundred five) bears of
which 20 (twenty) had pre-treatment fecal exams examined for
parasite ova. Sixteen of the twenty were positive for ascarids,
Ancylostoma, and/or Taenia spp.. The bears were
treated with Panacur ® orally at a dose level of 10 mg/kg/bw daily for two days.
Results demonstrated a 100% reduction in ova shedding for
Ancylostoma and Taenia spp. and 80% reduction in ascarid
ova. All but two animals took the drug without hesitation. There were
several reports of loose stools among the bears ingesting the
Panacur ® granules.
2. Dr. P. J. Knapmann
Six Flags Great Adventure
Jackson, N.J. 08527
This pivotal clinical field trial providing evidence of efficacy and
safety of Panacur ® consisted of seven (7) brown bears. Fecal counts
were conducted on seven animals and three were positive for ascarids
and one for Ancylostoma spp. ova. Treatment consisted of fenbendazole
administered at a rate of 10 mg/kg/bw daily for two consecutive days.
This treatment resulted in 100% negative stools at 7 and 30 days post-
treatment. There were no reported adverse effects.
3. Dr. William Foster
Louisville Zoological Gardens
Louisville, KY 40213
This pivotal clinical field trial providing evidence of efficacy and
safety of Panacur ® included two female and one male 7 and 8 year old
polar bears weighing 400 lbs to 600 lbs, which were diagnosed via pre-
treatment fecal exams as having ascarid spp. Treatment consisted
of administering Panacur ® granules at 10 mg/kg/bw daily for two
days. Results, as measured by detection of ova shedding, indicate that
the drug was 100% effective at 7 and 14 days post treatment.
Corroborative Studies
1. Dr. William Foster
Louisville, Zoological Gardens
1100 Trevilian Way
Louisville, KY 40213
This corroborates field trial included one male and one female
cheetah, both 5 years old and weighing 80 lbs to 85 lbs, which showed
evidence of Toxascaris ova on pretreatment fecal examination.
They were treated with 6.5 mg/kg/bw for one day and did not show
evidence of ova shedding when feces were examined on days 7 and 14.
There were no reports of adverse effects.
2. Professor K. Enigk
Parasitology Institute
University of Hannover
W. Germany
This corroborative field trial involved sixty-six (66) animals
including 25 lions, 20 tigers, 10 pumas, 4 leopards, 1 black panther,
and 6 jaguars. A dose level of 10 mg/kg/bw for one treatment proved to
be effective in the above species against Toxascaris spp. This
level did not provide acceptable efficacy against Toxocara or
Ancylostoma spp. Ten mg/kg/bw daily for three (3) days provided
100% reduction in Toxocara, Toxascaris, and
Ancylostoma spp. infections in the 11 tigers dosed for that
time period.
3. Dr. D. C. Hall
Vilas Park Zoo
Madison, Wisconsin 53715
The corroborative study involved one polar bear (weighing 797 lbs) and
two grizzly bears (weighing 175 lbs). Pre-treatment fecal
examination of the polar bear and one grizzly bear was positive for
ascarid shedding. Animals were dosed at a level of 10 mg/kg/bw daily
for two days. Post treatment fecal examination of the polar bear was
negative at days 7, 14, and 21. The grizzly bear continued to shed
diminishing numbers of ova on days 7 and 14, and becoming negative at
day 21.
Efficacy Summary Statement
Efficacy studies submitted to support the use of Panacur ® granules
in wild Felidae and Ursidae were conducted using fecal
egg counts to monitor effectiveness. The traditional controlled
efficacy study (where animals are sacrificed and worms are counted)
could not be used in these studies due to the rarity and high value of
the animals. Parasites were often only identified to the genus level
(and sometimes only to order level, i.e. ascarids) from egg
identification following fecal examination. This was done because of
the relative host specificity and likelihood of helminth species
affecting wild Felidae and Ursidae. Based on the
following references, the species that would be expected to be found
in wild Felidae and Ursidae and against which Panacur ®
would expect to have efficacy based on the studies conducted, are used
in the label indications.
Felidae
For ascarid species in Felidae Toxocara cati and
Toxascaris leonina are both common and either or both species
could be present in animals at any location or from any sources
(Soulsby).
The identification of Taenia spp. is used based on the fact
that one of several species may be present, and the actual
distribution of different species in wild Felidae has not been
fully delineated. Identification of species by egg examination is
impossible.
For hookworm species, Ancylostoma tubaeforme, A.
braziliense, A. paraduodenale or A. ceylanicum may
be present depending on geographic location of the zoo or the
source of the animal (Soulsby). The eggs of these species cannot be
distinguished from one another; therefore, the designation of
Ancylostoma spp. is given on the label. This is also the
designation used by Fowler (see reference).
Ursidae
In Ursidae, the most common ascarid species is Baylisascaris
transfuga, being nearly ubiquitous (Soulsby, Pence et al).
Toxascaris leonina, might be expected from black bears in
southern coastal regions (Pence et al, Crum et al).
Pence et al identified two species of Taenia, T.
hydatigena and T. krabbei. However, the researchers
indicated that species identification was not always possible and
groups these (and any other possible species) together as
Taenia spp.
The hookworm species that has been identified in the black bear is
A. caninum (Pence et al, Crum et al) which is found in southern
regions.
References
Helminths, Arthropods and Protozoa of Domesticated Animals,
E.J.L. Soulsby, 7th Edition, Lea & Febiger, Philadelphia, 1982, pp.
149, 150, 152, 199, 200.
Zoo and Wildlife Animal Medicine, M.E. Fowler, 1st edition and
2nd edition, W.B. Saunders Company, Philadelphia, 1978, pp. 615 and
1986, pp. 837-838.
Ecological Analyses of Helminth Populations in the Black Bear,
Ursus americanus, from North America. D.B. Pence, J.M. Drum and
J.A. Conti. Journal of Parasitology, 69(5) 1983, pp. 933-950.
Studies on Endoparasites of the Black Bear (Ursus americanus)
in the Southeastern United States. J.M. Crum, V.F. Nettles, W.R.
Davidson. Journal of Wildlife Diseases, 14(April), 1978, pp.
178-186.
1. Dr. William Foster
Louisville Zoological Garden
Louisville, KY 40213
This study was a pivotal toxicity study providing information
supporting the safety of Panacur ® granules in members of the
families Felidae and Ursidae. Five big cats, including
two jaguars, one puma, one lion, and one Siberian tiger representing
both sexes and ranging in age from 2 to 15 years of age were dosed
with the drug. Additionally, three polar bears ranging in age from 7
to 9 years of age and representing both sexes were dosed with 100
mg/kg/bw of the drug for four (4) days. The Felidae were dosed
with 100 mg/kg/bw for six (6) days.
In one jaguar and the lion, there were periods of inappentence (sic)
following the initial consumption of fenbendazole at ten times the
recommended level. It is noted that the ambient temperature at the zoo
during this study was higher than normal; therefore, the role of the
extreme heat on appetite can be considered.
Large cats offered 5X the dose for twice the duration and polar bears
dosed at 10X the dose for 1.33 times the duration provides evidence
that at exaggerated doses for greater than the indicated duration, the
drug is not associated with adverse reactions. The only remarkable
finding is that the overdosed animal may not consume the drug.
Due to the nature of the study, safety parameters were limited to
those which could be obtained from clinical observation of the
animals. Necropsies were not necessary nor feasible because of the
absence of adverse effects and the value of the animals.
Traditional clinical (laboratory) target animal toxicity studies would
ordinarily not be feasible for rare, exotic, or endangered wildlife
species. It is concluded that the safety of Panacur ® granules in
members of the families Felidae and Ursidae is
demonstrated under actual conditions of use in clinical field trials
(see "Effectiveness" section).
The margin of safety is demonstrated in a limited number of animals
which are dosed with ten (10) times the recommended amount of the
Panacur ® granules for up to twice the recommended duration. The
nature of the animals being studied necessitated avoidance of
unacceptable or irreversible adverse reactions.
