There seems to be a discrepancy in dosing of Fenbendazole:(see
hsc.unm.edu/som/research/acc/drug_formulary.shtml#fenbendazole )
----- ----- cut&paste ------ -----
Fenbendazole
can, fel - 50 mg/kg PO SID x 3d
bov - 5mg/kg PO
av - 20 mg/kg PO SID x 3d.
Anthelminthic with activity against all nematodes and Taenia cestodes.
----- ----- cut&paste ------ -----
I'm reading about people taking the "dog dose" of Fenben. I'm worried that this is too much
(50mg/Kg being larger than the maximum 45mg/Kg dosage at which mice end up having
toxicity reactions to Fenbendazole). Until someone comes up with numbers indicating that
humans "clear" fenbendazole from their system at the same accelerated (high metabolism?)
rate found in dogs/cats, I would worry that people doing "dog dose" fenben are causing
themselves potential damage.
What kind of damage?
www.inchem.org/documents/jecfa/jecmono/v36je04.htmgives some examples from animal studies (the same kind of studies which would be used to justify
toxicity and teratogenicity in pharmaceutical products):
----- ----- cut&paste ------ -----
2.1.2 Fenbendazole
2.1.2.1 Long-term toxicity/carcinogenicity studies
There were no increase in tumour incidence in a 2-year
carcinogenicity study in mice with doses of fenbendazole up to
405 mg/kg bw/day (Goldenthal, 1980; Annex 1, reference 98).
A lifetime toxicity/carcinogenicity study (including an in utero
phase) of fenbendazole in Charles River CD rats used the F1
generation of pups that had been exposed to the same dose levels
in utero. Fenbendazole was fed in the diet at dose levels of 0, 5,
15, 45 or 135 mg/kg bw/day. In utero exposure to 45 mg/kg bw/day and
135 mg/kg bw/day caused severe toxicity in the pups characterized by
decreased body weights, diarrhoea, bloated stomachs, icterus and
alopecia. F1 pups exposed to 135 mg/kg bw/day had 33% decreased body
weights as compared to controls, while pups exposed to 45 mg/kg bw/day
were 15% below controls. There was also increased mortality, 18% of
pups exposed to 135 mg/kg bw/day and 14% of the pups exposed to
45 mg/kg bw/day died by day 21 of age as compared to 6% in the
controls. These data suggest that pups at 45 and 135 mg/kg bw/day had
been dosed above the MTD prior to the start of the lifetime study.
This toxicity and increased neonatal mortality severely limit the
conclusions that can be drawn from this study.
The histopathological changes observed in the liver of treated
animals were reported as hepatocellular hypertrophy, vacuolation and
bile duct proliferation in the 15, 45 and 135 mg/kg bw/day groups,
hepatocellular hyperplasia and biliary cysts in the 45 and 135 mg/kg
bw/day groups, and hepatocellular adenomas and carcinomas in the
135 mg/kg bw/day group. A group of independent pathologists reviewed
the histopathologic findings and concluded that fenbendazole treatment
did not result in an increased incidence of hepatocellular neoplasms
(Goldenthal, 1981; Lewis, 1982; Brown, 1982; Annex 1, reference 98).
2.1.2.2 Special studies on genotoxicity
The results of additional genotoxicity studies on fenbendazole
are given in Table 1.
Table 1. Results of genotoxicity studies on fenbendazole
Test system Test object Concentration Results Reference
Forward mutation Mouse up to 100 µg/ml Negative Den Boer &
assay1 lymphoma Horn, 1986
1 Both with and without rat liver S9.
Fenbendazole was assayed in L5178Y TK+/- mouse lymphoma cells
using doses ranging from 2.5 to 10 µg/ml without activation and from
4.0 to 10 µg/ml with metabolic activation. The observed toxicity
ranged from low to moderate. The substance showed steep toxicity so
that treatment in the range of 10 to 20% relative growth was not
possible. All of the treatment, both with and without metabolic
activation, induced mutation frequencies that were below the minimum
criterion of mutagenesis. The authors concluded that fenbendazole was
not mutagenic in the mouse lymphoma assay (Den Boer & Horn, 1986).
However, the test concentrations used in this study were considerably
lower than those used in the previous study when concentrations up to
62 µg/ml were tested (Cifone & Myhr, 1983).
In the opinion of independent experts, a DNA binding study would
not result in further clarification of the clastogenic effects of
fenbendazole in vitro on V79 cells, but would merely show whether
there might be an additional potential for point mutations (letter
from professor C. Schlatter, Institute for Toxicology, Zurich,
Switzerland, to Dr Müller, Hoechst AG, 1991; submitted to WHO by
Hoechst AG, Frankfurt, Germany).
Genotoxicity studies on all essential genetic endpoints gave
negative results. Clastogenic effects of benzimidazoles in vitro are
related to the inhibition of tubulin formation. In vivo assays for
binding to DNA in liver following the oral administration of
fenbendazole have not been performed.
In an expert review on the toxicology of fenbendazole, the
authors concluded that it showed no mutagenic, genotoxic or
carcinogenic potential and that sufficient data were available to
establish an ADI for fenbendazole residues in animal-derived food
(Bolt & Gansevendt, 1991).
---------------------------------
Regarding variability levels in animal dosing, please note the following from
cvm.msu.edu/extension/Rook/ROOKpdf/deworm.PDFFenbendazole
Fenbendazole is another broad-spectrum anthelmintic usually marketed under the trade name Panacur or Safe-Guard.
Fenbendazole anthelmintic preparations are designed as drenches, pastes, pellets, granules, and salt mixes carrying oral
administration approval for cattle, horses, or hogs. It is not approved for use in sheep but is safe, and is commonly used
for sheep in other countries. Fenbendazole also has a wide margin of safety, is safe for pregnant ewes, and treats all of the
major intestinal parasites that typically infect Midwestern sheep. It is effective against the common adult and larval forms
of stomach, intestinal and lung worms of sheep. It is also effective against tapeworm segments and heads but has no effect
7
on external parasites or nasal bots. Fenbendazole has minimal effects on liver flukes. Since fenbendazole preparations are
not approved for use in sheep or for use in lactating cattle, no official milk withdrawal time is listed. Slaughter withdrawal
time for cattle, however, is 8 days following administration of the drug.
Fenbendazole drench is marketed as a 10% suspension (100 mg/ml) of fenbendazole. The drench is labeled for use in
horses or cattle. Some common trade names include 10% Panacur Suspension (Horse), 10% Panacur Suspension (Cattle)
or Safe-Guard 10% Cattle Dewormer. While labeled dosing directions for horses and cattle may be different, the product
concentration (100 mg/ml) is the same.
Because fenbendazole dosing is dependent upon the parasites that are targeted, the cattle and horse products list two
different doses. Approved cattle and horse doses are labeled at either 5 mg or 10 mg of fenbendazole/kg of body weight.
These doses represent either 2.5 ml of the 10% solution per 100 lbs. of body weight (the 5-mg/kg dose) or the higher dose
of 5 ml of the 10% solution per 100 lbs. of body weight (the 10-mg/kg dose). Sheep producers commonly use the 2.5 ml
of 10% fenbendazole solution/100 lbs. of body weight dose for treating most common parasites found in sheep and increase
the dose to 5 ml/100 lbs. to increase the effectiveness on tapeworms, lungworms, and larval stages of various parasites.
Cost for treating a 150-lb. sheep would be roughly $0.45 to $0.90 per animal (dose dependent).
----- ----- cut&paste ------ -----