I. GENERAL INFORMATION:
| NADA |
139-189 |
| Sponsor: |
Hoechst-Roussel Agri-Vet Company
Route 202-206 North
Somerville, New Jersey 08876 |
| Generic Name: |
Fenbendazole
|
| Trade Name: |
SAFE-GUARD® |
| Marketing Status: |
Over-the-counter
(OTC |
| Notes: |
The
original approval provided for a 25 lb. medicated molasses block containing
750 milligrams of fenbendazole per pound as a beef cattle anthelmintic.
The molasses block requires an 11-day withdrawal. This supplemental approval
provides for a 33-1/2 pound cold press medicated 20% protein feedblock
containing 750 milligrams of fenbendazole per pound as a beef cattle anthelmintic.
The cold press 20% protein block requires a 16-day withdrawal period. |
II. INDICATIONS FOR USE
Cattle dewormer for the removal
and control of:
Lungworm: (Dictyocaulus viviparus
).
Stomach worms: Barberpole worm
(Haemonchus contortus), Brown stomach worm (Ostertagia ostertagi ),
Small stomach worm (Trichostrongylus axei ).
Intestinal worms: Hookworm (Bunostomum
phlebotomum ), Threadnecked intestinal worm (Nematodirus helvetianus
), Small intestinal worms (Cooperia oncophora and C. punctata
), Bankrupt worm (Trichostrongylus colubriformis ), Nodular worm
(Oesophagostomum radiatum ).
III.
DOSAGE
| A. |
DOSAGE FORM |
20%
Natural Protein deworming supplement (cold press) feedblock for beef cattle.
This cold press feedblock is manufactured by V.M.S., Inc. Montgomery,
AL. Each feedblock weighs 33.5 pounds and contains 730 mg fenbendazole
per pound. |
| B. |
ROUTE OF ADMINISTRATION |
The
feedblock label contains complete directions for administration. |
| C. |
RECOMMENDED DOSAGES: |
1.67
mg fenbendazole per kg of body weight per day , for three (3) days. Total
dose for the 3 day period of 5 mg/enbendazole per kg of body weight (2.27
mg fenbendazole per pound). |
| |
|
|
IV.
EFFECTIVENESS
This NADA relies on adequate well
controlled studies showing the anthelmintic efficacy of fenbendazole in cattle
included in the approved NADA 128-620 (Fenbendazole Suspension 10%, 48 FR 42809,
September 20, 1983). The original NADA (128-620) provided for a dose of 3 mg
fenbendazole/kg of body weight administered in a one (1) day treatment. This
NADA demonstrates that the 5 mg dose given over a three (3) day period is equally
as efficacious.
One study was conducted in cattle
to demonstrate that the efficacy of fenbendazole in the feedblock formulation
is equal to the suspension formulation when used at the same dose of 5 mg fenbendazole/kg
body weight. It is appropriate to conclude that the feedblock formulation is
equally efficacious.
Efficacy and consumption was demonstrated
in these studies:
Efficacy Evaluation of Feedblocks
Medicated with Fenbendazole
M. Blagburn, Auburn University,
Auburn, Alabama
Twenty cattle naturally infected
with gastrointestinal nematodes were identified and assigned to two groups of
ten cattle each. One group remained unmedicated and one group was given fenbendazole
via the natural protein cold press feedblock at a dose of 5 mg fenbendazole
per kg of body weight over a 3 day period. Adequate numbers of parasites were
recovered from the control animals at postmortem to evaluate and compare the
effect of the feedblock formulation on the following species:
(Eds. note: The following table
consists of 2 columns.)
% Reduction
H. contortus 100
O. ostertagi 99.9
C. punctata 100
O. radiatum 100
T. axei 100
Consumption rate by cattle of feedblocks
containing Fenbendazole
Four feedblock consumption studies
were conducted. The total number of mature cattle utilized for these studies
was 195 head tested using the cold press feedblock. The studies were conducted
in Alabama, Louisiana and Wyoming. To achieve the desired level of fenbendazole
medicated block consumption, cattle require a period of time for adaptation
to feedblocks. This adaptation period varied depending upon current and previous
herd feeding and husbandry practices in addition to weather conditions. From
these studies, it was determined that specific medicated block treatment can
be administered after 12-19 days adaptation period with non-medicated feedblocks.
The medicated feedblocks were given
for a 3 day treatment period with the total fenbendazole consumption for the
3 day period calculated to be 5 mg fenbendazole/kg of body weight. The actual
average consumption rate for fenbendazole averaged across the 3 locations was
4.55 (± 0.88) mg fenbendazole/kg body weight for the cold press blocks
(see the following table).
(Eds. note: The following table
consists of 2 columns.)
AVERAGE FENBENDAZOLE CONSUMPTION
CALCULATED FOR EACH LOCATION
Cold Press Blocks - Consumption Averages
Per Capita FBZ (mg/kg)
Wyoming 5.45
Louisiana 5.02
Alabama, Group 1 4.88
Alabama
Study 11, Group 1 3.19
Alabama
Study 11, Group 2 4.23
Average 4.55
Std. Deviation 0.88
These studies were conducted by:
Dr. Dean Danilson, Asst. Prof.
Auburn University
Auburn, AL. 36849-4201
Dr. Gene Luther
Dept. of Vet. Science
Louisiana State University
Baton Rouge, LA. 70803-6002
Dr. J. Waggoner Jr.
University of Wyoming
Dept. of Animal Science
Laramie, WY. 82071
The consumption and efficacy studies
confirm that the feedblock formulation is efficacious when the total dose of
5 mg fenbendazole per kg body weight is given over a 3 day period.
The recommended treatment was found
to be both safe and practical under field conditions.
V. ANIMAL SAFETY
This NADA relies on safety studies
included in the approved NADA 128-620 (Fenbendazole Suspension 10%, 48 FR 42809,
September 20, 1983), that indicated the maximum tolerance dose is greater than
2000 mg fenbendazole/kg body weight.
Therefore, as predicted, no visible
adverse reactions were observed in any of the laboratory efficacy or clinical
field trials conducted in cattle with cold press feedblocks containing fenbendazole.
VI. HUMAN SAFETY:
a. Safe Concentration of Residues
The safe concentration for total
fenbendazole residues in the uncooked edible tissues of cattle were established,
based upon toxicology studies submitted under NADA 128-620 (48 FR 42809-9/20/83)
as 5 ppm in muscle, 10 ppm in liver, 15 ppm in kidney and 20 ppm in fat.
b. Metabolism Studies
Under NADA 128-620 metabolism studies
in cattle were conducted to select a marker substance and target tissue for
fenbendazole. Cattle liver is the target tissue with parent fenbendazole being
the marker substance. The tolerance (Rm) is 0.8 ppm parent fenbendazole for
cattle receiving a single oral dose of 10 mg fenbendazole/kg BW, i.e. when total
fenbendazole residues are 10 ppm in liver, there is 0.8 ppm parent fenbendazole
as determined by the regulatory method. Acceptable comparative metabolism studies
were described under NADA 128-620.
c. Regulatory Method
Under NADA 128-620, the method
was developed for the determination of parent fenbendazole at the tolerance
of 0.8 ppm concentration in cattle liver.
d. Withdrawal Time
Under NADA 128-620 (suspension
10%) it was determined that a withdrawal time of 8 days is necessary for the
residues of fenbendazole to deplete to sale concentrations in all tissues.
Under this NADA a residue depletion
study using the approved analytical method was conducted to determine when residues
of the feedblock formulation deplete to or below the established safe concentration.
Twenty eight cattle were treated
orally over a 3 day period with the feedblock formulation to provide a total
dose of 10 mg fenbendazole/kg of body weight.
A statistical analysis using CVM's
99% tolerance limit with a 95% confidence interval on the data in the following
table determined that fenbendazole residues were below the tolerance of 0.8
ppm 16 days after the end of the treatment period. The projected residue level
at the end of a sixteen (16) day withdrawal period was 0.74 ppm. The Agency
has reviewed the residue data and has concluded that this supplement will not
alter the concentration and qualitative composition of the residue.
(Eds. note: The following table
consists of 2 columns.)
FENBENDAZOLE RESIDUES IN CATTLE LIVER AFTER A
THREE DAY TREATMENT PERIOD USING THE COLD PRESS
FEEDBLOCK FORMULATION WITH A TOTAL DOSE OF 10 MG
FENBENDAZOLE PER KG OF BODY WEIGHT
Sacrifice Date
after Treatment PPM Fenbendazole(l,2)
1 day 14.56 (±16.62)
3 days 13.75 (±17.06)
5 days 3.92 (±5.37)
7 days 1.67 (±2.52)
1 Values are the average from seven (7) animals per data point.
2 Standard deviation in ( ).
Therefore, it has been established
that 16 days after treatment with a three day oral dose of 10 mg fenbendazole/kg
b.w. in the cold press feedblock formulation is sufficient to confirm that no
residues are present that may be harmful to human health.
e. Safety to Handler
Under NADA 128-620, studies were
conducted which demonstrated that the drug would have no ill effects on persons
handling it if the drug is used according to label recommendations.
VII.
AGENCY CONCLUSIONS:
This is a supplemental approval.
NADA 139-189 provides for a 25 pound molasses block having 750 mg fenbendazole/pound.
The supplement is for a cold press protein block of 33-1/2 pounds having 750
mg fenbendazole/pound. The data submitted in support of this NADA comply with
the requirements of section 512 of the Act and demonstrates that fenbendazole
(Safe-Guard) in a 20% natural protein deworming (cold press) feedblock when
used under its proposed condition of use is safe and effective for the removal
and control of lungworms, stomach worms and intestinal worms in cattle.
The Agency concludes that adequate
directions for use have been written for the proposed over-the-counter use of
this broad spectrum anthelmintic which is indicated for the removal and control
of parasites commonly occuring in cattle. Fenbendazole premixes in swine and
fenbendazole suspension, paste, and feedblock (containing molasses) in cattle
are presently marketed over-the-counter as broad spectrum anthelmintic drug
products. Fenbendazole medicated feedblock is currently codified in section
21 CFR 520.905e for use in cattle providing for the same concentration (750
mg/lb) and conditions of use with the exception of the drug withdrawal requirements
(11 days for the molasses-containing block and 16 days for the cold press block).
The Agency has reviewed the residue data and has concluded that this supplement
will not alter the concentration and qualitative composition of the residue.
Therefore, this supplement will pose no increased human risk from exposure to
the drug.
Under the Center's supplemental
approval policy (42 FR 64367), this is a Category II change which provides for
an additional feed block formulation. This change is not expected to adversely
affect the safety and effectiveness of the drug. Therefore, this action did
not require a reevaluation of the underlying safety and effectiveness data in
the parent application.
VIII. LABELING (Attached)
1. SAFE-GUARD® (fenbendazole)
product label
Copies of this label may be obtained
by writing to the:
Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857
Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.
