Summary of
FDA Information:
Approval Date: September 26, 1988
Freedom of
Information Summary
NADA 139-633
I. GENERAL INFORMATION:
NADA 139-633
Sponsor: Wildlife Laboratories, Incorporated
1401 Duff Drive, Suite 600
Fort Collins, Colorado 80524
Generic Name: Carfentanil Citrate
Trade Name: WILDNIL
Marketing Status: Prescription (Rx)
II. INDICATIONS FOR USE
For use as an immobilizing agent in free-ranging or
confined members of
the family Cervidae (deer, elk, moose).
III. DOSAGE FORM(S), ROUTE OF ADMINISTRATION AND RECOMMENDED DOSAGE
The product is supplied as a sterile solution for
parenteral administration into
a large muscle mass at a dosage ranging from
0.005 to 0.020 milligrams per kilogram of
body weight.
IV. EFFECTIVENESS
The efficacy of
Carfentanil as an immobilizing agent for
members of
Cervidae family has been demonstrated in 19 well controlled pivotal and
corroborative clinical field trials conducted with 158 moose, 295 elk, 18 Axis deer, 9 Sika deer and
29 exotic Cervidae.
Due to the readily observable effect (immobilization), each animal served as its own control as provided under
21 CFR 514.111(a)(5)(ii)(a)(2)(iii).
A summary of
the data follows.
A . Studies in Moose
1. Study One in Moose
Type of
Study: Field study
.
Name and
Address of
Investigator:
Dr. Albert W. Franzmann
Alaska Department of
Fish & Game
Soldotna, Alaska
Study Design:
Purpose: Evaluation of
Carfentanil as an immobilization agent for
moose with antagonism by diprenorphine.
Test Animals:
1) Number: 92
2) Age and
Sex: Adults of
both sexes
3) Free-ranging moose.
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: Not applicable
Dose Forms:
Injectable liquid. Active chemical and
vehicle are identical to formulation for
which approval is requested.
Route of
Administration: Intramuscular
Dosage Used: 0.006 to 0.014 mg/kg body weight
Test Duration: 12 months, March 1983 to March 1984
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
Total dosage per moose varied from
2.5 to 5 mg Carfentanil (0.006 to 0.014 mg/kg). Mean induction time for
moose receiving at least 3 mg was
5.0 minutes. Diprenorphine was
used as the antagonist. During 1983, the
dosage used was
14 mg IV and
6 mg IM. In 1984, the
antagonist dosage was
increased and
20 mg were
given IV and
10 to 20 mg IM. Mean recovery time was
4.2 minutes. Hyperthermia, acute capture myopathy and
/or narcotic recycling were
attributed to 6 mortalities (6.5%) directly associated with immobilization.
Statistical Analysis: None conducted.
Conclusions:
The data gathered during this study
show that Carfentanil citrate administered at dose ranges of
0.006 - 0.014 mg/kg body weight intramuscularly to moose produces rapid immobilization and
that the
immobilization may be reversed by diprenorphine at a total dose range of
20 to 40 mg per moose.
Adverse Reactions:
Six mortalities were
observed (6.5%) some of
which
may have been treatment related.
These were
a result of
hyperthermia, acute capture myopathy and
narcotic recycling.
Special Issues: None
2. Study Two in Moose
Type of
Study: Field Study
Names and
Addresses of
Investigators:
Mr. John Kimball
Utah Game & Fish Department
Ogden, Utah
Dr. Ted Stanley
Department of
Anesthesiology
University of
Utah Medical Center
Salt Lake City, Utah
Study Design:
Purpose: Evaluation of
Carfentanil as an immobilization agent for
moose.
Test Animals:
1) Species Used: Moose (Alces alces)
2) Number: 9
3) Age: 4 adults, 4 calves and
1 yearling
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Forms: Injectable liquid.
Route of
Administration: Intramuscular
Dosages Used: 0.006 - 0.015 mg/kg body weight
Test Duration: N/A
Parameters Measured:
1) Dose administered
2) Time to immobilization
3) Amount of
antagonist
4) Time to recovery
5) Adverse effects
Results: Mr. Kimball, Regional Biologist for
Utah Game and
Fish utilized Carfentanil under
"real world" situations to rapidly immobilize and
remove moose in situations were
they had locked antlers or
had wandered near towns. Seven of
the 9 moose that were
immobilized were
reversed with Diprenorphine at a ratio of
approximately 7 mg of
Diprenorphine per 1 mg Carfentanil. One of
the nine was
euthanized due to a fractured limb.
Statistical Analysis: None conducted.
Conclusions: Carfentanil citrate administered at 0.006 to 0.015 mg/kg produces immobilization in moose.
Adverse Reactions: None
Special Issues: None
3. Study Three in Moose.
Type of
Study: Field Study
Names and
Addresses of
Investigators:
T. Newman, J. D. Port, T.H. Stanley and
K. F. Willard
Department of
Anesthesiology
University of
Utah Medical Center
Salt Lake City, Utah
J. Kimball
Utah Division of
Wildlife Resources
Ogden, Utah
Study Design:
Purpose: The 3 moose reported in this study
were immobilized by aerial dart from
a capture gun in order to investigate injuries or
to relocate the animals.
Test Animals:
1) Number: 3
2) Age and
Sex: 1 cow, 1 calf and
1 adult bull
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Forms: Injectable liquid.
Route of
Administration: Intramuscular
Dosages Used: 0.005 - 0.012 mg/kg body weight
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results and
Conclusions:
The 3 moose (cow, calf and
adult bull) which
received 5.5 or
12 micrograms/kg were
immobilized within 6 to 22 minutes. Except for
a slightly elevated temperature (40.6° C) no other problems were
observed.
The animals were
removed or
released 1 hour following immobilization. One animal had to be destroyed due to physical injuries received prior to the immobilization.
Statistical Analysis: None conducted
Adverse Reactions: Elevated body temperature
Special Issues: None
4. Study Four in Moose.
Type of
Study: Field Study
Name and
Address of
Investigator:
Dr. William Taylor
Alaska Department of
Game & Fish
Anchorage, Alaska
Study Design:
Purpose: Determine efficacy of
Carfentanil in moose under
field conditions.
Test Animals:
1) Species: Moose (Alces alces)
2) Number: 38
3) Age and
Sex: Adults and
subadults of
both sexes.
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable Liquid
Route of
Administration: Intramuscular
Dosage Used: 0.008-0.020 mg/kg
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
In these 38 animals with an average weight of
467 kg Carfentanil administered at an average dose of
0.012 mg/kg body weight produced immobilization in an average of
4 minutes.
The immobilization was
effectively reversed with a narcotic antagonist.
Statistical analysis: None conducted
Conclusions:
The data gathered by Dr. Taylor in Alaska support the label dose range for
Carfentanil in moose of
0.005 - 0.020 mg/kg body weight.
Adverse Reactions: None
Special Issues: None
5. Study Five in Moose.
Type of
Study: Field Study
Name and
Address of
Investigator:
Mr. William Dalton
Department of
Natural Resources
Fort Francis, Ontario, Canada
Study Design:
Purpose: Demonstrate efficacy of
Carfentanil in moose.
Test Animals:
1) Moose (Alces alces)
2) Number: 16
3) Age and
Sex: Adults and
subadults of
both sexes
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular
Dosage Used: 0.0067 mg/kg body weight
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
Thirteen (13) of
the 16 animals had acceptable induction times.
Three (3) animals showed excessive induction times.
These were
interpreted by the investigator as being due to improper injection of
Carfentanil because of
the type of
dart used. All immobilized animals were
successfully reversed within an average time of
4.5 minutes with the use of
a narcotic antagonist.
Statistical Analysis: None conducted
Conclusions:
The data gathered by Mr. Dalton in Canada, support the recommended label dose range of
Carfentanil in moose of
0.005 - 0.020 mg/kg body weight.
Adverse Reactions: None
Special Issues: None
B. Studies Conducted in Elk
1. Trial One in Elk.
Type of
Study: Dose Determination
Names and
Addresses of
Investigators:
Thomas Meuleman, J.D. Port, T.H. Stanley and
K.F. Williard
Department of
Anesthesiology
University of
Utah Medical Center
Salt Lake City, Utah 84132
John Kimball
Utah Division of
Wildlife Resources
Ogden, Utah 84403
Study Design:
Purpose: Determine appropriate effective dose of
Carfentanil in elk with antagonism by diprenorphine.
Test Animals:
1) Species: Cervus elaphus
2) Number: 58
3) Age and
Sex: Adults of
both sexes
4) Semi-confined facilities
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular
Dosages Used:
1.25 to 12 micrograms per kilogram body weight (0.00125 - 0.012 mg/kg body weight). Six milligrams of
diprenorphine were
used as an antagonist in each animal.
Test Duration: 72 hours
Parameters Measured:
1) Dose Administration
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
(Eds. note: The following table consists of
two columns.)
Results of
Meuleman Trials: Dose Induction ---Micrograms/kg--- ---Time--- 1.25 (l0)* (a) 4.3 minutes 2.00 (14) (a) 3.5 minutes 5.00 (7) (a) 3.8 minutes 10.00 (6) (a) 1.8 minutes 4.4 to 6.6 (6) (b) 3.9 minutes 7.4 to 12.0 (7) (b) 1.8 minutes 7.9 (8) (c) 7.8 minutes *Numbers in ( ) indicate the number of
elk administered each dose. (a) These animals were
dosed by means of
a hand-held syringe. (b) These animals were
dosed by means of
a jab stick. (c) These animals were
administered the drug by a dart syringe. Statistical Analysis: None conducted.
Conclusion:
The data show a dose-related response and
indicate that 0.010 mg/kg delivered by hand-held syringe produces immobilization rapidly in this species. Data in eight animals indicate the need for
higher doses in animals injected by aerial dart syringes. Six milligrams of
diprenorphine effectively antagonized the immobilization effects of
this dose range of
Carfentanil.
Adverse Reactions: None Observed
Special Issues: None
2. Trial Two in Elk.
Type of
Study: Field
Names and
Addresses of
Investigators:
Dr. Peter L. Bailey, J.D. Post, J.L. Giese, P. Zwanikken, N.L. Pace, T. H. Stanley and
John Kimball
University of
Utah Medical Center
Salt Lake City, Utah 84132
Study Design:
Purpose: Evaluate appropriate safe and
effective dose of
Carfentanil in elk with antagonsim by diprenorphine.
Test Animals:
1) Number of
Animals: 18
2) Age and
Sex: Adult and
subadults of
both sexes.
3) Semi-confined conditions after capture.
Type of
Control:
Each animals served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular
Dosage Used:
0.00025 - 0.020 mg/kg body weight. Effects were
reversed with 5.2 to 10.0 mg diprenorphine.
Test Duration: 24 hours
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results of
Bailey, et al. Trials:
Dose in Induction Reversal Agent
Micrograms/Kg Time and
Recovery Time
0.25 (1)* Ataxia-never immobilized
0.30 (1) Ataxia-never immobilized
0.50 (4) Ataxia-never immobilized
0.60 (4) (1) 22 minutes Treatment with
M50-50 gave
recovery in 3-7
minutes.
0.75 (3) Mean time to immobilization Treatment with M50-
1.00 (2) was
16.2 minutes 50 gave recovery in
3-7 minutes.
6.00 (1) Mean time to immobilization Treatment with M50-
20.00 (1) was
1.6 minutes 50 was
successful.
20.00 (1)
* Figures in ( ) indicate the number of
elk administered each dose.
Statistical Analysis: None conducted
Conclusions:
Doses of
0.006 mg/kg or
higher produced satisfactory immobilization in elk. Doses of
0.001 mg/kg or
lower did not produce immobilization.
Adverse Reactions: One of
the three elk dosed at 0.0075 mg/kg was
found dead 2 days later.
Special Issues: None
3.
Third Study in Elk.
Type of
Study: Field Study
Name and
Address of
Investigator:
Dr. Albert W. Franzmann
Alaska Department of
Fish & Game
Soldotna, Alaska
Study Design:
Purpose:
Determine the effectiveness of
Carfentanil to immobilize free-ranging elk following helicopter pursuit.
Test Animals:
1) Number: 8
2) Age and
Sex: Adults females
3) Free-ranging
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular following helicopter pursuit.
Dosage Used: 0.015 mg/kg to 0.030 mg/kg
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
Carfentanil administered at an average dose of
0.020 mg/kg body weight (0.015 to 0.029 mg/kg range) produced an average time to immobilization of
4 minutes.
These immobilizations were
effectively antagonized by a narcotic antagonist.
Statistical Analysis: None conducted
Conclusions:
Free-ranging elk, pursued by helicopter, were
effectively immobilized with Carfentanil at an average dose rate of
0.020 mg/kg body weight.
Adverse Reactions: None
Special Issues: None
4. Fourth Study in Elk.
Type of
Study: Field Study
Name and
Address of
investigator:
Dr. Ted Kistner
Oregon Department of
Game & Fish
Corvallis, Oregon
Study Design:
Purpose: Demonstrate efficacy of
Carfentanil in free-ranging Roosevelt Elk following helicopter pursuit.
Test Animals:
1) Number 13
2) Age and
Sex: Adults of
both sexes
3) Free-ranging
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable
Route of
Administration: Intramuscular
Dosage Used: 0.010 - 0.026 mg/kg body weight
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
An average dose of
0.0159 mg/kg body weight produced immobilization in these elk in an average of
2.5 minutes. Reversal was
effectively accomplished with a narcotic antagonist.
Statistical Analysis: None conducted.
Conclusions:
This study
supports the recommended label dose range of
0.010 - 0.026 mg/kg body weight.
Adverse Reactions: None
Special Issues: None
5. Fifth Study in Elk.
Type of
Study: Field Study
Name and
Address of
Investigator:
Dr. Ted Kistner
Oregon Department of
Game & Fish
Corvallis, Oregon
Study Design:
Purpose: Demonstrate efficacy of
Carfentanil to immobilize free-ranging elk.
Test Animals:
1) Number: 70
2) Age and
Sex: Adults and
subadults of
both sexes.
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular
Dosage Used: 0.009 - 0.025 mg/kg body weight (0.015 mg/kg body weight, average)
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to Immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
This group of
animals was
effectively immobilized at an average of
0.015 mg/kg body weight with a dose range of
0.009 - 0.025 mg/kg. Average time to immobilization was
4.6 minutes in this group of
70 animals.
The immobilization effectively antagonized with a narcotic antagonist. Two mortalities occurred due to non-drug related injuries.
Statistical Analysis: None conducted.
Conclusions: This study
supports the recommended label dose range of
Carfentanil in elk.
Adverse Reactions: None
Special Issues: None
6. Sixth Study in Elk.
Type of
Study: Field Study
Name and
address of
Investigator:
Dr. Ted Kistner
Oregon Department of
Game & Fish
Corvallis, Oregon
Study Design:
Purpose:
Demonstrate efficacy of
Carfentanil in free-ranging elk following helicopter pursuit.
Test Animals:
1) Number: 60
2) Age and
Sex: Adult and
subadult females
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular
Dosage used: Average 0.011 mg/kg body weight
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
An average dose rate of
0.011 mg/kg body weight of
Carfentanil produced an average time-to-immobilization of
free-ranging elk of
5.13 minutes. All immobilized animals were
effectively reversed with a narcotic antagonist. One mortality occurred that was
not drug related.
Statistical Analysis: None conducted
Conclusions:
Free-ranging elk in this study
were effectively immobilized at an average dose rate of
0.011 mg/kg body weight and
reversed with a narcotic antagonist.
Adverse Reactions: None
Special Issues: None
7. Seventh Study in Elk.
Type of
Study: Field Study
Name and
Address of
Investigator:
Dr. Ted Kistner
Oregon Department of
Game & Fish
Corvallis, Oregon
Study Design:
Purpose: Determine the efficacy of
Carfentanil to immobilize free-ranging elk
Test Animals:
1) Number: 12
2) Age and
Sex: Adults and
subadults of
both sexes
Type of
Control:
Each animal served as its own control. No treatment type of
control was
deemed appropriate.
Diagnosis: N/A
Dose Form: Injectable liquid
Route of
Administration: Intramuscular following helicopter pursuit.
Dosage used: 0.013 - 0.029 mg/kg body weight (0.017 mg/kg body weight average).
Test Duration: N/A
Parameters Measured:
1) Dose Administered
2) Time to immobilization
3) Amount of
Antagonist
4) Time to Recovery
5) Adverse Effects
Results:
Eight of
the twelve elk dosed at an average of
.017 mg/kg were
immobilized within an average time of
4.6 minutes.
The remaining elk were
immobilized within an average time of
16 minutes.
Statistical Analysis: None conducted
Conclusions:
The data gathered during this study
are consistent with the data from
previous studies on immobilization of
free-ranging elk with Carfentanil and
supports the recommended dose range.
Adverse Reactions: None
Special Issues:
The initial results in some of
the elk in this study
underscore the need for
adequate injection of
Carfentanil for
maximum efficacy of
the drug. Inadequate injection results in prolonged induction times as occurred in four of
these elk.
8. Eighth Study in Elk.
Type of
Study: Field Study
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