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U.S. Department of Health and Human Services

Animal & Veterinary

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ANADA Public Master File (PMF) 5118 PANACUR

I. GENERAL INFORMATION:

NADAPublic Master File (PMF) 5118
Sponsor:IR-4 project
 
Generic Name:fenbendazole
Trade Name:PANACUR
Marketing Status: 

 

II. INDICATIONS FOR USE

For the removal and control of Haemonchus contortus and Ostertagia circumcincta in goats.

 

III. DOSAGE FORM, ROUTE OF ADMINISTRATION AND RECOMMENDED DOSAGE

  1. Dosage Form: Suspension (10%)
  2. Route of Administration: Oral drench.
  3. Recommended Dosage: 5 mg/kg body weight.

 

IV. PREVIOUS APPROVALS

Fenbendazole suspension is currently approved for use in horses and cattle as specified in 21 CFR 520.905a.

 

V. EFFECTIVENESS

A summary of one pivotal clinical study demonstrating the effectiveness of febendazole (sic) (FBZ) suspension in goats is provided.

(1) Type of Study: Efficacy Study (Clinical Trial).

(2) Name and Address of Investigator:

Dr. Donald L. Ferguson
Dept. of Veterinary Science
Institute of Agriculture & Natural Resources
University of Nebraska, Lincoln, NE 68583

(3) General Design of the Experiment

  1. Purpose of the Study: To determine the effectiveness of FBZ 10% suspension for the removal and control of gastrointestinal nematodes in goats.
  2. Test Animals: Twenty goats of both sexes (buck and does) were selected for this study. The goats ranged in age from approximately 3 to 8 months and were of commercial breed (Alpine, Nubian, Sannan or Toggenburg) or crossbreed. The animals were purchased from local producers and housed in the Large Animal Research Facility located on the East Campus of the University of Nebraska, Lincoln, Nebraska. The animals were acclimated 7 to 10 days prior to the beginning of the study.
  3. Feed: A commercial cattle feed was provided twice daily. Feed intake was not monitored. The analysis of the feed showed less than 12% crude protein, not less than 1% crude fat and 18% crude fiber. The feed was devoid of contaminants capable of interfering with the results of the study. Water was provided ad libitum with an automatic water device.
  4. Identification: Ear tag and pen number.
  5. Weight: Goats were weighed on Day 1 (day before treatment) and the weights ranged from 18 to 50 kg.
  6. Location: The study was conducted at the Large Animal Research Facility, Department of Veterinary Science located in the East Campus of the University of Nebraska, Lincoln, Nebraska.
  7. Treatment: The treatments were (i) naturally infected unmedicated control and (ii) naturally infected medicated group treated with 5 mg FBZ 10% suspension/kg body weight as a single drench.
  8. Test Duration: Goats were acclimated 7 to 10 days prior to initiating the study. The study began on May 2, 1987 and was completed on May 25, 1987.
  9. Diagnosis: The gastrointestinal parasitic infection in naturally infected goats was determined by daily microscopic examination of fecal samples collected from individual animal during the acclimation as well as the treatment periods for parasite egg counts. Anthelmintic efficacy of FBZ was finally assessed by comparing the postmortem worm counts in treated and untreated goats 9 to 12 days post-treatment.
  10. Dosage Form: Suspension
  11. Route of Administration: Oral
  12. Dosage Used: 5 mg FBZ/kg body weight single administration.
  13. Parameters:
    • Daily Observation
    • Mortality
    • Microscopic fecal examination of parasite eggs
    • Necropsy Findings

(4) Results: All the goats were naturally infected with gastrointestinal nematodes as evidenced by the presence of large numbers of eggs in the fecal samples when examined microscopically. Final assessment of the anthelmintic efficacy of FBZ was done by comparing post-mortem worm counts in treated and untreated goats. In this trial, the efficacy of FBZ (5 mg/kg dose) ranged from 73.3% to 85.5% against Haemonchus contortus and Ostertagia circumcincta, as shown below.

Nematodes Recovered at Necropsy

GroupGoat No.H.contortusO.circumcincta
Untreated09023,871110
090611,564232
09161,1810
09211423
092430
09531821
09542580
09631,03531
09671,303105
09784,71149

 

Total24,122551
Mean2412.255.1

 

GroupGoat No.H.contortusO.circumcincta
Treated09041,67526
09072,4840
09085915
09121440
091814511
0919420
092083
092520
0957560
099381435

 

Total596180
Mean596.18.0
Efficacy73.3%85.5

 

(5) Conclusions: The results of a clinical study in goats naturally infected with gastrointestinal nematodes demonstrated that a single oral treatment as a drench with FBZ 10% suspension at 5 mg/kg dose was efficacious in the removal and control of gastrointestinal parasitic infection with Haemonchus contortus and Ostertagia circumcincta.

 

VI. ANIMAL SAFETY

A summary of one pivotal study demonstrating the safety of FBZ 10% suspension in goats is provided.

(1) Type of Study: Target Animal Safety.

(2) Name and Address of Investigator:

Dr. Donald L. Ferguson
Dept. of Veterinary Science
Inst. of Agriculture & Natural Resources
University of Nebraska Lincoln, NE 68583

(3) General Design of the Study

  1. Purpose of the Study: To determine the safety of FBZ 10% suspension when administered orally as a drench in goats.
  2. Test Animals: Thirty healthy goats of both sexes (buck and does) of commercial breed (Nubian, Sannan, Alpine or Toggenburg) or crossbreed were allocated for this study. The goats were randomly assigned by weight and sex to each dosage levels and to a nonmedicated control group.
  3. Identification: Goats were identified by ear tag and pen number.
  4. Feed: A commercial cattle ration was provided twice daily. Feed intake was not monitored. Feed was free of contaminants to interfere with the results of the study. Water was provided ad libitum.
  5. Dosage form: Suspension
  6. Route of Administration: Oral drench
  7. Test Duration: 45 days
  8. Treatments: There were 5 treatment groups of six animals each: (a) nonmedicated control, (b) 5 FBZ/kg (1X) treated group, (c) 15 mg FBZ/kg (3X) treated group, (d) 30 mg FBZ/kg (6X) treated group and (e) 125 mg FBZ/kg (25X) treated group.
  9. Frequency of Drug Administration: Each goat in groups (b), (c), and (d) received one oral dosage daily for 3 consecutive days and group (e) received only one single dose.
  10. Pertinent Parameters: Daily clinical observations Necropsy Morbidity Mortality

(4) Results: Following drenching with FBZ suspension, all goats were observed hourly for 4 hours and at about 9 to 15 hours interval during the 14 days for signs of adverse reaction. The total observation period continued for 35 days and then the goats were sacrificed. No adverse reactions to FBZ were observed in this trial. Diarrhea was observed in 4 goats (goat # 0992, 0976, 0982, and 0979), one from each treatment group. Coccidia oocysts were observed in the feces of these goats. Two goats died during the experimental period. However at postmortem examination, the cause of death was diagnosed as pregnancy toxemia (ketosis) in goat #0981 from 5 mg/kg group and a chronic disease characterized by diffuse serous atrophy of fat, thymic atrophy and lymphoid depletion of the Peyer's patches in goat #0976 from the 15 mg/kg group. At the completion of the study, all the goats were sacrificed and posted. No gross pathology associated with the use of FBZ was observed in any of the animals at the postmortem examination.

(5) Conclusions: The data demonstrated that goats treated with 5 mg fenbendazole 10% suspension/kg body weight for 3 consecutive days showed no signs of toxicity associated with the administration of the drug product. Therefore, 5 mg fenbendazole/kg body weight dosage is safe to goats.

 

VII. HUMAN FOOD SAFETY

(1) Residue Studies to Establish a Withdrawal Period

The in-life portion of the tissue residue depletion study was conducted by:

Dr. Donald L. Ferguson
Dept. of Veterinary Science
Institute of Agriculture & Natural Resources
University of Nebraska, Lincoln, NE 68583

The analysis of the tissue samples was performed by:

Halina T. Kramar
Hazleton Laboratories America, Inc.
P. O. Box 7545
Madison, WI 53707

Twenty-four healthy goats of both sexes from 3 to 8 months of age were used in the study. Goats were from commercial breeds and weighed approximately 18 to 36 kg. The animals were fed a commercial cattle ration twice daily and water was available ad libitum. Twenty of the goats received a single oral dose of the fenbendazole suspension at the rate of 5 mg/kg body weight. The remaining four goats served as control animals.

The treated goats were sacrificed in groups of four at 1, 3, 5, 7 and 9 days postadministration. Liver and muscle samples were collected at necropsy and sent to the Pesticide Research Center, Michigan State University. Hazleton Laboratories America, Inc., Madison, WI received the liver and muscle samples from the Pesticide Research Center for analysis. Samples of fat, kidney and plasma were retained at the Department of Veterinary Science, University of Nebraska. The liver and muscle samples were analyzed using the determinative HPLC method developed to analyze for fenbendazole in cattle liver (NADA 128-620). The method was validated to 0.0201 ppm in goat liver and muscle tissue. The mean residue values (n = 4) with standard deviation for liver and muscle are shown in the next page.

Residues of Fenbendazole (ppm) in Goat Tissue Following Oral

Administration of 10% Suspension at 5 mg/kg

Time (days) after administration Liver Muscle 1 3.48 (+/-) 1.09 0.179 (+/-) 0.074 3 1.18 (+/-) 0.526 0.051 (+/-) 0.044 5 0.126 (+/-) 0.088 <0.0201 "</pre" 7 0.0201 9 CONTROLS below the limit of assay sensitivity are reported as> A statistical analysis using a 99% tolerance limit approach with 95% confidence was performed on the data from the residue study. The results of that analysis indicated that residues of parent fenbendazole decline to less than 0.8 ppm in liver by six days postdosing under the conditions of the study.

 

VIII. AGENCY CONCLUSIONS

The data submitted in this public master file (PMF) are supporting information for the effectiveness, target animal safety and human food safety data required by Section 512 of the Food, Drug, and Cosmetic Act with regard to the proposed use of fenbendazole for the removal and control of gastrointestinal nematodes in goats. FDA will consider this information along with other required data as support for NADAs that may be filed for this use of fenbendazole in goats.

The human food safety data indicate that goats treated with fenbendazole at the recommended dosage will require 6 days for the depletion of fenbendazole residue from the tissues.

FDA is publishing a notice of availability of this PMF to encourage sponsors to file new animal drug applications (NADAs) for fenbendazole for the use covered by the PMF. Sponsors will need to submit (1) data supporting extrapolation from a major species in which the drug is currently approved, or authorized reference to such data; and (2) the remaining data and information required for approval of an NADA.

Fenbendazole is currently approved for use as a 10% suspension in cattle; see 21 CFR 520.905a.