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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 140-892 Synanthic® Bovine Dewormer Paste, 18.5% - original approval

Approval Date: June 29, 1993

I. GENERAL INFORMATION:

NADA140-892
Sponsor:Syntex Animal Health
Division of Syntex Agribusiness, Inc.
3401 Hillview Avenue
Palo Alto, CA 94304
Generic Name:oxfendazole
Trade Name:Synanthic® Bovine Dewormer Paste, 18.5%
Marketing Status: 

 

II. INDICATIONS FOR USE

Oxfendazole is indicated for use in cattle (excluding female dairy cattle of breeding age) for the removal and control of:

  • Lungworms (Dictyocaulus viviparus): Adult, L-4.
  • Stomach  worms:
    • Barberpole worms (Haemonchus contortus and H. placei): Adult.
    • Brown stomach worms (Ostertagia ostertagi): Adult, L-4, and inhibited L-4 larvae.
    • Small  stomach  worms(Trichostrongylus axei): Adult.
  • Intestinal  worms:
    • Hookworms (Bunostomum phlebotomum): Adult.
    • Small intestinal worm (Cooperia punctata, C. oncophora and C. mcmasteri): 
    • Adult, L-4. Tapeworms (Moniezia benedeni): Adult.
    • Nodular worms (Oesophagostomum radiatum): Adult.

 

III. DOSAGE

A.DOSAGE FORM18.5% oxfendazole paste
B.ROUTE OF ADMINISTRATIONoral administration
C.RECOMMENDED DOSAGES:4.5 mg oxfendazole/kg body weight (2.05 mg/lb).

 

IV. EFFECTIVENESS

The effectiveness of oxfendazole suspensions (9.06% and 22.5%) was extensively evaluated in cattle and adequately described in the FOI summary of the approved NADA 140-854 (copy attached). In addition, two dose confirmation- comparison trials were evaluated. These trials were conducted to demonstrate that the approved suspension formulations and the paste formulation had similar biological effectiveness (bioavailability end points) in removing the parasites listed on the labels of the approved formulations. The approved suspension formulations and the paste formulation were administered at the same dosage levels (4.5 mg/kg) and compared to support approval of the paste formulation. The efficacy was calculated as follows:

N in control animal - N in treated animals / N in control animals X 100 = % Removal

N = Number of parasites

Trial No. IAS-1134-761 (VC-464). Dose Confirmation-Comparison Trial. R. Bradley. University of Florida, Gainesville, Florida. A total of 47 cattle with natural infections of gastrointestinal parasites was divided into five groups. Group 1 (15 animals) served as unmedicated controls, and groups 2, 3, 4 and 5 (8 animals per group) were administered a single dose of either one of the three approved suspension formulations or the paste formulation of oxfendazole at a dosage level of 4.5 mg/kg. The following results were reported for adult stages of the parasites:

(Eds. Note: The following table consists of 5 columns.)

Formulation18.5 PA22.5 PO9.06 PO22.5 IR
Parasite% Efficacy% Efficacy% Efficacy% Efficacy
H. placei100.0100.0100.0100.0
O. ostertagi100.0100.0100.0100.0
C. pectinata100.099.9100.099.9
C. punctata100.099.9100.099.9
Oes. radiatum100.0100.0100.0100.0

PA=Paste;
PO=Suspension, oral (approved);
IR= Suspension, intraruminally (approved)

These results indicate that the paste formulation provides identical biological results against the parasites as two approved formulations. Trial No. IAS-1134-775 (VC-457). Dose Confirmation-Comparison Trial. T. Yazwinski. University of Arkansas, Fayetteville, Arkansas. A total of 46 cattle with natural infections of gastrointestinal parasites were divided into five groups. Group 1 (15 animals) served as unmedicated controls, group 2 (7 animals), groups 3, 4, and 5 (each had 8 animals per group) were treatment groups using different dosage forms. The four treated groups received a single administration of suspension or paste formulations of oxfendazole at a dosage level of 4.5 mg/kg. The following results were reported for the four treated groups concerning adult stages of parasites:

(Eds. Note: The following table consists of 5 columns.)

Formulation18.5 PA22.5 PO9.06 PO22.5 IR
Parasite% Efficacy% Efficacy% Efficacy% Efficacy
H. placei 100.0100.0100.097.6
O. ostertagi99.9 99.8 100.0100.0
Trich. axei 99.7 100.0100.0100.0
C.mcmasteri99.9100.099.999.9
C.oncophora99.9100.099.999.9
C.punctata 100.0100.099.999.9
B.phlebotomum100.0100.097.7100.0
Oes. radiatum100.0100.098.997.7

PA=Paste;
PO=Suspension, oral (approved);
IR= Suspension, intraruminally (approved)

The results indicate that the paste formulation provides identical biological results against the parasites as the two approved formulations. Conclusion

The results from the two confirmation-comparison trials indicate that the oral paste formulation has the same biological anthelmintic effectiveness against the major gastrointestinal parasites as the oral suspension and the intraruminal injection dosage forms. Therefore, it is concluded on the basis of clinical veterinary medical judgment that the results of the two studies support the same claims of efficacy for the paste formulation as that of the oral suspension and intraruminal injection formulations provided in NADA 140- 854.

 

V. TARGET ANIMAL SAFETY

The safety of oxfendazole was extensively evaluated in cattle and the results described in the FOI summary of the approved NADA 140-854 are applicable to this application.

 

VI. HUMAN FOOD SAFETY:

The human food safety aspects of oxfendazole were extensively evaluated and described in the FOI summary, Sections 6.A. to 6.F. and 6.H., of approved NADA 140-854. However, the 7-day withdrawal time mentioned in Section 6.E. of the FOI summary of NADA 140-854 was specific for the suspension dosage form of oxfendazole, and a separate withdrawal study (IAS 1134-953) was conducted in order to determine a withdrawal time for the 18.5% oxfendazole paste formulation.

Withdrawal Time (Study IAS 1134-953)

The study involved 20 treated beef-breed calves (10 steers and 10 heifers) which were dosed orally with the paste. The target dose was 4.5 mg of oxfendazole per kg of body weight. The calves were arranged in groups of four (two of each sex) and were killed at 4, 5, 6, 7 or 8 days postdosing.

The liver of each animal was collected at the time of slaughter and the concentration of the marker substance fenbendazole was determined by HPLC method developed by Syntex (BMS Method 87005.2). The average results of those assays are shown below.

Days Post DosingLevels (ppm) of the marker substance, fenbendazole in liver tissue
41.270 (+/-1.452)
51.919 (+/- 3.157)
60.161 (+/- 0.128)
70.147 (+/- 0.157)
80.041 (+/- 0.037)

A problem during the dosing of the animals caused three of the calves to receive less than the intended dose. As a result, the liver values from those animals were not used in the calculation of the withdrawal time. The remaining 17 liver residue values were analyzed statistically to determine tolerance limits (upper 99th percentile of the population determined with 95% confidence) for the concentration of the fenbendazole in the liver. The analysis of the data with the Rm of 0.8 ppm for the fenbendazole marker gave a withdrawal time of 11 days for cattle treated with the paste formulation of oxfendazole.

 

VII. AGENCY CONCLUSIONS

The data submitted in support of this NADA satisfy the requirements of Section 512 of the Federal Food, Drug, and Cosmetic Act and with 21 CFR 514 of the implementing regulations. The data demonstrate that oxfendazole "SYNANTHIC ® Bovine Dewormer" paste, 18.5%, when used under the labeled conditions of use in cattle is safe and effective for the removal and control of lung and gastrointestinal worms. This approval also relies on the approved NADA 140-854 (oxfendazole 9.06% and 22.5% suspensions) and makes direct reference to the specific sections involved.

A tolerance is established for total oxfendazole residues in edible cattle tissues based on a marker residue concentration of 0.8 ppm fenbendazole in the target tissue liver. A fenbendazole concentration of 0.8 ppm in liver corresponds to a total safe concentration of oxfendazole residues of 0.84 ppm in muscle, 1.7 ppm in liver, 2.5 ppm in kidney, and 3.3 ppm in fat. Oxfendazole and fenbendazole are benzimidazole anthelmintics with an identical metabolite pattern. Fenbendazole is a major metabolite of both drugs.

A withdrawal period of 11 days has been established for 18.5% oxfendazole paste at 4.5 mg/kg (2.05 mg/lb) dosage based on a statistical analysis of the depletion data, using an upper tolerance limit containing 99 percent of the population with a 95% confidence limit.

Because of the drug's route of administration, conditions to be treated, and the ability of a layperson to determine these conditions, the agency has concluded that 18.5% oxfendazole paste labeling contains adequate directions for use by a layperson and thus, the drug may be marketed over-the-counter. The oral suspensions of oxfendazole have an approved product available as an OTC product at 4.5 mg/kg dosage (21 CFR 520.1630).

The agency has carefully considered the potential environmental effects of this action and has concluded that the action will not have a significant impact on the human environment and that neither an environmental assessment nor an environmental impact statement is required.

Under section 512(c)(2)(F)(ii) of the Federal Food, Drug, and Cosmetic Act, this approval for food producing animals qualifies for 3 years of marketing exclusivity beginning on the date of approval because new clinical or field investigations (other than bioequivalence or residue studies) were essential to the approval of the application and conducted or sponsored by the applicant.

 

VIII. LABELING (Attached)

  1. (Synanthic ® Paste, 18.5%

Copies of these labels may be obtained by writing to the:

Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855