NADA 101-331 Dog Wormer Tablets - original approval

Approval Date: November 14, 1978

I. GENERAL INFORMATION:

II. INDICATIONS FOR USE

For the removal of large roundworms (ascarids), Toxocara canis and Toxascaris leonina and hookworms, Anyclostoma caninum and Uncinaria stenocephala in dogs. The presence of these parasites should be confirmed by laboratory fecal examination. Consult your veterinarian for assistance in the diagnosis, treatment and control of parasitism.

III. DOSAGE:

IV. EFFECTIVENESS:

A. Dosage Titration

It has been established in critical efficacy evaluations, control critical efficacy evaluations, and clinical nematode egg count studies that pyrantel pamoate at 2.27 mg pyrantel base/lb of body weight for dogs weighing more than 5 lbs body weight and 4.54 mg pyrantel base/ lb of body weight for dogs weighing less than 5 lbs body weight, administered orally to dogs, is safe and effective for the removal of large roundworms (ascarids) and hookworms as cited above.

The basic titration data supporting the dosage of 2.27 mg/lb (5 mg/kg) is contained by cross reference in Pfizer Inc's. approved NADA 100-237, Pyrantel Pamoate oral suspension. A letter of authorization dated May 20, 1975 from Pfizer is contained in NADA 101-331 for Ralston Purina to refer to NADA 100-237 for data supporting safety and efficacy of pyrantel pamoate.

Newer information gathered from specific studies with Pyrantel pamoate tablets indicated a somewhat higher dosage (4.54 mg/lb) is required in dogs weighing less than 5 pounds. Since no greater risk of toxicity would be present from this increased level, it was decided to provide in the labeling for the administration of one full 22.7 milligram tablet to dogs 10 pounds and under in order to insure satisfactory efficacy in the smaller animals.

B. Critical Laboratory Studies

In compliance with 21 CFR 514.111(a)(5)(vi) for controlled studies, the following adequate and well-controlled critical evaluations were conducted with the market product:

1. Trial:

R.P. Experiment #26 - University of Wisconsin

Investigator: A.C. Todd, Ph.D.

Institution

Department of Veterinary Science
University of Wisconsin
Madison, Wisconsin

Type of Investigation: Control Critical Efficacy Evaluation

Design of Investigation: Ten dogs infected with T. canis were
individually penned and treated with pyrantel pamoate oral tablets at the target dose level of 5 mg pyrantel base/kg of body weight.

Ten dogs were held as sham dosed controls.

All worms passed for 96 hours after treatment were recovered for identification and enumeration. The dogs were euthanized and the worms remaining in the intestinal tract recovered for identification and counted.

Criteria for pyrantel pamoate effectiveness was determined by comparing the number of worms eliminated in the feces versus the total number of worms eliminated in the feces plus those remaining in the gastrointestinal tract at necropsy.

Findings: An average percent reduction of 81% was obtained in the ten treated dogs. Four-tenths percent reduction in the worm burden of the 10 control dogs occurred at the same time.

2. Trial:

R.P. Experiment

Investigator: C.W. Dickerson, M.S.

Institution:

Ralston Purina Co. Research Farm
Type of Investigation: Control Critical Efficacy Evaluation.

Design of Investigation: Ten dogs infected with Uncinaria Stenocephala were individually penned and treated with pyrantel pamoate oral tablets at the target dose of 5 mg pyrantel base/kg of body weight (2.27 mg/lb).

Ten dogs were held as sham dosed controls.

All worms passed for 96 hours after treatment were recovered for identification and enumeration. The dogs were euthanized and the worms remaining in the intestinal tract recovered for identification and counted.

Criteria for pyrantel pamoate effectiveness was determined by comparing the number of worms eliminated in the feces versus the total number of worms eliminated in the feces plus those remaining in the gastrointestinal tract at necropsy.

Findings: An average percent reduction of 88.6% was obtained in the ten treated dogs. 0.5% reduction in the worm burden of the 10 control dogs was observed concurrently. When worm burdens from treated dogs was compared to worm burdens of control dogs at necropsy an efficacy of greater than 95% was calculated for the drug.

The following partially-controlled critical laboratory studies were conducted in addition to the above two well-controlled evaluations:

3. Trial:

R.P. Experiments # 1 through # 11

Investigator: C.W. Dickerson, M.S.

Institution:

Ralston Purina Co.
Research Farm
Gray Summit, MO

Type of Investigation: Critical Efficacy Evaluations

Design of Investigation: A total one-hundred and thirteen dogs infected with varying combinations of ascarids and hookworms were individually penned and treated with pyrantel pamoate oral tablets at the target dose level of 2.27 mg pyrantel base/lb of body weight. A total of sixteen dogs were retained as unmedicated controls.

All worms passed for 96 hours after treatment were recovered for identification and enumeration. The dogs were euthanized and the worms remaining in the intestinal tract recovered for identification and counted.

Criteria for pyrantel pamoate effectiveness was determined by comparing the number of worms eliminated in the feces versus the total number of worms eliminated in the feces plus those remaining in the gastrointestinal tract at necropsy.

Findings: Pyrantel pamoate was highly efficacious at the target dose of 2.27 mg pyrantel base/lb against T. canis (95%), T. leonina (98%), A. caninum (96%), and U. stenocephala (92%7.

4. Trial:

R.P. Experiment #12 - Kansas State

Investigator: W.D. Lindquist, D.Sc.

Institution:

Department of Infectious Diseases
College of Veterinary Medicine
Kansas State University
Manhattan. Kansas

Type of Investigation: Critical Efficacy Evaluation

Design of Investigation: Eleven dogs infected with varying combinations of ascarids and hookworms were individually penned and treated with pyrantel pamoate oral tablets at the target dose level of 2.27 mg pyrantel base/lb or body weight.

All worms passed for 72 hours after treatment were recovered for identification and enumeration. The dogs were euthanized and the worms remaining in the intestinal tract recovered for identification and counted.

Criteria for pyrantel pamoate effectiveness was determined by comparing the number of worms eliminated in the feces versus the total number of worms eliminated in the feces plus those remaining in the gastrointestinal tract at necropsy.

Findings: Pyrantel pamoate was highly efficacious at the target dose of 2.27 mg pyrantel base/lb against T. canis (90%), T. leonina (92%), and A. caninure (99%).

Clinical (Field) Studies

1. Trial:

R.P. Experiment #18

Investigator: William M. Stone, M.S.

Institution:

Veterinary Diagnostic and Investigational Laboratory
School of Veterinary Medicine
University of Georgia
Tifton, Georgia

Type of Investigation: Clinical nematode egg count

Design of Study: Thirteen racing Greyhounds were medicated with pyrantel pamoate oral tablets at the target dose level of 2.27 mg pyrantel base/lb or body weight. Fecal samples were obtained for nematode egg counts on day 4.

Criteria for pyrantel pamoate effectiveness was determined by monitoring nematode egg count data pre and post-medication.

Findings: Pyrantel pamoate was highly efficacious (97%) against hookworm infections.

2. Three (3) clinical trials were conducted with Purina Dog Wormer Tablets which included 33 treated dogs. No signs of toxicity or other related side effects were noted.

a. William A. Krumrey, D.V.M.
Yorkshire Animal Hospital
8088 Watson Road
St. Louis, Missouri 63119

Treated twelve (12) dogs between August 21, 1974, to October 1, 1974. All were totally cleared of Ascarids and/or hookworm eggs following treatment.

b. John C. Eckert, D.V.M.
Concord Animal Hospital
11705 Concord Village Avenue
St. Louis, Missouri 63128

Treated twelve (12) dogs between August 29, 1974, to October 28, 1974. Five (5) of seven (7) dogs treated were totally cleared of Ascarids and for hookworms eggs following treatment. Five (5) dogs were either not infected or no post treatment fecal sample was obtained.

c. Suzanne Saueressig, D.V.M.
Humane Society of Missouri
1210 Macklind Avenue
St. Louis, Missouri 63110

Treated nine (9) dogs between August 26, 1974 and November 16, 1974 Of the two (2) dogs trested in which post-treatment examinations were made, one roundworm and two hookworm infections were controlled.

The field studies described above were open evaluations and not in direct compliance with 21 CFR 514.111(a)(5)(vi) for controlled comparisons. Accordingly, the requirement for controlled field evaluations was waived by the agency. The basis for waiver is that the results of the critical laboratory trials are considered to be adequate to establish the effectiveness of the product.
At the time of conduct of these trials, several years ago, controlled field studies were not a recommended or required procedure.

As a result, in addition to the limited trials outlined above, several hundred other animals were dosed with either pyrantel pamoate tablets or suspension in individual field evaluations. These studies were primarily designed to assess the clinical safety of the formulations and not so much the actual efficacy of the drug. As stated previously, critical anthelmintic measurements provide more substantial and objective evidence on the effectiveness of a compound, than do non-critical observations.

D. Supportive Data:

In addition to the above studies, critical efficacy evaluations were conducted with a susupension formulation of pyrantel pamoate, covered by NADA 100-237. A total of 5 additional studies involving 90 critical efficacy observations with the suspension were submitted to support the effectivemess of the tablet formulation of pyrantel pamoate for dogs. The results of these related efficacy studies with the suspension formulation are summarized in Table 1 and compared to the efficacy results obtained for the tablets which were reported induvidually above. Foreign critical and clinical trials are contained in the cross-referenced NADA 100-237 as supportive information.

The names and addresses of investigators conducting the related safety and efficacy studies are presented Table 2.

V. ANIMAL SAFETY:

Animal safety of pyrantel pamoate oral dosage forms has been adequately demonstrated per Pfizer, Inc. approved NADA 100-237. Pfizer, Inc. provided authorization to Ralston Purina Company on May 20, 1975 to refer to safety data contained in Pfizer, Inc. NADA's 091-739, 100-237 and 016-883 in support of NADA 101-331 on page 00035.

VI. HUMAN SAFETY:

Pyrantel pamoate oral tablets are indicated for use only in non-food producing animals. The risk of toxicity from accidental human exposure is considered low since it is intended for limited dosing. The drug is approved for use in humans and is considered to have a wide margin of safety.

VII. AGENCY CONCLUSIONS:

The data submitted in support of this NADA complies with the requirements of 512 of the Act and demonstrate that Purina Dog Wormer Tablets when used under its proposed conditions of use is safe and effective for the treatment of roundworm and hookworm infection in dogs.

(Eds. Note: The following table consists of 6 columns.)

TABLE 1 Worm Count Summary

COMPARATIVE EFFICACY OF PYRANTEL PAMOATE ORAL DOSAGE FORMULATIONS*

*Dosage rate of 2.27 mg. base/lb. of body weight.
**Worms passed after treatment (96 hr.) and recovered in the intestinal tract at necropsy.

(Eds. Note: The following table consists of 7 columns.)

TABLE 2

Names and Locations of Investigators Who Participated in Related Efficacy (Suspension Formulation) and Safety Evaluation Programs

VIII. LABELING (Attached)

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Copies of applicable labels 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.