Pyrantel Pamoate: what the FDA reviewed for dog products

Primex® 2-X Primex® Canine NADA 200-352, Original approval, August 20, 2003; sponsor First Priority, Inc.; species: Dogs and puppies; foi_id 1106; FDA PDF

Indication

Removal of large roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies; prevention of T. canis reinfestation in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

1 full teaspoon (5 mL) per 10 lb body weight (Canine-2X) or per 5 lb body weight (Canine), oral (suspension), single labeled dose (as pioneer Nemex-2 / RFD), PRIMEX Canine-2X contains 4.54 mg and PRIMEX Canine 2.27 mg pyrantel base per mL

Recommended Dosage: PRIMEX Canine-2X: Administer 1 full teaspoon (5 mL) for each 10 lb of body weight. PRIMEX Canine: Administer 1 full teaspoon (5 mL) for each 5 lb of body weight.

Effectiveness

Biowaiver: no in vivo bioequivalence study; same active ingredient, concentration and dosage form as pioneer NEMEX-2 / RFD (NADA 100-237), no inactive ingredients affecting absorption; result: Waiver granted July 3, 2001

Based on the formulation characteristics of the generic product, First Priority, Inc. was granted a waiver on July 3, 2001, from the requirement for an in vivo bioequivalence study for the generic products PRIMEX Canine-2X and PRIMEX Canine (pyrantel pamoate).

Extraction notes: Generic ANADA with biowaiver; no studies. Effectiveness entry records the waiver only.

WormX® NADA 200-600, Original approval, February 03, 2016; sponsor Sergeant’s Pet Care Products Inc.; species: Dogs; foi_id 1265; FDA PDF

Indication

Removal of hookworms (Ancylostoma caninum, Uncinaria stenocephala) and large roundworms (Toxocara canis, Toxascaris leonina) in puppies and dogs; prevention of reinfection of large roundworms (T. canis) in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

1 tablet per 10 lb body weight, designed to provide at least 2.27 mg per pound for dogs over 5 lb and at least 4.54 mg per pound for dogs 5 lb or less, oral (flavored tablet), single treatment, 22.7 mg tablet for puppies/small dogs (half tablet per additional 5 lb over 10 lb); 113.5 mg tablet for dogs over 25 lb (half tablet at 25 lb up to 2 tablets at 76-100 lb); bioequivalence studies dosed 5 mg/kg

For the removal of large roundworms (Ascarids) and hookworms, give 1 tablet for each 10 lb of body weight. Dosage is designed to provide at least 2.27 mg per pound body weight for dogs weighing over 5 lb, and at least 4.54 mg per pound of body weight for dogs weighing 5 lb or less.

Effectiveness

Two masked, controlled clinical end-point bioequivalence studies vs RLNAD D-WORM in juvenile male dogs with induced Toxocara canis infection (22.7 mg study: 24 Beagles, 8 per group; 113.5 mg study: 30 mongrels, 10 per group); primary variable worm count at necropsy Day 10; n = Twenty-four (8 dogs per group); primary endpoint: recovered worm count at necropsy on Study Day 10 (Wilcoxon rank sum vs control; >90% effectiveness); result: 22.7 mg: generic 90.7% vs D-Worm 91.1% effectiveness (p=0.0057 and 0.0052 vs control); 113.5 mg: generic 99.6% vs D-Worm 93.3% (p=0.0009 and 0.0024); both strengths concluded bioequivalent

Twenty-four infected animals, ranked by fecal egg counts, were randomly allocated to test, reference, and control groups (8 dogs per group).

Adverse reactions

Extraction notes: Generic ANADA. CVM did not require effectiveness or target animal safety studies (target_animal_safety null); the effectiveness entry is the clinical end-point bioequivalence study. The summary refers to 'comparative bioavailability' but reports no plasma PK values. Adverse event counts not tabulated, so treated/control null.

Pyrantel Pamoate Chewable Tablets NADA 200-281, Original approval, January 03, 2001; sponsor Virbac AH, Inc.; species: Canine; foi_id 1035; FDA PDF

Indication

Removal of large roundworms (ascarids; Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies; prevention of T. canis reinfection in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

minimum 2.27 mg pyrantel base/lb (5 mg/kg) for dogs over 5 lbs; minimum 4.54 mg pyrantel base/lb (10 mg/kg) for dogs 5 lbs or less, oral (flavored chewable tablet), single treatment, 22.7 mg tablet: one per 10 lb (half tablet per additional 5 lb); 113.5 mg tablet: half tablet at 25 lb, 1 at 26-50 lb, 1.5 at 51-75 lb, 2 at 76-100 lb

Labeled Dosage: A minimum of 2.27 mg pyrantel base/lb. of body weight (5mg/kg) for dogs weighing over 5 lbs. and a minimum of 4.54 mg pyrantel base/lb. of body weight (10mg/kg) for dogs weighing 5 lbs. or less.

Effectiveness

Clinical end-point bioequivalence study vs pioneer D-Worm in Beagles with induced Toxocara canis infection (300 embryonated eggs; 42 inoculated, 36 randomized to generic, pioneer or untreated control, 6 males and 6 females per group), single dose at 49 days post-inoculation, masked, necropsy at 56 days; n = 36; primary endpoint: percent efficacy from mean (log-transformed) T. canis worm counts at necropsy; result: Generic 84.93% vs pioneer 81.35% efficacy (back-transformed mean worm counts 2.75 vs 3.42; controls 18.32; p<0.0001 vs control); 90% CI within +/-10% of pioneer improvement, bioequivalence established. Palatability study in 68 client-owned dogs: 89.7% vs 92.6% ate tablet within 3 minutes (p=0.4795)

The 36 dogs (18 males, 18 females) with the highest mean egg per gram counts (EPGs) were stratified by EPGs within gender, and randomly assigned to one of three treatment groups (6 males and 6 females per group).

Extraction notes: Generic ANADA; target animal safety relies on pioneer NADA 139-191 / 101-331 (target_animal_safety null). A second natural-infection bioequivalence study was inadequate (insufficient parasite burden) and drew no conclusions. No adverse reactions reported in the summary.

Pyrantel Pamoate Suspension Pyrantel Pamoate Suspension-2.27mg Pyrantel Pamoate Suspension-4.54mg NADA 200-248, Original approval, July 16, 1998; sponsor Cronus Pharma Specialities India Private Ltd.; species: Puppies and Dogs (ONLY); foi_id 1917; FDA PDF

Indication

Prevention of Toxocara canis reinfection in puppies, adult dogs and lactating bitches after whelping; removal of large roundworms (T. canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies.

Dose regimen

one full teaspoonful (5mL) per 10 lb body weight (4.54 mg/mL suspension), oral (suspension; food need not be withheld), single dose; puppies at 2, 3, 4, 6, 8 and 10 weeks; lactating bitches 2-3 weeks after whelping; adult dogs in contaminated quarters monthly, 2.27 mg/mL suspension: one full teaspoonful (5 mL) per 5 lb body weight; follow-up fecal exam 2-4 weeks after first treatment under constant exposure

Labeled Dosage: 4.54 mg/mL For the removal of large roundworms (ascarids) and hookworms. Administer one full teaspoonful (5mL) for each 10 lb of body weight.

Effectiveness

Biowaiver: no in vivo bioequivalence study required; generic contains the same active and inactive ingredients in the same concentration as the pioneer; result: Waiver granted

Based on the formulation characteristics of the generic product, Phoenix Scientific Inc. was granted a waiver from the requirement of an in vivo bioequivalence study for the generic product Pyrantel Pamoate Oral Suspension.

Extraction notes: Generic ANADA with biowaiver; no safety or effectiveness studies. Effectiveness entry records the waiver only.

Evict® NADA 200-028, Supplemental approval, June 04, 1997; sponsor Pegasus Laboratories, Inc.; species: Canine (puppies and dogs); foi_id 1663; FDA PDF

Indication

Prevention of Toxocara canis reinfection in puppies, adult dogs and lactating bitches after whelping; removal of large roundworms and hookworms in dogs and puppies.

Dose regimen

4.54 mg pyrantel base per mL (double-strength suspension), oral, with or without food, not stated in this supplement summary (as pioneer Nemex-2)

Each mL contains 4.54 mg of pyrantel base as pyrantel pamoate.

Effectiveness

Biowaiver: no in vivo bioequivalence study; safety and effectiveness based on chemical equivalence to pioneer Nemex-2 (NADA 100-237); result: Waiver granted; generic and pioneer are suspensions with the same active and similar inactive ingredients

Based upon the formulation characteristics of the generic product, Lambert-Kay, Division of Carter-Wallace, Inc. was granted a waiver from conducting an in vivo bioequivalence study with pyrantel double strength.

Extraction notes: Supplemental ANADA providing a double-strength (4.54 mg/mL) suspension. No studies; effectiveness entry records the biowaiver only. Indication quote preserves the summary's misspelling 'Toxacara'. Labeled per-weight dose not given in this summary.

Evict® NADA 200-028, Original approval, March 28, 1996; sponsor Pegasus Laboratories, Inc.; species: Dogs; foi_id 961; FDA PDF

Indication

Removal of large roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies; prevention of T. canis reinfection in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

1 teaspoonful (5 mL) per 5 pounds body weight, oral (suspension), single labeled dose (as pioneer Nemex), each mL contains 2.27 mg pyrantel base; studies dosed 1 mL/lb, equivalent to 2.27 mg pyrantel base/lb

Labeled Dosage: 1 teaspoonful (5 mL) for each 5 pounds of body weight

Effectiveness

Bioequivalence controlled anthelmintic test vs pioneer Nemex in ~6-week-old dogs artificially infected with T. canis and A. caninum (10 Lambert Kay, 10 Nemex, 9 untreated controls), single oral dose, necropsy 72 hours post-treatment; plus a 20-dog two-period crossover palatability test; n = 29; primary endpoint: percent efficacy from worm counts at necropsy; result: Lambert Kay pyrantel: 98% (T. canis) and 99% (A. caninum); Nemex: 100% and 100%; concluded bioequivalent. Palatability: no clinically significant difference (14 vs 15 of 20 dogs consumed directly)

A total of 29 dogs of both sexes, mixed breeding and approximately six weeks of age, were enrolled in the study.

Adverse reactions

Extraction notes: Generic (ANADA); target animal safety referenced to pioneer NADA 100-237 (target_animal_safety null). Adverse reaction count given in words ('one'), so treated left null. No adverse reactions in the palatability test.

Dog Wormer Tablets NADA 101-331, Supplemental approval, May 25, 1984; sponsor Farnam Companies, Inc.; species: Dogs (puppies, lactating bitches and adult dogs); foi_id 352; FDA PDF

Indication

Control of roundworms (ascarids), Toxocara canis, with repeat treatment in puppies, lactating bitches and adult dogs (supplement); removal of roundworms and hookworms per original approval.

Dose regimen

Minimum 2.27 mg pyrantel base per pound body weight (dogs over 5 pounds); 4.54 mg pyrantel base per pound for dogs 5 lbs or less, Oral (tablet in meat or placed in the back of the mouth), Puppies at 2, 3, 4, 6, 8 and 10 weeks of age; lactating bitches 2-3 weeks after whelping; adult dogs at monthly intervals, Tablets of 22.7, 45.4 and 113.5 mg pyrantel base (1 tablet per 10, 20 or 50 lbs respectively); OTC.

Label directions are designed to provide a minimum of 2.27 mg pyrantel base per pound body weight for dogs weighing more than 5 pounds body weight, and 4.54 mg pyrantel base per pound body weight for dogs weighing 5 lbs or less.

Effectiveness

Controlled critical study (Dickerson, Health Industries Research Center): 4 bitches inoculated with T. canis eggs before pregnancy produced 25 puppies allotted to multidose (label dosing at 2, 3, 4, 6, 8 and 10 weeks), single dose (2 weeks) and untreated control groups; necropsy worm counts at 11 weeks.; n = 25 puppies (9 multidose, 10 single dose, 6 control); primary endpoint: Average T. canis worms per pup at necropsy (percent reduction vs control); result: Multidose group: 0 worms (100% reduction, complete freedom from adult T. canis); single dose: 41.7 worms (25% reduction); control: 55.7 worms. Supporting open field study in 181 puppies from 29 litters: all negative for T. canis eggs at 4 weeks except 3 negative at 6 weeks.

Mix breed dogs, 4 bitchs, produced 25 puppies for three test groups. Multidose - 9 puppies Single Dose - 10 puppies Control - 6 puppies

Adverse reactions

Extraction notes: Category II supplemental approval (change in dosing schedule) based on literature and additional effectiveness studies; target animal safety refers to Pfizer NADAs 91-739, 100-237 and 16-803 by authorization and contains no study data. Species is not given in a General Information field; recorded from the indication wording.

Dog Wormer Tablets NADA 101-331, Original approval, November 14, 1978; sponsor Farnam Companies, Inc.; species: Dogs; foi_id 1824; FDA PDF

Indication

Removal of large roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs.

Dose regimen

2.27 mg pyrantel base/lb body weight (dogs more than 5 lbs); 4.54 mg pyrantel base/lb for dogs less than 5 lbs, Oral (tablet in meat or placed in the back of the mouth), Single treatment (not otherwise stated), Tablets of 22.7, 45.4 and 113.5 mg pyrantel base (1 tablet per 10, 20 or 50 lbs); 2.27 mg/lb corresponds to 5 mg/kg; one full 22.7 mg tablet for dogs 10 pounds and under.

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.

Effectiveness

Two well-controlled critical efficacy evaluations (Todd, University of Wisconsin, T. canis; Dickerson, Ralston Purina, U. stenocephala): ten infected dogs treated with tablets at 5 mg pyrantel base/kg vs ten sham-dosed controls, worms passed for 96 hours plus worms remaining at necropsy; supported by partially controlled critical studies (113 dogs, Experiments 1-11; 11 dogs, Kansas State) and clinical egg-count trials.; n = Ten treated and ten sham-dosed controls (Todd trial); primary endpoint: Percent reduction in worm burden (worms eliminated in feces vs total eliminated plus remaining at necropsy); result: T. canis: 81% average reduction in treated dogs vs 0.4% in controls; U. stenocephala: 88.6% reduction (>95% efficacy vs control necropsy burdens); Experiments 1-11: T. canis 95%, T. leonina 98%, A. caninum 96%, U. stenocephala 92%; Kansas State: T. canis 90%, T. leonina 92%, A. caninum 99%.

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.

Adverse reactions

Extraction notes: Original NADA 1978. Target animal safety refers by authorization to Pfizer NADAs 091-739, 100-237 and 016-883 (no study data in this summary). Controlled field studies were waived; Table 1 (worm count summary, 2.27 mg base/lb) gives tablet efficacy of 83% (T. canis), 98% (T. leonina), 96% (A. caninum) and 89% (U. stenocephala). Species stated only in the indication ('in dogs').

Adams™ D-Worm™ Dog Wormer Chewable Tablets NADA 139-191, Original approval, October 13, 1987; sponsor Farnam Companies, Inc.; species: Dogs and puppies; foi_id 450; FDA PDF

Indication

Removal of ascarids (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies; prevention of T. canis reinfection in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

minimum 2.27 mg pyrantel base per pound body weight for dogs over 5 pounds; 4.54 mg pyrantel base per pound for dogs 5 lbs or less, oral (chewable tablet, hand-offered or in food container, with or without food), single treatment; puppies at 2, 3, 4, 6, 8 and 10 weeks of age; lactating bitches 2-3 weeks after whelping; adult dogs at monthly intervals, 22.7 mg tablet: 1 tablet per 10 lb (1 tablet for dogs under 5 lb); 113.5 mg tablet: 1 tablet per 50 lb (may be halved for 25 lb)

Label directions are designed to provide a minimum of 2.27 mg pyrantel base per pound body weight for dogs weighing more than 5 pounds body weight, and 4.54 mg pyrantel base per pound body weight for dogs weighing 5 lbs. or less.

Pharmacokinetics

Effectiveness

Acceptance (palatability) test of chewable tablets hand-offered to penned dogs with 15 minutes to consume; therapeutic equivalence to the approved regular tablet (NADA 101-331) established by physical/chemical data rather than a new efficacy trial; n = 89; primary endpoint: full consumption of allotted dose within 15 minutes; result: 86/89 dogs (97%) fully consumed the dose within 15 minutes; a separate home-environment test in 40 dogs found 94% consumed the tablet within 15 minutes

Eighty-six out of 89 dogs (97%) fully consumed the alloted dosage within the 15 minute time period.

Extraction notes: 1987 original approval for a chewable reformulation. No anthelmintic efficacy trial or target animal safety study in this summary: effectiveness relies on NADA 101-331 and safety on Pfizer NADA 100-237 (and 91-739, 16-803) by authorization letter; target_animal_safety therefore null. Only palatability/acceptance tests are reported; no adverse reactions were reported.

Liqui-Vict 2X™ NADA 200-007, Original approval, October 30, 1996; sponsor Happy Jack, Inc.; species: Dogs; foi_id 951; FDA PDF

Indication

Removal of large roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala) in dogs and puppies; prevention of T. canis reinfection in puppies, adult dogs and lactating bitches after whelping.

Dose regimen

1 teaspoonful (5 mL) per 10 pounds body weight, oral (suspension), single labeled dose (as pioneer Nemex-2), each mL contains 4.54 mg pyrantel base as pyrantel pamoate; bioequivalence studies dosed 0.5 mL per pound

Labeled Dosage: 1 teaspoonful (5 mL) for each 10 pounds of body weight

Effectiveness

Bioequivalence (clinical end-point) study: controlled anthelmintic test vs pioneer Nemex-2 in dogs with natural Ancylostoma caninum infection, two replicates, blinded, necropsy 7 days post-treatment; a separate critical test for Toxocara canis (8 Liqui-Vict, 7 Nemex-2, 6 control dogs analyzed); n = 30; primary endpoint: percent efficacy from worm counts at necropsy (controlled test) / expelled vs retained worms (critical test); result: A. caninum: Liqui-Vict 2X 98.8% vs Nemex-2 92.5% (10 dogs each, controls 166.2 mean worms); T. canis critical test: 83.75% vs 78.25% (controls 11%), one-sided equivalence hypotheses rejected (p = 0.04135, p = 0.0166); products concluded bioequivalent

Test Animals: 30 dogs of mixed breed, random size and ages, and both sexes were used in this study.

Extraction notes: Generic (ANADA); relies on pioneer NADA 100-237 for target animal safety (no study, target_animal_safety null). Effectiveness recorded is the clinical end-point bioequivalence study. Dogs were observed daily for adverse reactions; none were reported.