Chickens: Safe-Guard® AquaSol is indicated for the treatment and control of adult Ascaridia galli in broiler chickens and replacement chickens and for the treatment and control of adult A. galli and Heterakis gallinarum in breeding chickens and laying hens.

Swine: Safe-Guard® AquaSol is indicated for swine, except for nursing piglets, for the treatment and control of: Lungworms: Adult Metastrongylus apri, Adult Metastrongylus pudendotectus; Gastrointestinal worms: Adult and larvae (L3, L4 stages, liver, lung, intestinal forms) large roundworms (Ascaris suum); Adult nodular worms (Oesophagostomum dentatum, O. quadrispinulatum); Adult small stomach worms (Hyostrongylus rubidus); Adult and larvae (L2, L3, L4 stages - intestinal mucosal forms) whipworms (Trichuris suis), and Kidney worms: Adult and larvae Stephanurus dentatus.

Chickens: Safe-Guard® AquaSol must be administered orally to chickens via the drinking water at a daily dose of 1 mg/kg BW (0.454 mg/lb) for 5 consecutive days.

Swine: Safe-Guard® AquaSol must be administered orally to swine via the drinking water at a daily dose of 2.2 mg/kg BW (1 mg/lb) for 3 consecutive days.

Consult your veterinarian for assistance in the diagnosis, treatment, and control of parasitism.

Chickens:

Swine:

Chickens: Six pivotal dose confirmation studies and five field effectiveness studies were conducted to evaluate the effectiveness of Safe-Guard® AquaSol oral suspension against adult A. galli in broiler chickens and replacement chickens and against A. galli and H. gallinarum in breeding chickens and laying hens. Safe-Guard® AquaSol was administered orally in drinking water at 1 mg fenbendazole/kg body weight/day for 5 consecutive days. The chickens were necropsied 7 to 8 days after the last treatment, and adult worms in the intestines and ceca of the chickens in the control and treated groups were counted to determine percent efficacy.

Three dose confirmation studies were conducted in European Union (EU), using 105 Rhode Island Red breed hens (2 years old) for each study. In all three studies, the efficacy against A. galli (97.9%, 97.3%, and 93.9%) and H. gallinarum (99.8%, 96.9%, and 97.3%) was greater than 90%. A fourth dose confirmation study was conducted in the United States (US) using 264 Rhode Island Red breed hens (12 months old). In the study, the efficacy against adult A. galli and H. gallinarum was 98.7% and 99.2%, respectively. A fifth dose confirmation study was conducted in the US using 176 Cobb breed broiler chickens (4 to 5 weeks old). In the study, the efficacy against adult A. galli was 99.4%. A sixth dose confirmation study was conducted in the US using 176 Ross breed broiler chickens (4 to 5 weeks old). In the study, the efficacy against adult A. galli was 100%.

A field effectiveness study was conducted in the EU in a flock of 13,244 Hy-Line layer breed replacement chickens (13 weeks old). Fifteen chickens were necropsied before treatment initiation, and 15 chickens were necropsied seven days after treatment for worm counts. The efficacy against adult A. galli was 90.2%. A second field effectiveness study was conducted in the US using 550 Ross breed broiler chickens (4 to 5 weeks old). The efficacy against adult A. galli was 100%. A third field effectiveness study was conducted in the US using 550 White Leghorn breed replacement chickens (14 weeks old). The efficacy against adult A. galli and H. gallinarum was 100% and 88.9%, respectively. A fourth field effectiveness study was conducted in the US using 550 Cobb breed breeder hens (63 weeks old). The efficacy against adult A. galli and H. gallinarum was 97.6% and 95.3%, respectively. A fifth effectiveness study was conducted in the US using 550 Cobb breed broiler chickens (4 to 5 weeks old). The efficacy against adult A. galli was 100%.

The pivotal dose confirmation studies and field effectiveness studies demonstrated substantial evidence of effectiveness of Safe-Guard® AquaSol at the dose of 1 mg fenbendazole/kg body weight/day for 5 consecutive days against adult A. galli in broiler chickens and replacement chickens and against adult A. galli and H. gallinarum in breeding chickens and laying hens.

Swine: A multi-site, masked, negative-controlled dose confirmation field study was conducted to provide substantial evidence of the effectiveness of Fenbendazole (FBZ) Suspension (20% w/v) administered orally in drinking water to pigs for three consecutive days to provide a dose of 2.2 mg FBZ/kg body weight daily against the dose-limiting worm Trichuris suis (T. suis). A common protocol was implemented in two different geographical locations and with two different investigators.

Weaned, growing-finishing pigs of approximately 6 weeks of age were used in the study. Each study site selected pigs from one source herd verified to be free of T. suis infection. Barrow and gilt breeds representative of U.S. commercial production were used. Housing, management, and husbandry procedures were typical of commercial production practice. A complete feed, adequate to meet the nutritional needs of the study animals, was offered to the animals in self-feeders throughout the study. The feed did not contain antibiotics, anthelmintics, or any other medication.

Fifty-six days prior to treatment administration, all suitable study candidates were orally dosed with approximately 4000 embryonated T. suis eggs. A natural field isolate of T. suis collected in April 2010 from a sow located on a commercial farrow to wean operation located in the U.S. was used. Individual fecal samples were obtained from each candidate animal 46, 47, and 48 days after T. suis inoculation and analyzed for the presence of T. suis eggs. Animals with at least two fecal examinations positive for T. suis eggs were eligible for inclusion in the study.

In each study, 24 healthy pigs were randomized to two treatment groups (FBZ treated and non-medicated) by first blocking by weight in blocks of 4 pigs each and within each weight block, fecal egg count (FEC) in blocks of 2 pigs. The two pigs with the two lowest FEC counts within a weight block were randomized one per treatment group and the two pigs with the highest FEC counts within a weight block were randomized one per treatment group. The two animals assigned to the same treatment group within the same weight block were then assigned to the same pen. Six pens of 2 pigs each were used per treatment group.

Non-medicated water consumption of the pigs in each treatment pen was measured prior to treatment administration to estimate the amount of water required for dosing on each day of the treatment period. The amount of FBZ Suspension administered in drinking water to the study pigs was calculated from pre-treatment body weights. Medicated water was prepared on each treatment day by diluting FBZ Suspension in drinking water to provide a daily dose of 2.2 mg FBZ/kg body weight to the FBZ treated group. The control group received non-medicated drinking water.

Only two pigs at the Minnesota (MN) site that were treated with FBZ had abnormal post-treatment observations ("loose stools"). These two pigs had exhibited abnormal fecal consistency prior to treatment with FBZ. There were no abnormal observations made at the California (CA) site on pigs after FBZ administration. There were no abnormal post-treatment observations attributed to administration of FBZ at either study site. The study animals were euthanized after either 8 or 9 days following the last FBZ administration for retrieval of the large intestinal tract. Adult T.suis worms attached to the tract and in the contents of the tract were counted.

Adequacy of infection was demonstrated at both study sites by having more than 6 non-medicated pigs (11 of the 12 non-medicated animals in MN and 9 of the 12 non-medicated animals in CA) with adult T. suis worm counts of 100 or more per animal.

There was a significant treatment effect in T. suis worm counts between medicated and non-medicated treatment groups at each study site (p=0.0006 in MN and p=0.0003 in CA). The percent reduction in T. suis worm counts in the FBZ medicated animals was greater than 90% (98.5% in MN and 98.6% in CA) compared to the non-medicated animals using transformed data (geometric means).

Chickens: Two margin of safety studies (growing broiler chickens and laying hens at peak egg production) and one reproductive safety study (broiler breeder chickens) were conducted. These studies supported the safety of Safe-Guard® AquaSol in broiler chickens, replacement chickens, laying hens and breeding chickens when administered in drinking water at 1 mg fenbendazole/kg body weight/day for 5 consecutive days.

The margin of safety in broiler chickens was conducted in 480 broiler chickens. Safe-Guard® AquaSol was administered orally as medicated drinking water to three groups of 120 chickens (60 male and 60 female in each group) at 1, 3, and 5 mg fenbendazole/kg body weight/day (1, 3, and 5 times the recommended label dose) for 15 consecutive days (3 times the recommended duration). Another group of 120 chickens (60 male and 60 female) was provided non-medicated drinking water and used as a control group. In all chickens, feed and water intake, body weights, clinical health, and mortality were recorded. Hematology and clinical chemistry parameters were evaluated in 24 chickens from each group. At the end of the treatment phase, gross necropsies were performed on 48 chickens from each group, and organs weights were evaluated. Histopathologic examinations were performed on 48 chickens each from the control and 5 mg fenbendazole/kg body weight groups. No clinically significant effects related to the administration of Safe Guard® AquaSol were observed for any of the parameters evaluated.

The margin of safety in laying hens was conducted in 144 laying hens. Safe-Guard® AquaSol was administered orally as medicated drinking water to three groups of 36 hens at 1, 3, and 5 times the recommended label dose (1, 3, and 5 mg fenbendazole/kg body weight/day) for 15 consecutive days (3 times the recommended duration). Another group of 36 hens was provided non-medicated drinking water and used as a control group. In all hens, feed and water intake, body weights, clinical health, mortality, egg production, and egg quality parameters (including egg shell thickness and strength, egg weight, and Haugh unit) were evaluated. Hematology and clinical chemistry parameters were evaluated in 12 hens from each group. At the end of the treatment phase, gross necropsies were performed on 12 hens from each group, and organs weights were evaluated. Histopathologic examinations were performed on 12 hens each from the control and 5 mg fenbendazole/kg body weight groups. No clinically significant effects related to the administration of Safe-Guard® AquaSol were observed for any of the parameters evaluated.

The reproductive safety in broiler breeding chickens was conducted in 220 broiler breeder chickens. Safe-Guard® AquaSol was administered orally as medicated drinking water to a group of 110 breeding chickens (10 male and 100 female) at 3 mg fenbendazole/kg body weight/day (3 times the recommended label dose) for 21 consecutive days (4 times the recommended duration). Another group of 110 breeding chickens (10 male and 100 female) were provided non-medicated drinking water and used as a control group. The parameters evaluated in the study included feed and water intake, body weights, clinical health, egg production and weight, fertility, hatchability, and 14-day old chick viability. Necropsy of unhatched eggs was performed to record the percentage of dead embryos and dead and culled hatchlings. At the end of the treatment phase, 30 breeding chickens (10 male and 20 female) from each group were necropsied; and gross pathology and weights of testes and female reproductive tracts were evaluated. Histopathologic evaluations were performed on the gross lesions collected during the necropsy. No clinically significant effects related to the administration of Safe-Guard® AquaSol were observed for any of the parameters evaluated.

Swine: Animal safety was established using a combination of swine pharmacokinetic, physiologic, and pharmacologic data that provided a basis for bridging the safety data of Safe-Guard® Type A medicated article (NADA 131-675) to Safe-Guard® AquaSol oral suspension in swine.