sulfadiazine

For horses where systemic anti-bacterial action against sensitive organisms is required during treatment of acute strangles, respiratory infections, acute urogenital infections, and wound infections and abscesses

Administer orally once a day, as a single dose for 5 to 7 days. Daily dose may also be halved and given morning and evening. For acute infection therapy continue treatment 2 to 3 days after clinical signs have subsided. If no improvement of acute infection is seen in 3 to 5 days, reevaluate diagnosis. A complete blood count should be done periodically for prolonged use. Not for use in horses intended for food. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Di-Trim® 400 Paste

For control of bacterial infections of horses during treatment of acute strangles, respiratory tract infections, acute urogenital infections, wound infections, and abscesses.

Administer orally in a small amount of feed, as a single daily dose for 5 to 7 days. Continue therapy for 2 to 3 days after clinical signs have subsided. If no improvement is seen in 3 to 5 days, reevaluate diagnosis. A complete blood count should be done periodically for prolonged use. Not for use in horses intended for food. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tucoprim® Powder

For the treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi subsp. zooepidemicus.

For use in horses only. Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

EQUISUL-SDT®

For the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

ReBalance®

The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone or as an adjunct to surgery or debridement with associated infection. The drug is indicated where control of bacterial infection is required during the treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, wound infections, and abscesses.

If no improvement is seen in 3 days, discontinue therapy and reevaluate diagnosis. Administer for 2 to 3 days after symptoms have subsided. Do not treat for more than 14 consecutive days. During long term treatment, periodic platelet counts and white and red blood cell counts are recommended. The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 120 Tablets

For dogs for treatment of acute urinary tract infections, acute bacterial complications of distemper, acute respiratory tract infections, acute alimentary tract infections, and acute septicemia due to Streptococcus zooepidemicus.

Administer once every 24 hours, or for severe infections after an initial dose, administer half the normal daily dose every 12 hours. Continue therapy 2 to 3 days after clinical signs of infection have subsided. If no improvement is seen in 3 to 5 days, reevaluate diagnosis. Injection may be used alone or in conjunction with oral dosing. Not recommended for use for more than 14 days. A complete blood count should be done for prolonged use. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 24% Injection

UNIPRIM POWDER FOR HORSES is indicated in horses where potent systemic antibacterial action against sensitive organisms is required. UNIPRIM POWDER FOR HORSES is indicated where control of bacterial infections is required during treatment of: Acute Strangles Acute Urogenital Infections Respiratory Tract Infections Wound Infections and Abscesses UNIPRIM POWDER FOR HORSES is well tolerated by foals.

UNIPRIM POWDER FOR HORSES

EQUISUL-SDT is indicated for the treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi subsp. zooepidemicus.

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

ReBalance Antiprotozoal Oral Suspension is indicated for the treatment of horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

ReBalance Antiprotozoal Oral Suspension

Following oral administration, EQUISUL-SDT is rapidly absorbed and widely distributed throughout body tissues. Sulfadiazine levels are usually highest in the kidney, while the tissue concentration in other tissues is only slightly lower than plasma concentrations. Concentrations of trimethoprim are usually higher in the lungs, kidney, and liver than in the blood. Sulfadiazine and trimethoprim are both eliminated primarily by renal excretion, both by glomerular filtration and tubular secretion. Urine concentrations of both sulfadiazine and trimethoprim are several-fold higher than blood concentrations.Kahn CM, Line S, eds. The Merck Veterinary Manual. 10th Ed. Merck & Co. 2010. Sulfadiazine and trimethoprim are 20% and 35% bound to plasma protein, respectively. Administration of sulfadiazine and trimethoprim with food has no apparent effect on absorption of sulfadiazine but the absorption of trimethoprim is decreased. Based on a study in fed horses, trimethoprim concentrations following repeat oral administration of 24 mg/kg EQUISUL-SDT to 6 horses reached peak concentration in 0.5 to 12.0 hours. The median plasma elimination half-life was 3 hours, with a range of 2.31 to 4.96 hours. Peak sulfadiazine concentrations were reached within 1.0 to 12.0 hours in the same study. The median plasma elimination half-life for sulfadiazine was approximately 7.80 hours, with a range of 6.78 to 10.39 hours. Only minor accumulation of both drugs was observed following repeat oral administration of EQUISUL-SDT and both drugs reached steady state by day 3. Sulfadiazine and trimethoprim key steady state parameters associated with administration in 6 fed horses over a period of 7 days are found in Table 2. Table 2. Median (Range) of sulfadiazine and trimethoprim pharmacokinetics parameters following repeat dosing of 24 mg/kg bid EQUISUL-SDT for 7 days to six horses in fed condition Drug Sulfadiazine Trimethoprim Tmax (hr) 4.75 (1.0012.00) 8.50 (0.5012.00) Cmax (µg/mL) 17.63 (10.1031.15) 0.78 (0.601.14) AUC 012 (last dose) (hr*µg/mL) 159.35 (73.90282.54) 5.47 (3.3110.91) T 1/2 (hr) 7.80 (6.7810.39) 3.00 (2.314.96)

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

Sulfonamides (a specific group of antimicrobial agents) and pyrimethamine are two different antimicrobial agents which inhibit folic acid synthesis at two different sites, in the same synthetic pathway. The combination of a sulfonamide and pyrimethamine is synergistic with the drug combination having an antiprotozoal effect.

ReBalance Antiprotozoal Oral Suspension

Trimethoprim and sulfadiazine should not be used in horses showing marked liver parenchymal damage, blood dyscrasias, or in those with history of sulfonamide sensitivity.

UNIPRIM POWDER FOR HORSES

The use of ReBalance Antiprotozoal Oral Suspension in contraindicated in horses with known hypersensitivity to sulfonamide drugs or pyrimethamine.

ReBalance Antiprotozoal Oral Suspension

EQUISUL-SDT is contraindicated in horses with a known allergy to sulfadiazine, sulfonamide class antimicrobials, or trimethoprim.

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

Not for use in humans. For use in animals only. Keep this and all drugs out of the reach of children. Consult a physician in the case of accidental human exposure. Antimicrobial drugs, including sulfonamides, can cause mild to severe allergic reactions in some individuals. Avoid direct contact of the product with the skin, eyes, mouth, and clothing. Persons with a known sensitivity to sulfonamides or trimethoprim should avoid exposure to this product. If an allergic reaction occurs (e.g., skin rash, hives, difficulty breathing, facial swelling) seek medical attention.

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

Do not use in horses intended for human consumption. Keep UNIPRIM POWDER FOR HORSES in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

UNIPRIM POWDER FOR HORSES

For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of the reach of children.

ReBalance Antiprotozoal Oral Suspension

Seventy-five horses (37 horses in the 1X group, 38 horses in the 2X group) that were treated with test article for at least 90 days were evaluated for adverse reaction. Bone marrow suppression: Anemia: ReBalance Antiprotozoal Oral Suspension administration caused overall anemia (classification of anemia based on HBC, Hgb, and PCV/HCT values in 12% of the observations in the 1X group and 21% of the 2X group. In the 1X group, anemia was noted in in 22%, leukopenia in 19%, neutropenia in 5% and thrombocytopenia in 3% of the cases. In the 2X group, anemia was noted in 58%, leukopenia in 55%, neutropenia in 29% and thrombocytopenia in 5% of the cases. The incidence of bone marrow suppression in the 2X treatment group was two or more times that of the 1X group and the degree of suppression was more serious (mild to severe vs. mild to moderate). because of these blood dyscrasias, test article was interrupted over four times more often in horses treated at the 2X dosage than those treated 1X, Although both groups were off treatment for about the same amount of time (approximately 20% of the treatment period). In some instances of bone marrow suppression, diet was supplemented with folinic acid. GI: Anorexia was observed in two horses in the 1X group and one hose in the 2X group. One horse in the 1X group and one horse in the 2X group were observed to be off feed. Observation of Anorexia and decreased appetite occurred predominately during the first 90 days of the treatment period. Observation of anorexia/decreased appetite in two of the above-referenced cases were due to unrelated illnesses. Loose stools were observed in three horses in the 1X group and five in the 2X group. The majority of these observations occurred in the first thirty days of treatment . Diarrhea was observed in one horse in the 2X group on Day 4 of the study. The appearance of loose stool/diarrhea observations were self-limiting and resolved without treatment or discontinuation of test article. Brief, mild colic was observed in the three cases (one in the 1X group and two in the 2X group). colic was treated conservatively or not at all and resolved without sequelae. Integument: Urticaria was observed in one horse in the 1X group and two horses in the 2X group. One horse was treated topically, two were untreated. All cases resolved without sequelae. Treatment crisis: (marked worsening of the neurological condition) was reported in one horse in the 1X treatment group. Depression/lethargy was observed infrequently occurred during the early part of the study in both groups and was primarily associated with the EPM syndrome. In one case, depression was associated with acute onset of a liver disorder. Seizure: One horse in the 1X treatment group suffered from seizures. Seizure activity may be associated CNS damage from EPM.

ReBalance Antiprotozoal Oral Suspension

Adverse reactions reported during a field study of 270 horses of various breeds, ranging from 1 to 25 years of age, which had been treated with either EQUISUL-SDT (n = 182) or with a saline control (n = 88) are summarized in Table 1. At least one episode of loose stool of varying severity was observed in 69 of 182 (38%) of the EQUISUL-SDT-treated horses, and 29 of 88 (33%) saline control horses. Of those animals experiencing loose stool, 2 of 182 (1.1%) of the EQUISUL-SDT-treated horses and 0 of 88 (0%) placebo-treated horses were removed from the study due to diarrhea (defined as at least one episode of watery stool). Both cases of diarrhea in this study were self-limiting and resolved without treatment within 5–10 days after discontinuation of EQUISUL-SDT. Table 1. Number of Horses with Adverse Reactions During the Field Study with EQUISUL-SDT Adverse Reactions Equisul-SDT (n=182) Saline control (n=88) Loose stool (including diarrhea) 69 (38%) 29 (33%) Colic 3 (1.6%) 2 (2.2%) Diarrhea 2 (1.1%) 0 (0%) To report suspected adverse events, for technical assistance or to obtain a copy of the SDS, contact Aurora Pharmaceutical, Inc. at 1-888-215-1256 or www.aurorapharmaceutical.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda. gov/reportanimalae.

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

During clinical trials, one case of anorexia and one case of loose feces following treatment with the drug were reported. Individual animal hypersensitivity may result in local or generalized reactions, sometimes fatal. Anaphylactoid reactions, although rare, may also occur. Antidote: Epinephrine. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Neogen Corporation at 859-254-1221 or neogen.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae. Post Approval Experience: Horses have developed diarrhea during trimethoprim and sulfadiazine treatment, which could be fatal. If fecal consistency changes during trimethoprim and sulfadiazine therapy, discontinue treatment immediately and contact your veterinarian.

UNIPRIM POWDER FOR HORSES

Two milliliters (160 milligrams of trimethoprim and 800 milligrams of sulfadiazine) per 100 pounds (45 kilograms) of body weight per day. For intravenous use. Administer as single dose for 5 to 7 days. Daily dose may also be halved and given morning and evening.

Intravenous

Not for use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 48% Injection

Administer 24 mg combined active ingredients per kg body weight (10.9 mg/lb) twice daily for 10 days. EQUISUL-SDT® can be administered by volume at 2.7 mL per 45.4 kg (2.7 mL/100 lb) body weight.

Oral

For use in horses only. Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

EQUISUL-SDT®

Administer orally 20 milligrams sulfadiazine per kilogram body weight and 1 milligram per kilogram pyrimethamine daily or 4 mL oral suspension per 110 lb (50 kg) of body weight once per day.

Oral

Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

ReBalance®

Administer orally as a single dose for 5 to 7 days. 3.75 grams (250 milligrams of trimethoprim and 1,250 milligrams of sulfadiazine) per 110 pounds (50 kilograms) of body weight per day.

Oral

Not for use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 400 Oral Paste

2 milliliters (160 milligrams of trimethoprim and 800 milligrams of sulfadiazine) per 100 pounds (45 kilograms) of body weight per day. For intravenous use.

Intravenous

Administer as single dose for 5 to 7 days. Daily dose may also be halved and given morning and evening. Continue acute infection therapy 2 to 3 days after clinical signs have subsided. If no improvement of acute infections is seen in 3 to 5 days, reevaluate diagnosis. A complete blood count should be done periodically for prolonged use. Not for use in horses intended for food. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Di-Trim® 48% Injection

5 grams (335 milligrams of trimethoprim and 1665 milligrams of sulfadiazine) per 150 pounds (68 kilograms) of body weight per day.

Oral

Administer orally once a day, as a single dose for 5 to 7 days. Daily dose may also be halved and given morning and evening. For acute infection therapy continue treatment 2 to 3 days after clinical signs have subsided. If no improvement of acute infection is seen in 3 to 5 days, reevaluate diagnosis. A complete blood count should be done periodically for prolonged use. Not for use in horses intended for food. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Di-Trim® 400 Paste

3.75 grams per 110 pounds (50 kilograms) of body weight per day.

Oral

Administer orally in a small amount of feed, as a single daily dose for 5 to 7 days. Continue therapy for 2 to 3 days after clinical signs have subsided. If no improvement is seen in 3 to 5 days, reevaluate diagnosis. A complete blood count should be done periodically for prolonged use. Not for use in horses intended for food. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tucoprim® Powder

The drug is given orally at 30 milligrams per kilogram of body weight per day (14 milligrams per pound per day), or as follows: 2.2 pounds body weight- 1 30 milligram tablet 4.4 pounds body weight- 2 30 milligram tablets 6.6 pounds body weight- 3 30 milligram tablets 8.8 pounds body weight- 4 30 milligram tablets Up to 9 pounds body weight- 1 120 milligram tablet 10 to 19 pounds body weight- 2 120 milligram tablets 20 to 29 pounds body weight- 3 120 milligram tablets 30 to 40 pounds body weight- 4 120 milligram tablets 30 to 40 pounds body weight- 1 480 milligram tablet 40 to 60 pounds body weight- 1 1/2 480 milligram tablets 60 to 80 pounds body weight- 2 480 milligram tablets 80 to 110 pounds body weight- 3 480 milligram tablets Over 110 pounds body weight- 4 480 milligram tablets The drug is given once daily. Alternatively, especially in severe infections, the initial dose may be followed by one-half the recommended daily dose every 12 hours.

Oral

If no improvement is seen in 3 days, discontinue therapy and reevaluate diagnosis. Administer for 2 to 3 days after symptoms have subsided. Do not treat for more than 14 consecutive days. During long term treatment, periodic platelet counts and white and red blood cell counts are recommended. The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 120 Tablets

The drug is given orally at 30 milligrams per kilogram of body weight per day (14 milligrams per pound per day), or as follows: 30 milligram tablets 2.2 pounds body weight- 1 tablet 4.4 pounds body weight- 2 tablets 6.6 pounds body weight- 3 tablets 8.8 pounds body weight- 4 tablets 120 milligram tablets Up to 9 pounds body weight- 1 tablet 10 to 19 pounds body weight- 2 tablets 20 to 29 pounds body weight- 3 tablets 30 to 40 pounds body weight- 4 tablets 480 milligram tablets 30 to 40 pounds body weight- 1 tablet 40 to 60 pounds body weight- 1 1/2 60 to 80 pounds body weight- 2 tablets 80 to 110 pounds body weight- 3 tablets Over 110 pounds body weight- 4 tablets

Oral

The drug is given once daily. Alternatively, especially in severe infections, the initial dose may be followed by one-half the recommended daily dose every 12 hours. If no improvement is seen in 3 days, discontinue therapy and reevaluate diagnosis. Administer for 2 to 3 days after symptoms have subsided. Do not treat for more than 14 consecutive days. During long term treatment, periodic platelet counts and white and red blood cell counts are recommended. The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Di-Trim® Tablets

One milliliter (40 milligrams of trimethoprim and 200 milligrams of sulfadiazine) per 20 pounds (9 kilograms) of body weight per day. For subcutaneous use.

Subcutaneous

Administer once every 24 hours, or for severe infections after an initial dose, administer half the normal daily dose every 12 hours. Continue therapy 2 to 3 days after clinical signs of infection have subsided. If no improvement is seen in 3 to 5 days, reevaluate diagnosis. Injection may be used alone or in conjunction with oral dosing. Not recommended for use for more than 14 days. A complete blood count should be done for prolonged use. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 24% Injection

1 milliliter (10 milligrams of trimethoprim and 50 milligrams of sulfadiazine) per 5 pounds of body weight.

Oral

For oral use only. Administer the recommended dose once daily or one-half the recommended daily dose every 12 hours. Administer for 2 to 3 days after symptoms have subsided. If no improvement is seen in 3 days, discontinue therapy and reevaluate diagnosis. Do not treat for more than 14 consecutive days. During long-term treatment, a complete blood count is recommended. The drug should not be used in patients showing marked liver parenchymal damage or blood dyscrasia, nor in those with a history of sulfonamide sensitivity. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Tribrissen® 60 Oral Suspension

The recommended dose is 3.75 g UNIPRIM POWDER FOR HORSES per 110 lbs (50 kg) body weight per day. Administer UNIPRIM POWDER FOR HORSES orally once a day in a small amount of palatable feed. Dose Instructions: One 37.5 g packet is sufficient to treat 1100 lbs (500 kg) of body weight. For the 200 g, 400 g, and 1200 g jars, and 2000 g pail, two level, loose-filled, 32 cc scoops contain 37.5 g, sufficient to treat 1100 lbs (500 kg) of body weight. Since product contents may settle, gentle agitation during scooping is recommended. The usual course of treatment is a single, daily dose for 5 to 7 days. Continue acute infection therapy for 2 or 3 days after clinical signs have subsided. If no improvement of acute infections is seen in 3 to 5 days, reevaluate the diagnosis. UNIPRIM POWDER FOR HORSES may be used alone or in conjunction with intravenous dosing. Following treatment with trimethoprim and sulfadiazine 48% injection, therapy can be maintained using oral Powder. A complete blood count should be done periodically in patients receiving UNIPRIM POWDER FOR HORSES for prolonged periods. If significant reduction in the count of any formed blood element is noted, treatment with UNIPRIM POWDER FOR HORSES should be discontinued.

ORAL

UNIPRIM POWDER FOR HORSES

Shake well before use. Administer EQUISUL-SDT orally at the dosage of 24 mg combined active ingredients per kilogram body weight (10.9 mg/lb) twice daily for 10 days. EQUISUL-SDT can be administered by volume at 2.7 mL per 45.4 kg (2.7 mL/100 lb) body weight. For 280 mL and 560 mL bottles with draw-off cap: Remove cap. Peel off white foil backed bottle seal and replace cap. Peel off outer cap seal exposing (hole) opening. Push an oral tip syringe into the cap opening. Invert and draw out appropriate volume of EQUISUL-SDT solution. (Note: Do not remove syringe while the bottle is inverted as possible spillage may result.) Detach syringe and administer orally at the dosage of 24 mg combined active ingredients per kilogram body weight (10.9 mg/lb) twice daily for 10 days. EQUISUL-SDT can be administered by volume at 2.7 mL per 45.4 kg (2.7 mL/100 lb) body weight.

ORAL

EQUISUL-SDT® (Sulfadiazine/Trimethoprim)Oral Suspension

ReBalance Antiprotozoal Oral Suspension is to be administered at a dose of 20 mg/kg sulfadiazine and 1 mg/kg pyrimethamine daily or 4 mL of ReBalance Antiprotozoal Oral Suspension per 110 lb. (50 kg) of body weight once per day. The duration of treatment is dependent upon clinical response, but the usual treatment regimen ranges from 90 to 270 days. Administer orally by suitable dosing syringe at least one hour prior to feeding with hay or grain. Insert nozzle of syringe through the interdental space and deposit the dose on the back of the tongue by depressing the plunger. Shake well before use.

ORAL

ReBalance Antiprotozoal Oral Suspension