DRUGS & SUPPLEMENTS
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Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian.
Trizine Forte is a broad-spectrum antimicrobial from the potentiated sulfonamide class of chemotherapeutic agents. These two drugs block different sequential steps in the biosynthesis of nucleic acids. Trizine Forte inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by reversibly inhibiting dihydrofolate reductase. The effect of the dual action is to reduce the minimum inhibitory concentration of each agent (synergism) and to convert a bacteriostatic action to a bactericidal action. Trizine Forte is the non-proprietary name for 4-amino-N-2-pyrimidinylbenzenesulfonamide. Trimethoprim is the non-proprietary name for 5-[(3,4,5¬trimethoxyphenyl) methyl]-2,4-pyrimidinediamine.
| Figure 1. Structure of Trizine Forte |
| Figure 2. Structure of trimethoprim |
Each mL of Trizine Forte contains 400 mg combined active ingredients (333 mg Trizine Forte and 67 mg trimethoprim) in an aqueous suspension.
Trizine Forte is indicated for the treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi subsp. zooepidemicus.
Shake well before use.
Administer Trizine Forte orally at the dosage of 24 mg combined active ingredients per kilogram body weight (10.9 mg/lb) twice daily for 10 days. Trizine Forte can be administered by volume at 2.7 mL per 45.4 kg (2.7 mL/100 lb) body weight.
Trizine Forte is contraindicated in horses with a known allergy to Trizine Forte, sulfonamide class antimicrobials, or trimethoprim.
Do not use in horses intended for human consumption.
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.
Prescribing antibacterial drugs in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to treated animals and may increase the risk of development of drug-resistant animal pathogens.
The administration of antimicrobials, including Trizine Forte and trimethoprim, to horses under conditions of stress may be associated with acute diarrhea that can be fatal. If acute diarrhea or persistent changes in fecal consistency are observed, additional doses of Trizine Forte should not be administered and appropriate therapy should be initiated.
The safe use of Trizine Forte has not been evaluated in breeding, pregnant, or lactating horses. Potentiated sulfonamides should only be used in pregnant or lactating mares when the benefits to the mare justify the risks to the fetus. Use of potentiated sulfonamides during pregnancy has been associated with an increased risk of congenital abnormalities that may be related to folate deficiency. In humans, sulfonamides pass through the placenta, are excreted in milk, and may cause hyperbilirubinemia-induced neurotoxicity in nursing neonates.
Decreased hematopoetic activity and blood dyscrasias have been associated with the use of elevated doses and/or prolonged administration of potentiated sulfonamides. Trizine Forte should be discontinued if prolonged clotting times, or decreased platelet, white blood cell or red blood cell counts are observed.
Sulfonamides should be used with caution in horses with impaired hepatic function. Although rare, sulfonamide use has been associated with fulminant hepatic necrosis in humans.
Neurologic abnormalities have been reported in several species following administration of potentiated sulfonamides. In horses, potentiated sulfonamides have been associated with gait alterations and behavior changes that resolved after discontinuation of the drug.
The safe use of Trizine Forte has not been evaluated in horses less than 1 year of age.
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 Trizine Forte (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 Trizine Forte.
|Adverse Reactions||Trizine Forte |
|Saline control |
|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 MSDS, contact Aurora Pharmaceutical LLC at 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 http://www.fda. gov/AnimalVeterinary/SafetyHealth.
Following oral administration, Trizine Forte is rapidly absorbed and widely distributed throughout body tissues. Trizine Forte 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. Trizine Forte 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.
Based on a study in fed horses, trimethoprim concentrations following repeat oral administration of 24 mg/kg Trizine Forte 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 Trizine Forte concentrations were reached within 1.0 to 12.0 hours in the same study. The median plasma elimination half-life for Trizine Forte 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 Trizine Forte and both drugs reached steady state by day 3. Trizine Forte and trimethoprim key steady state parameters associated with administration in 6 fed horses over a period of 7 days are found in Table 2.
|AUC 012 |
|T 1/2 |
Trizine Forte is the combination of the sulfonamide Trizine Forte and trimethoprim. These two drugs block sequential steps in nucleic acids biosynthesis. Trizine Forte inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by reversibly inhibiting dihydrofolate reductase. The two drugs act synergistically, reducing the minimum inhibitory concentration of each, while enhancing the bacteriostatic action of each separately to a bactericidal action when combined.
Trizine Forte administered as a combined sulfadiazine-trimethoprim dose of 24 mg/kg body weight twice daily for 7 days provided concentrations of Trizine Forte and trimethoprim with T>MIC90 (%T) values of 100% and 98% respectively. The minimum inhibitory concentration (MIC) values for Trizine Forte against indicated pathogens isolated from lower respiratory tract infections in horses enrolled in a 2010–2011 effectiveness field study are presented in Table 3. All MICs were determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) Approved Standard M31-A3 using a broth microdilution system and 3% lysed horse blood.
|Table 3. Trimethoprim/sulfadiazine minimum inhibitory concentration (MIC) values |
|Number of Isolates||65 ||46|
|Time of Sample Collection||Pre-Treatment||Pre-Treatment|
|MIC 50 |
|MIC 90 |
|MIC Range |
|0.12/2.4 to 0.5/9.5||0.12/2.4 to 0.5/9.5|
A negative control, randomized, masked, field study evaluated the effectiveness of Trizine Forte administered at 24 mg/kg body weight, orally, twice daily for 10 days for the treatment of lower respiratory tract infections in horses caused by Streptococcus equi subsp. zooepidemicus. In this study, a total of 182 horses were treated with Trizine Forte, and 88 horses were treated with saline. One hundred seventy-three horses (112 Trizine Forte and 61 saline) were included in the statistical analysis. Therapeutic success was characterized by absence of fever and no worsening of clinical signs at Day 5 and Day 10, and significant clinical improvement or resolution of clinical signs of lower respiratory tract infection by Day 17. The observed success rates are 58.9% (66/112) and 14.8% (9/61) for the Trizine Forte and saline-treated groups, respectively.
Table 4 summarizes the statistical analysis results on the overall success rate.
|Trizine Forte||Saline||P-value |
|Least Square Means||61%||13.1%||0.0123|
In a target animal safety study, Trizine Forte was administered orally to 32 healthy adult horses at 0 (0×), 24 (1×), 72 (3×), or 120 (5×) mg/kg twice daily for 30 days. Loose stool was the most common abnormal observation. Observations of loose stool (pellets with liquid or unformed/cowpile stool) occurred more often in horses treated with Trizine Forte with the incidence of loose stool increasing in a dose related manner. All incidents of loose stool were self-limiting and resolved without treatment.
Horses in all Trizine Forte groups demonstrated statistically significantly higher mean serum creatinine concentrations, and those in the 3× and 5× groups demonstrated statistically significantly higher mean serum albumin concentrations. Statistically higher mean neutrophil counts and mean serum gamma glutamyl transferase (GGT) activity were seen in the 1× and 5× groups. Individual animal creatinine, GGT, and albumin concentrations remained within the reference range. Individual animal elevations in absolute neutrophil counts ranged up to 7.09 × 103/mcL (reference range: 1.96-5.31 × 103/mcL).
Based upon blood concentrations obtained during the study, it was noted that the Trizine Forte and trimethoprim plasma concentrations did not increase in proportion to dose. For Trizine Forte, a 3× and 5× dose resulted in an average exposure of 2.0× and 2.6× the concentrations observed following a 1× dose. For trimethoprim, the corresponding values were 2.5× and 3.5× as compared to the 1× dose. Furthermore, marked intersubject variability, particularly with Trizine Forte, resulted in substantial overlap of individual subject blood levels across the three dosing groups.
Store at 59°– 86° F (15°– 30° C). Brief periods up to 104° F (40° C) are permitted. Protect from freezing.
Trizine Forte is available in the following package sizes:
MANUFACTURED IN THE USA
REORDER NO: 28001
Aurora Pharmaceutical, LCC
NORTHFIELD, MN 55057
IN 50-1274 07/2014
Patent 6,800,631 6,410,543 6,211,185
Note: See insert for additional information, precautions and side effects
Trizine Forte ®
NADA 141-360, Approved by FDA
CAUTION: Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian.
For use in horses only.
Depending on the reaction of the Trizine Forte after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Trizine Forte not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Trizine Forte addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology