Trimatrim

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Trimatrim uses



For use in horses only.

NADA 141-360

CAUTION

Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION

Trimatrim 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. Trimatrim 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. Trimatrim 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 Trimatrim

Figure 2. Structure of trimethoprim


Each mL of Trimatrim contains 400 mg combined active ingredients (333 mg Trimatrim and 67 mg trimethoprim) in an aqueous suspension.

Chemical Structure Chemical Structure

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INDICATION

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

DOSAGE AND ADMINISTRATION

Shake well before use.

Administer Trimatrim orally at the dosage of 24 mg combined active ingredients per kilogram body weight (10.9 mg/lb) twice daily for 10 days. Trimatrim can be administered by volume at 2.7 mL per 45.4 kg (2.7 mL/100 lb) body weight.

CONTRAINDICATIONS

Trimatrim is contraindicated in horses with a known allergy to Trimatrim, sulfonamide class antimicrobials, or trimethoprim.

WARNING

Do not use in horses intended for human consumption.

HUMAN WARNINGS

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.

PRECAUTIONS

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 Trimatrim 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 Trimatrim should not be administered and appropriate therapy should be initiated.

The safe use of Trimatrim 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. Trimatrim 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 Trimatrim has not been evaluated in horses less than 1 year of age.

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ADVERSE REACTIONS

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 Trimatrim (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 Trimatrim.

Adverse Reactions Trimatrim

(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 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.

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CLINICAL PHARMACOLOGY

Following oral administration, Trimatrim is rapidly absorbed and widely distributed throughout body tissues. Trimatrim 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. Trimatrim 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. Trimatrim and trimethoprim are 20% and 35% bound to plasma protein, respectively. Administration of Trimatrim 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 Trimatrim 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 Trimatrim concentrations were reached within 1.0 to 12.0 hours in the same study. The median plasma elimination half-life for Trimatrim 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 Trimatrim and both drugs reached steady state by day 3. Trimatrim and trimethoprim key steady state parameters associated with administration in 6 fed horses over a period of 7 days are found in Table 2.

Drug Trimatrim Trimethoprim
Tmax 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)

MICROBIOLOGY

Trimatrim is the combination of the sulfonamide Trimatrim and trimethoprim. These two drugs block sequential steps in nucleic acids biosynthesis. Trimatrim 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.

Trimatrim administered as a combined sulfadiazine-trimethoprim dose of 24 mg/kg body weight twice daily for 7 days provided concentrations of Trimatrim and trimethoprim with T>MIC90 (%T) values of 100% and 98% respectively. The minimum inhibitory concentration (MIC) values for Trimatrim 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) valuesThe correlation between in vitro susceptibility data and clinical effectiveness is unknown. of isolates recovered from horses with lower respiratory infection caused by Streptococcus equi subsp. zooepidemicus treated with Trimatrim in the U.S. (2010–2011)
Treatment Outcome Success Failure
Number of Isolates 65One isolate of S. equi subsp. zooepidemicus was not tested. 46
Time of Sample Collection Pre-Treatment Pre-Treatment
MIC 50The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.

(µg/mL)

0.25/4.75 0.25/4.75
MIC 90

(µg/mL)

0.25/4.75 0.25/4.75
MIC Range

(µg/mL)

0.12/2.4 to 0.5/9.5 0.12/2.4 to 0.5/9.5
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EFFECTIVENESS

A negative control, randomized, masked, field study evaluated the effectiveness of Trimatrim 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 Trimatrim, and 88 horses were treated with saline. One hundred seventy-three horses (112 Trimatrim 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 Trimatrim and saline-treated groups, respectively.

Table 4 summarizes the statistical analysis results on the overall success rate.

Trimatrim Saline P-valueP-value and estimated success rates are based on back-transformed mean estimates from the statistical analysis.
Least Square Means 61% 13.1% 0.0123

ANIMAL SAFETY

In a target animal safety study, Trimatrim 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 Trimatrim 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 Trimatrim 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 Trimatrim and trimethoprim plasma concentrations did not increase in proportion to dose. For Trimatrim, 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 Trimatrim, resulted in substantial overlap of individual subject blood levels across the three dosing groups.

STORAGE CONDITIONS

Store at 59°– 86° F (15°– 30° C). Brief periods up to 104° F (40° C) are permitted. Protect from freezing.

HOW SUPPLIED

Trimatrim is available in the following package sizes:

135 mL

280 mL

560 mL

900 mL

MANUFACTURED IN THE USA

REORDER NO: 28001

MANUFACTURED BY:

Aurora Pharmaceutical, LCC

NORTHFIELD, MN 55057

888-215-1256

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

NDC 51072-020-00

Trimatrim ®

(Sulfadiazine/Trimethoprim)

Antimicrobial

Oral Suspension

400 mg/mL

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.

900 mL

aurora pharmaceutical®

Trimatrim pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Trimatrim available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Trimatrim destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Trimatrim Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Trimatrim pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."TRIMETHOPRIM TABLET [TEVA PHARMACEUTICALS USA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."SULFADIAZINE TABLET [EON LABS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."SULFADIAZINE SODIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Trimatrim?

Depending on the reaction of the Trimatrim after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Trimatrim 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 Trimatrim 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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Review

sdrugs.com conducted a study on Trimatrim, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Trimatrim consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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