Trisiden, Trimethoprim/ Sulfadiazine Equine Oral paste

Introduction to Trisiden Equine Oral Paste

Overview of Trisiden and Its Dual-Antibiotic Formulation

Trisiden is a veterinary-grade antimicrobial oral paste uniquely formulated for equine use. It combines two potent antibiotics—Trimethoprim and Sulfadiazine—to deliver broad-spectrum bactericidal activity. This dual-action approach disrupts bacterial survival mechanisms at multiple levels, enhancing treatment efficacy.

Role in Modern Equine Veterinary Medicine

Widely prescribed in equine medicine, Trisiden plays a pivotal role in treating systemic and localized infections. Its efficacy against a broad array of bacterial pathogens makes it indispensable in the management of infectious diseases affecting racehorses, breeding stock, and pleasure animals alike.

Benefits of Oral Paste Delivery System in Horses

- Easy administration with minimal stress to the horse - Uniform dosing accuracy - Improved compliance in horses reluctant to swallow tablets or capsules

Regulatory Status and Veterinary Prescription Requirement

Trisiden is a prescription-only veterinary medicine (POM-V), approved in numerous jurisdictions for equine use. A licensed veterinarian must assess the horse and issue the prescription prior to administration.

Composition and Formulation Details

Active Ingredients: Trimethoprim and Sulfadiazine

Each gram of Trisiden paste contains a synergistic combination of: - Trimethoprim: a dihydrofolate reductase inhibitor - Sulfadiazine: a sulfonamide bacteriostatic agent

Concentration and Ratio of Components

The formulation typically includes a 1:5 ratio of Trimethoprim to Sulfadiazine, a proven combination that ensures maximum bacterial inhibition.

Inactive Ingredients and Excipients

- Palatable base for oral administration - Stabilizers to maintain antibiotic potency - Viscosity agents to ensure uniform dispersion

Pharmacological Classification and Synergistic Effect

Trisiden belongs to the antimicrobial class of potentiated sulfonamides. The combination achieves a synergistic effect by inhibiting successive steps in the folic acid synthesis pathway, thereby enhancing bacterial kill rates.

Mechanism of Action: How Trimethoprim/Sulfadiazine Works in Horses

Inhibition of Bacterial Folic Acid Synthesis

Trimethoprim targets dihydrofolate reductase, while sulfadiazine inhibits dihydropteroate synthase. Together, they block folic acid synthesis required for DNA replication.

Sequential Blockade of Bacterial Metabolic Pathways

- Sulfadiazine halts the early stage of folate synthesis - Trimethoprim acts on the subsequent step, leading to a cumulative inhibition - This dual blockade prevents bacterial proliferation and survival

Spectrum of Antimicrobial Activity

Effective against: - Gram-positive bacteria such as *Streptococcus equi* - Gram-negative bacteria including *Escherichia coli* and *Salmonella* spp.

Time- and Concentration-Dependent Effects

While sulfadiazine’s effect is concentration-dependent, trimethoprim exhibits time-dependent activity—resulting in sustained antimicrobial pressure across dosing intervals.

Approved Veterinary Uses of Trisiden Paste

Respiratory Tract Infections

Treats bacterial bronchitis, pneumonia, and *Streptococcus equi* (strangles).

Urinary Tract Infections

Indicated in infections of the kidneys, ureters, bladder, and urethra.

Gastrointestinal Infections

Used in the treatment of *Salmonella* and *Clostridium* infections causing colitis.

Wound Infections and Abscesses

Supports recovery from infected lacerations and post-traumatic abscesses.

Skin and Soft Tissue Bacterial Infections

Effective in cellulitis, dermatitis, and secondary bacterial skin involvement.

Off-Label and Investigational Uses in Equines

Use in Post-Surgical Prophylaxis

Administered prophylactically to prevent postoperative infections in orthopedic and abdominal surgeries.

Empirical Therapy in Febrile Horses

Used when a definitive pathogen is not yet identified but systemic infection is suspected.

Treatment of Sepsis or Bacteremia in Foals

In certain neonatal sepsis cases, Trisiden is chosen due to its broad antimicrobial coverage.

Potential Application in Protozoal Infections

Though primarily antibacterial, emerging data suggests occasional utility in treating protozoal infections when used adjunctively.

Dosage and Administration Guidelines for Horses

Standard Dosage Based on Body Weight

Typical dosage: 15-30 mg/kg of combined drug per day, divided into two doses.

Frequency and Duration of Treatment

- Usually administered twice daily - Duration: 5–10 days depending on severity and clinical response

Oral Paste Administration Techniques

- Administer directly into the horse’s mouth using a dosing syringe - Ensure the horse does not spit out the medication

Dosage Adjustment in Foals or Senior Horses

- Foals may require lower or more frequent doses due to immature metabolism - Geriatric horses with reduced renal clearance need adjusted dosing intervals

Missed Dose and Overdose Handling

- If a dose is missed, administer as soon as remembered - In case of overdose: watch for signs of toxicity and contact a veterinarian immediately

Side Effects and Adverse Reactions in Horses

Overview of Known Adverse Reactions

While generally well-tolerated, adverse events may occur with prolonged or high-dose usage.

Common Gastrointestinal Side Effects

- Anorexia - Diarrhea - Mild colic symptoms

Skin Reactions and Hypersensitivity

- Urticaria (hives) - Pruritus (itching) - Rash and localized swelling

Hematological Changes with Prolonged Use

- Thrombocytopenia - Anemia - Leukopenia

Renal Complications and Crystaluria

Sulfadiazine may precipitate in renal tubules, especially in dehydrated horses.

Common and Mild Side Effects to Monitor

Temporary Appetite Suppression

Transient reduction in feed intake may be observed during initial treatment days.

Mild Dehydration Signs

Reduced water intake or dry mucous membranes should be addressed promptly.

Lethargy and Behavioral Changes

Watch for signs such as reduced activity or reluctance to move.

Oral Paste Intolerance and Salivation

Some horses may resist paste administration or exhibit excessive salivation.

Warnings and Contraindications

Contraindicated in Horses with Known Sulfa or Trimethoprim Allergies

Hypersensitive horses should not receive Trisiden due to the risk of severe allergic reaction.

Avoid Use in Horses with Impaired Renal or Hepatic Function

These animals may have reduced drug clearance, heightening toxicity risk.

Risk of Colitis in Adult Horses—Use with Caution

Sulfonamide use has been linked to colitis and enterocolitis in some adult horses.

Not for Use in Animals Intended for Human Consumption

Residues from Trimethoprim/Sulfadiazine may pose a health hazard in meat-producing animals.

Drug Interactions and Compatibility

Interaction with Other Sulfonamides or Antifolate Agents

Concurrent use of Trisiden with other sulfonamide antibiotics or antifolate compounds can potentiate toxicity or lead to overlapping adverse effects. Such combinations may amplify hematologic suppression or hypersensitivity reactions, necessitating vigilant monitoring.

Reduced Efficacy When Combined with Antacids or Certain Feed Supplements

Administration alongside calcium, magnesium, or aluminum-based antacids, as well as iron supplements or mineral-rich feeds, may interfere with the gastrointestinal absorption of Trisiden. This may result in subtherapeutic serum levels and reduced antimicrobial efficacy.

Potential Antagonism with Local Anesthetics or Methotrexate

- Certain local anesthetics may compete with sulfonamides at the enzymatic level, diminishing antibacterial activity. - Methotrexate, a folate antagonist, can synergize with Trimethoprim, increasing the risk of pancytopenia and nephrotoxicity.

Monitoring When Used Concurrently with Nephrotoxic Drugs

Combining Trisiden with nephrotoxic agents such as aminoglycosides or NSAIDs increases the likelihood of renal impairment. Creatinine and BUN levels should be regularly monitored during coadministration.

Precautions and Careful Administration Considerations

Necessity of Culture and Sensitivity Testing When Possible

Prior to initiating treatment, bacterial culture and antibiotic sensitivity testing are advisable to confirm the organism’s susceptibility. This promotes judicious antimicrobial stewardship and minimizes the risk of resistance.

Importance of Hydration to Avoid Crystal Formation in Urine

Sulfadiazine can precipitate in renal tubules, particularly in dehydrated horses. Adequate water intake or supplemental fluid therapy is essential to maintain renal perfusion and prevent crystalluria.

Monitoring of CBC and Renal Parameters During Extended Use

- Complete blood count (CBC) should be monitored periodically to detect anemia, leukopenia, or thrombocytopenia. - Serum chemistry panels are necessary for evaluating renal function during prolonged therapy.

Adjustments for Horses with a History of Colic or Metabolic Disorders

Horses with predisposing gastrointestinal or metabolic conditions may require reduced dosing or closer observation, as they may be more vulnerable to drug-induced GI upset or electrolyte imbalances.

Use in Special Equine Populations

12.1 Administration in Elderly Horses

Age-Related Pharmacokinetic Considerations

Aging horses often exhibit decreased hepatic metabolism and renal clearance, potentially altering the pharmacokinetics of Trimethoprim/Sulfadiazine.

Adjusted Dosing Based on Renal Clearance

Dose frequency or quantity should be reduced in geriatric horses with suboptimal renal filtration to avoid drug accumulation and toxicity.

Increased Susceptibility to Dehydration and Toxicity

Older equines may be less efficient at maintaining hydration, which can compound the risk of sulfonamide-induced renal damage. Hydration status must be assessed regularly.

12.2 Administration in Pregnant and Lactating Mares

Risk Assessment Based on Trimester

While limited data is available, use in early gestation is generally avoided due to potential interference with embryonic folate metabolism. Risk-benefit evaluation should be individualized.

Potential Teratogenicity and Placental Transfer

Both active compounds can cross the placental barrier. Though rare, teratogenic effects are possible, particularly if administered during organogenesis.

Residue Risk in Milk and Suckling Foals

Trace residues may be excreted in mare’s milk, posing a potential risk to nursing foals. Veterinary oversight is essential if treatment during lactation is unavoidable.

12.3 Administration in Foals and Juvenile Horses

Safety Profile in Neonatal and Weanling Foals

Trisiden should be used cautiously in foals under two months of age due to immature liver enzyme systems and developing renal function.

Recommended Starting Age and Dosage Adjustments

Veterinarians typically initiate therapy in foals older than four weeks, adjusting the dose based on body weight and metabolic maturity.

Monitoring Growth and Development During Treatment

Long-term or repeated courses may necessitate evaluation of weight gain, bone density, and general growth parameters to ensure no adverse developmental effects.

Overdose and Toxicity Management in Horses

Symptoms of Trimethoprim/Sulfadiazine Overdose

Clinical signs may include: - Severe anorexia - Ataxia or incoordination - Oral ulceration - Hematuria and dehydration

Emergency Veterinary Procedures

Immediate discontinuation of the drug is essential. Activated charcoal or gastric lavage may be considered if ingestion was recent. Early intervention improves prognosis.

Supportive Care and Fluid Therapy

- IV fluids to promote renal excretion - Electrolyte balancing and monitoring of acid-base status - Antihistamines or corticosteroids in cases of hypersensitivity

Prognosis Following Acute or Chronic Overdose

Mild cases typically resolve with supportive care, while severe toxicity may lead to renal failure or death if untreated. Prognosis depends on the promptness of care.

Storage Instructions and Product Stability

Recommended Storage Temperature Range

Store Trisiden at 15°C to 25°C (59°F to 77°F). Avoid freezing or exposure to extreme heat.

Protection from Light and Moisture

Keep the paste in its original packaging, away from direct sunlight and humidity, to preserve potency and prevent degradation.

Shelf Life and Expiration Considerations

Do not use beyond the expiration date indicated on the label. Compromised paste may exhibit changes in consistency, color, or odor.

Safe Handling and Disposal of Expired Product

Dispose of unused or expired medication in accordance with local veterinary pharmaceutical waste regulations. Do not flush or incinerate without guidance.

Handling Instructions and Owner Safety Precautions

Safe Administration Techniques for Horse Handlers

- Use an appropriate dosing syringe - Stand to the side of the horse’s head to avoid injury - Gently insert the paste behind the molars

Hygiene Practices After Handling Medicated Paste

Wash hands thoroughly with soap and water. Avoid contact with mucous membranes, especially eyes and mouth.

Protective Gear Recommendations

Gloves are recommended for individuals with sensitive skin or when prolonged exposure is anticipated.

Environmental Precautions for Paste Residues

Clean up any spilled paste immediately. Do not allow residues to contaminate water sources or feed troughs to prevent environmental and animal exposure.

Trisiden, Trimethoprim/ Sulfadiazine Equine Oral paste FAQ