Tepoxalin

Nonsteroidal Anti-inflammatory Drug (NSAID) Dual cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog Oral 10-20 mg/kg Once daily (q24h) Duration: Variable; typically 7-14 days for acute conditions, long-term for chronic osteoarthritis
Notes: Administer with food to reduce gastrointestinal upset. Use the lowest effective dose for the shortest duration. Tablets are scored for dose adjustment.

Clinical Indications & Species Uses

General Indications
  • Pain and inflammation associated with musculoskeletal disorders
Dog (Canine)
  • Management of pain and inflammation associated with osteoarthritis
  • Control of postoperative pain and inflammation

Pharmacology & Mechanism of Action

Drug Class: Nonsteroidal Anti-inflammatory Drug (NSAID) | Pharmacological Group: Dual cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor

Mechanism of Action: Tepoxalin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits both cyclooxygenase (COX) and lipoxygenase (LOX) pathways. It preferentially inhibits COX-2 over COX-1, reducing the synthesis of pro-inflammatory prostaglandins while sparing gastroprotective prostaglandins. Additionally, inhibition of LOX reduces leukotriene production, which contributes to its anti-inflammatory and analgesic effects. The dual inhibition may provide enhanced anti-inflammatory activity and potentially reduce gastrointestinal toxicity compared to selective COX-2 inhibitors alone.

Pharmacodynamics: Tepoxalin produces dose-dependent anti-inflammatory, analgesic, and antipyretic effects. It reduces inflammation and pain associated with musculoskeletal disorders such as osteoarthritis. Its dual COX/LOX inhibition may also modulate leukocyte function and reduce the production of inflammatory mediators. The onset of action is typically within hours, with peak effects observed after several days of continuous therapy.

⚡ Pharmacokinetics Summary

Absorption: Tepoxalin is rapidly and well absorbed after oral administration in dogs. Peak plasma concentrations are achieved within 1-2 hours. Food may delay absorption but does not significantly affect overall bioavailability.
Distribution: Tepoxalin is highly protein-bound (>99%) and distributes widely into tissues, with high concentrations in synovial fluid, which is beneficial for joint inflammation. It crosses the blood-brain barrier to a limited extent.
Metabolism: Tepoxalin undergoes extensive hepatic metabolism. It is rapidly converted to an active metabolite, RWJ-20142, which also possesses COX/LOX inhibitory activity. The parent drug and metabolite are further metabolized via oxidation and conjugation.
Excretion: Tepoxalin and its metabolites are excreted primarily in the feces (approximately 60-70%) and to a lesser extent in urine (30-40%). Biliary excretion is a major route for the parent drug and metabolites.
Half-Life: In dogs, the elimination half-life of tepoxalin is approximately 1.5-2 hours, but its active metabolite has a longer half-life of about 12-24 hours, allowing for once-daily dosing.
Bioavailability: Oral bioavailability is high, approximately 80-90% in dogs.
Protein Binding: Tepoxalin is extensively bound to plasma proteins (>99%), primarily albumin.

Available Formulations & Strengths

Oral Tablet 50 mg, 100 mg, 200 mg (Oral)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to tepoxalin or other NSAIDs
  • Active gastrointestinal ulceration or bleeding
  • Renal or hepatic impairment
  • Concurrent use of other NSAIDs or corticosteroids
  • Pregnancy, especially during late gestation
  • Lactating animals (safety not established)
Warnings & Clinical Precautions:
  • Use with caution in dogs with pre-existing renal, hepatic, or cardiac disease
  • Monitor for signs of gastrointestinal toxicity (vomiting, diarrhea, melena)
  • Use with caution in dehydrated, hypovolemic, or hypotensive animals
  • Not recommended for use in cats due to lack of safety data
  • Avoid use in animals with bleeding disorders
  • Do not exceed recommended dose or duration
  • Use with caution in young or geriatric animals

Adverse Effects & Reactions

Common:

  • Vomiting
  • Diarrhea
  • Decreased appetite
  • Lethargy

Serious / Severe:

  • Gastrointestinal ulceration and perforation
  • Renal toxicity (acute renal failure)
  • Hepatic toxicity
  • Bleeding disorders

Rare:

  • Idiosyncratic hepatotoxicity
  • Blood dyscrasias
  • Neurological signs (ataxia, seizures)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other NSAIDs (e.g., carprofen, meloxicam) Increased risk of gastrointestinal ulceration and renal toxicity High
Corticosteroids (e.g., prednisone) Increased risk of gastrointestinal ulceration and perforation High
Anticoagulants (e.g., warfarin, heparin) Increased risk of bleeding due to platelet inhibition High
Diuretics (e.g., furosemide) Reduced renal perfusion and increased risk of renal toxicity Moderate
ACE inhibitors (e.g., enalapril) Reduced renal function and increased risk of renal toxicity Moderate
Aminoglycoside antibiotics Increased risk of nephrotoxicity Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Gastrointestinal bleeding
  • Lethargy
  • Loss of appetite
  • Renal failure
  • Seizures
  • Coma

Emergency Treatment Protocol: Induce emesis if within 2 hours of ingestion. Administer activated charcoal to reduce absorption. Provide symptomatic and supportive care, including intravenous fluids to maintain renal perfusion, gastroprotective agents (e.g., sucralfate, H2 antagonists, proton pump inhibitors), and monitoring of renal and hepatic function. In severe cases, hemodialysis may be considered.

Food Animal Withdrawal Times

Tepoxalin is not approved for use in food-producing animals. Withdrawal times are not established. Do not use in animals intended for human consumption.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F)

Handling & Special Conditions: Protect from moisture. Keep in a tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved by FDA for use in dogs (Zubrin®).

Extra-Label (Off-Label) Use: In the US, tepoxalin is approved for use in dogs only. Extra-label use in other species is permitted under AMDUCA only with a valid veterinary-client-patient relationship and appropriate withdrawal times established by the veterinarian. However, due to lack of safety data, extra-label use is discouraged.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Tepoxalin is a dual COX/LOX inhibitor that provides effective pain relief and anti-inflammatory effects for canine osteoarthritis. It is administered once daily due to the long half-life of its active metabolite. While it may offer advantages over selective COX-2 inhibitors in terms of gastrointestinal safety, it still carries risks of GI ulceration and renal toxicity. It should be used with caution in animals with risk factors. Regular monitoring of renal and hepatic function is recommended during long-term therapy. Tepoxalin is not approved for cats or other species, and its use in these animals is not recommended.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)