Phenylbutazone

Non-Steroidal Anti-Inflammatory Drug (NSAID) Pyrazolone derivative

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 10-15 mg/kg q8h Duration: 3-5 days (max 7 days)
Notes: Use with caution; safer alternatives preferred. Reduce dose in elderly or debilitated animals.
Horse IV 4.4 mg/kg (2 g per 450 kg) Once daily Duration: 3-5 days; may be repeated after 48 hours if needed
Notes: Administer slowly IV. Oral dosing: 4.4 mg/kg q12h for 1 day, then 2.2 mg/kg q12h.
Horse PO 4.4 mg/kg q12h for 1 day, then 2.2 mg/kg q12h Duration: 3-5 days
Notes: Oral paste or powder. Do not use in horses intended for human consumption.
Cattle IV 10-20 mg/kg Once daily Duration: Up to 3 days
Notes: Extra-label use; observe withdrawal times. Not approved for use in lactating dairy cattle.
Cattle PO 10-20 mg/kg q12-24h Duration: Up to 3 days
Notes: Extra-label use; observe withdrawal times.
Small Ruminants (Sheep/Goats) PO 10-20 mg/kg q12-24h Duration: Up to 3 days
Notes: Extra-label use; observe withdrawal times.

Clinical Indications & Species Uses

General Indications
  • Treatment of inflammatory conditions, pain, and fever in large animals, especially horses; used off-label in some species
Dog (Canine)
  • Musculoskeletal pain and inflammation
  • Osteoarthritis
  • Soft tissue inflammation
  • Post-operative pain (less common due to availability of safer NSAIDs)
Horse (Equine)
  • Musculoskeletal pain and inflammation
  • Lameness
  • Soft tissue injuries
  • Post-operative pain
  • Fever reduction
Cattle (Bovine)
  • Pain and inflammation associated with respiratory disease
  • Mastitis
  • Musculoskeletal disorders
  • Fever reduction
Small Ruminants (Sheep / Goat)
  • Pain and inflammation (off-label use)
  • Musculoskeletal disorders

Pharmacology & Mechanism of Action

Drug Class: Non-Steroidal Anti-Inflammatory Drug (NSAID) | Pharmacological Group: Pyrazolone derivative

Mechanism of Action: Phenylbutazone is a non-selective inhibitor of cyclooxygenase (COX) enzymes, thereby blocking the conversion of arachidonic acid to prostaglandins and thromboxanes. This reduces the production of pro-inflammatory mediators, leading to anti-inflammatory, analgesic, and antipyretic effects. It also has some uricosuric activity.

Pharmacodynamics: Phenylbutazone produces potent anti-inflammatory effects, moderate analgesic effects, and antipyretic activity. It is more effective in treating inflammatory conditions than in acute pain. Its effects are mediated by inhibition of prostaglandin synthesis, which also contributes to its adverse effects on the gastrointestinal tract and kidneys.

⚑ Pharmacokinetics Summary

Absorption: Rapidly and completely absorbed after oral administration. Peak plasma concentrations occur within 2-6 hours in most species. Bioavailability is high (near 100%) for oral formulations.
Distribution: Widely distributed throughout the body. It is highly bound to plasma proteins (98-99%), primarily albumin. It penetrates well into inflamed tissues and synovial fluid. It crosses the placenta and is excreted in milk.
Metabolism: Extensively metabolized in the liver, primarily by hydroxylation to oxyphenbutazone, which is also pharmacologically active. Other metabolites include gamma-hydroxyphenylbutazone. Metabolism can be species-specific.
Excretion: Excreted primarily in the urine as metabolites and unchanged drug. Biliary excretion also occurs, with enterohepatic recirculation. The elimination half-life varies significantly among species.
Half-Life: Dog: 3.5-6 hours; Horse: 3.5-6 hours; Cattle: 2-4 hours; Cat: 4-6 hours (but prolonged due to slow metabolism); Rabbit: 1-2 hours.
Bioavailability: Oral: ~100% in most species; IM: variable, but generally good.
Protein Binding: 98-99% bound to plasma proteins, primarily albumin.

Available Formulations & Strengths

Oral Tablet 100 mg, 200 mg, 400 mg, 500 mg, 1 g (PO)
Oral Paste 200 mg/mL (e.g., 6 g/30 mL syringe) (PO)
Injectable Solution 200 mg/mL (20% solution) (IV)
Oral Powder Various concentrations (e.g., 1 g per scoop) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to phenylbutazone or other NSAIDs
  • Gastrointestinal ulcers or bleeding
  • Renal or hepatic impairment
  • Blood dyscrasias (e.g., anemia, leukopenia)
  • Pregnancy (especially late gestation) unless benefits outweigh risks
  • Concurrent use of other NSAIDs or corticosteroids
  • In cats: generally contraindicated due to high toxicity risk
Warnings & Clinical Precautions:
  • Use with caution in animals with pre-existing renal, hepatic, or cardiac disease
  • Monitor for signs of gastrointestinal toxicity (vomiting, diarrhea, melena)
  • Avoid use in dehydrated or hypotensive animals
  • Use the lowest effective dose for the shortest duration
  • In horses, prolonged use may cause oral ulcers, gastrointestinal disturbances, and kidney damage
  • In cattle, extra-label use requires a valid veterinary-client-patient relationship and extended withdrawal times
  • Do not administer intra-arterially or perivascularly (severe tissue irritation)
  • In dogs, use only when safer alternatives are not available

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea)
  • Loss of appetite
  • Lethargy
  • Oral ulcers (in horses)

Serious / Severe:

  • Gastrointestinal ulceration and perforation
  • Renal papillary necrosis
  • Hepatotoxicity
  • Blood dyscrasias (aplastic anemia, agranulocytosis)
  • Protein-losing nephropathy

Rare:

  • Allergic reactions (anaphylaxis)
  • Bone marrow suppression
  • Stevens-Johnson syndrome

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other NSAIDs (e.g., flunixin, aspirin) Increased risk of gastrointestinal ulceration and renal toxicity High
Corticosteroids Increased risk of gastrointestinal ulceration and perforation High
Anticoagulants (e.g., warfarin) Increased risk of bleeding due to platelet inhibition and protein binding displacement High
Aminoglycoside antibiotics Increased risk of nephrotoxicity Moderate
Diuretics (e.g., furosemide) Reduced diuretic efficacy and increased risk of renal toxicity Moderate
Methotrexate Increased methotrexate toxicity due to reduced renal clearance Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea (possibly bloody)
  • Depression
  • Ataxia
  • Seizures
  • Renal failure
  • Hepatic failure
  • Coma

Emergency Treatment Protocol: Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal. Provide supportive care: IV fluids, gastrointestinal protectants (e.g., sucralfate), antiemetics, and monitoring of renal and hepatic function. In severe cases, consider hemodialysis or peritoneal dialysis.

Food Animal Withdrawal Times

πŸ₯© Meat: 30 daysπŸ₯› Milk: 4 days

Withdrawal times vary by country and formulation. In the US, phenylbutazone is not approved for use in female dairy cattle 20 months of age or older. For horses, it is prohibited in food animals. Always follow local regulations.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25Β°C, excursions permitted to 15-30Β°C).

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep container tightly closed. Do not freeze injectable solutions.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and horses in the US. Not approved for cats, cattle, or other species, but may be used extra-label.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, but requires extended withdrawal times. Phenylbutazone is prohibited for use in female dairy cattle 20 months of age or older. In horses, it is not approved for use in animals intended for human consumption.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Phenylbutazone is a potent NSAID primarily used in horses for musculoskeletal pain and inflammation. It is also used in dogs, but safer alternatives (e.g., carprofen, meloxicam) are preferred. Due to its potential for serious adverse effects, especially gastrointestinal and renal toxicity, it should be used with caution and at the lowest effective dose for the shortest duration. In food animals, extra-label use is restricted and requires strict adherence to withdrawal times. Monitoring for adverse effects is essential, especially during prolonged therapy. It is contraindicated in cats due to high toxicity risk.

References & Literature

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