Phenylbutazone
Phenylbutazone (commonly known as **"bute"**) is a classic, non-selective non-steroidal anti-inflammatory drug (NSAID) of the pyrazolone class. **Clinical Pearl:** While historically used across many species for its potent analgesic, anti-inflammatory, and antipyretic properties, its use in modern veterinary medicine is almost exclusively restricted to **equine practice** for the management of musculoskeletal pain (e.g., laminitis, osteoarthritis). In small animals (dogs and cats), it has largely been replaced by safer, COX-2 selective NSAIDs (like carprofen or meloxicam) due to a high risk of severe adverse effects, including blood dyscrasias, hepatotoxicity, and severe gastrointestinal ulceration. It is strictly regulated in food-producing animals due to human safety concerns regarding bone marrow toxicity (aplastic anemia).
Mechanism: Phenylbutazone acts primarily by inhibiting the **cyclooxygenase (COX)** enzymes (both COX-1 and COX-2), which prevents the conversion of arachidonic acid โ **prostaglandins** and **thromboxanes**. * **โ Prostaglandins** โ Reduced inflammation, analgesia, and antipyresis. * **โ Thromboxane A2** โ Decreased platelet aggregation. **Pharmacological Note:** Phenylbutazone is metabolized in the liver to **oxyphenbutazone**, an active metabolite that contributes significantly to its prolonged efficacy (often >24 hours) despite a relatively short plasma half-life. The irreversible binding of phenylbutazone to cyclooxygenase also extends its duration of action. It also possesses mild uricosuric properties.
Dosing by species
- General inflammation/pain ยท 4-8 mg/kg PO or 2-5 mg/kg IV ยท PO or IV ยท Extralabel use prohibited in female dairy cattle 20 months of age or older.
- General inflammation/pain ยท 10-20 mg/kg PO, then 2.5-5 mg/kg q24h or 10 mg/kg every 48 hours PO ยท PO ยท q24h or q48h ยท Extralabel use prohibited in female dairy cattle 20 months of age or older.
- To reduce pain or pyrexia associated with pleuropneumonia ยท 2.2-4.4 mg/kg ยท PO or IV ยท q12h ยท first week of treatment or longer
- General musculoskeletal inflammation ยท 1-2 grams per 454 kg (1000 lb.) horse IV, or 2-4 grams per 454 kg (1000 lb.) horse PO ยท IV or PO ยท daily ยท Limit IV administration to no more than 5 successive days ยท Do not exceed 4 grams/day. Use high end of dosage range initially, then titrate to lowest effective dose. Injection must be made slowly and with care.
- Adjunctive treatment of colic (to reduce endotoxic effects) ยท 2.2 mg/kg ยท PO or IV ยท twice daily
- Adjunctive treatment of laminitis ยท Initial dose of 4 grams, immediately decreased to 1 to 1.5 grams ยท PO or IV ยท twice daily ยท Dose for an average adult-sized horse. Lower dose is used to keep the horse comfortable, but not relieve pain to the extent the horse moves around excessively.
- Osteoarthritis ยท 2.2 mg/kg ยท PO ยท twice daily ยท Minimal dose to control pain.
- General inflammation/pain ยท 4 mg/kg ยท IV or PO ยท q24h
Routes of administration
Contraindications
- Known hypersensitivity to phenylbutazone or other NSAIDs
- History of or preexisting hematologic or bone marrow abnormalities
- Preexisting gastrointestinal ulcers
- Food-producing animals (especially female dairy cattle 20 months of age or older)
- Lactating dairy cattle
- Pre-existing gastrointestinal ulceration
- Renal impairment
- Hepatic impairment
- Hematological disorders
- Use in food-producing animals (banned in many jurisdictions)
Adverse effects
- Gastrointestinal and oral erosions/ulcers
- Hypoalbuminemia (especially in foals/ponies)
- Renal papillary necrosis and azotemia
- Sodium and water retention (edema)
- Blood dyscrasias (agranulocytosis, aplastic anemia)
- Hepatotoxicity
- Severe tissue necrosis and sloughing (if injected IM or SC)
- CNS stimulation and seizures (if injected intracarotid)
- Gastrointestinal ulceration and bleeding
- Bone marrow suppression (aplastic anemia, leukopenia)
- Renal papillary necrosis
- Sodium and water retention
Drug interactions
- Furosemide ยท Phenylbutazone may antagonize the increased renal blood flow effects caused by furosemide.
- Hepatotoxic Drugs ยท Concurrent administration may increase the chances of hepatotoxicity developing.
- NSAIDs ยท Concurrent use increases the potential for adverse GI and renal reactions. (Note: 'Stacking' with ketoprofen shows synergistic toxicity).
- Penicillamine ยท May increase the risk of hematologic and/or renal adverse reactions.
- Penicillin G ยท Phenylbutazone may increase the plasma half-life of penicillin G.
- Sulfonamides ยท Phenylbutazone could potentially displace sulfonamides from plasma proteins, increasing the risk for adverse effects.
- Warfarin ยท Phenylbutazone could potentially displace warfarin from plasma proteins, increasing the risk for bleeding.
- Corticosteroids ยท Increased risk of gastrointestinal ulceration ยท major
- Other NSAIDs ยท Increased risk of gastrointestinal ulceration and renal toxicity ยท major
- Highly protein-bound drugs (e.g., warfarin) ยท Displacement from plasma proteins leading to increased free drug concentrations ยท moderate
Monitoring
- Analgesic, anti-inflammatory, and antipyretic efficacy
- Complete blood counts (CBC) with chronic therapy (weekly early in therapy, biweekly later)
- Urinalysis and renal function parameters (serum creatinine/BUN) with chronic therapy
- Plasma protein determinations (especially in ponies, foals, and debilitated animals)
- Complete Blood Count (CBC)
- Renal function (BUN, Creatinine)
- Liver enzymes
- Clinical signs of GI bleeding (melena)
Overdose
Manifestations of acute overdosage include prompt respiratory or metabolic acidosis with compensatory hyperventilation, seizures, coma, and acute hypotensive crisis. * **Systemic Effects:** Clinical signs of renal failure (oliguric, proteinuria, hematuria), liver injury (hepatomegaly, jaundice), bone marrow depression, and severe GI ulceration/perforation may develop. * **Dogs:** Common signs include ataxia, seizures, tachycardia, trembling, tremors, vomiting, and tachypnea. Oral LD50 is 332 mg/kg. * **Horses:** Common signs include colic, anorexia, and ataxia. **Treatment:** Standard overdose procedures should be followed (e.g., empty gut following oral ingestion). Institute supportive treatment as necessary. Intravenous diazepam can be used to help control seizures. Monitor fluid therapy carefully, as phenylbutazone may cause fluid retention.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.