Diclofenac Sodium — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.5-1 mg/kg	q12h	Duration: 3-5 days (max 7 days) Notes: Use lowest effective dose; monitor for GI and renal effects.
Dog	IV	1 mg/kg	q24h	Duration: Up to 3 days Notes: Slow IV injection; not approved in all countries.
Cat	PO	0.1-0.2 mg/kg	q24h	Duration: 1-2 days Notes: Extremely narrow safety margin; use only if no alternative; monitor closely.
Horse	PO	1-2 mg/kg	q12h	Duration: 3-5 days Notes: Oral absorption is variable; may cause GI irritation.
Horse	IV	1 mg/kg	q24h	Duration: Up to 5 days Notes: Slow IV administration; monitor renal function.
Cattle	IM	2.5 mg/kg	q24h	Duration: 3 days Notes: Not approved in many countries; withdrawal times must be observed.

Clinical Indications & Species Uses

General Indications

Pain and inflammation associated with musculoskeletal disorders
Post-operative pain management

Dog (Canine)

Post-operative pain and inflammation
Musculoskeletal pain (e.g., osteoarthritis)
Soft tissue inflammation

Horse (Equine)

Musculoskeletal pain and inflammation (e.g., laminitis, myositis)
Post-operative pain

Pharmacology & Mechanism of Action

Drug Class: Nonsteroidal Anti-inflammatory Drug (NSAID) | Pharmacological Group: Acetic acid derivative

Mechanism of Action: Diclofenac sodium is a nonsteroidal anti-inflammatory drug (NSAID) that exerts its effects primarily by inhibiting the cyclooxygenase (COX) enzymes, COX-1 and COX-2, thereby reducing the synthesis of prostaglandins from arachidonic acid. Prostaglandins are key mediators of inflammation, pain, and fever. Diclofenac has a relatively higher selectivity for COX-2 compared to COX-1, but this selectivity is less pronounced than that of coxibs. It also inhibits lipoxygenase pathways and may affect neutrophil chemotaxis, contributing to its anti-inflammatory effects. Additionally, diclofenac may modulate the release of pro-inflammatory cytokines and reduce the production of reactive oxygen species.

Pharmacodynamics: Diclofenac produces analgesic, anti-inflammatory, and antipyretic effects. Its anti-inflammatory potency is generally considered to be greater than that of aspirin, ibuprofen, and phenylbutazone in animal models. The drug reduces prostaglandin synthesis in inflamed tissues, leading to decreased vasodilation, edema, and pain. In veterinary medicine, diclofenac is used for its analgesic and anti-inflammatory properties, particularly in musculoskeletal conditions. Its effects on COX-1 inhibition can lead to gastrointestinal and renal side effects, especially with prolonged use or at high doses.

⚡ Pharmacokinetics Summary

Absorption: Diclofenac is well absorbed after oral administration in most species, with peak plasma concentrations occurring within 1-2 hours in dogs and cats. In horses, oral absorption is slower and may be incomplete. Bioavailability is approximately 60-80% in dogs and cats, but can be reduced by food. Topical absorption is variable and depends on the formulation and skin condition.

Distribution: Diclofenac is highly protein-bound (greater than 99%) in plasma, primarily to albumin. It distributes widely into tissues, including synovial fluid, where concentrations may exceed plasma levels after repeated dosing. It crosses the placenta and is excreted in milk in small amounts. The volume of distribution is relatively small, reflecting its high protein binding.

Metabolism: Diclofenac undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes (CYP2C9 in humans, but species-specific enzymes in animals). It is metabolized to hydroxylated metabolites, which are then conjugated with glucuronic acid or sulfate. Some metabolites retain pharmacological activity. In dogs, the primary metabolic pathway involves hydroxylation and conjugation, while in cats, glucuronidation is deficient, leading to slower metabolism and potential accumulation.

Excretion: Diclofenac and its metabolites are excreted primarily in the urine (about 60-70%) and feces (30-40%). In dogs, approximately 50% of the dose is excreted in urine as conjugates. Biliary excretion and enterohepatic recirculation may occur, contributing to prolonged effects. The elimination half-life varies by species: dogs 1-2 hours, cats 2-4 hours, horses 1-2 hours, cattle 1-3 hours.

Half-Life: Dogs: 1-2 hours; Cats: 2-4 hours; Horses: 1-2 hours; Cattle: 1-3 hours

Bioavailability: Oral: 60-80% in dogs and cats; variable in horses; topical: low systemic absorption

Protein Binding: >99% (primarily albumin)

Available Formulations & Strengths

Oral Tablet 25 mg, 50 mg, 75 mg (PO)

Oral Solution 15 mg/mL (PO)

Injectable Solution 25 mg/mL (IV/IM)

Topical Gel 1% (Topical)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to diclofenac or other NSAIDs
Active gastrointestinal ulceration or bleeding
Renal or hepatic impairment
Dehydration or hypovolemia
Concurrent use of other NSAIDs or corticosteroids
Pregnancy (especially late gestation) unless benefits outweigh risks
Use in cats is contraindicated due to high risk of toxicity

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, hypotensive, or hypovolemic animals
Do not exceed recommended dose or duration
In cats, use is extremely risky; consider alternative analgesics
In food animals, observe withdrawal times
Use lowest effective dose for shortest duration
May cause injection site reactions when given IM

Adverse Effects & Reactions

Common:

Gastrointestinal upset (vomiting, diarrhea, anorexia)
Elevated liver enzymes
Renal effects (increased BUN/creatinine)

Serious / Severe:

Gastrointestinal ulceration and perforation
Acute renal failure
Hepatotoxicity
Bone marrow suppression (rare)
Hypotension (with rapid IV administration)

Rare:

Blood dyscrasias
Allergic reactions (anaphylaxis)
Neurological signs (seizures, ataxia)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Other NSAIDs (e.g., aspirin, carprofen)	Increased risk of gastrointestinal ulceration and renal toxicity	High
Corticosteroids (e.g., prednisone)	Increased risk of GI ulceration and perforation	High
Anticoagulants (e.g., warfarin)	Increased bleeding risk due to platelet inhibition	High
Diuretics (e.g., furosemide)	Reduced diuretic efficacy and increased risk of renal toxicity	Moderate
ACE inhibitors (e.g., enalapril)	Reduced antihypertensive effect and increased renal risk	Moderate
Aminoglycosides	Increased risk of nephrotoxicity	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Vomiting
Diarrhea (possibly bloody)
Lethargy
Ataxia
Seizures
Acute renal failure
Gastrointestinal ulceration
Respiratory depression

Emergency Treatment Protocol: Induce emesis if within 2 hours of ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide supportive care including IV fluids to maintain renal perfusion, protect GI mucosa with gastroprotectants (e.g., sucralfate, H2 antagonists or proton pump inhibitors). Monitor renal and hepatic function. In severe cases, consider hemodialysis or peritoneal dialysis. There is no specific antidote.

Food Animal Withdrawal Times

🥩 Meat: 7 days🥛 Milk: 3 days

Withdrawal times vary by country and formulation; consult local regulations. For cattle, meat withdrawal is typically 7 days and milk 3 days when used extra-label.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (15-30°C) in a tight, light-resistant container.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from moisture and light. Keep out of reach of children and animals.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use in the US; approved in some other countries for dogs and horses.

Extra-Label (Off-Label) Use: In the US, diclofenac is not approved for veterinary use in food animals; extra-label use is permitted under AMDUCA with a valid veterinary-client-patient relationship and extended withdrawal times. In some countries, it is approved for use in dogs and horses. Always follow local regulations.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Diclofenac is a potent NSAID with strong anti-inflammatory and analgesic properties. However, its use in veterinary medicine is limited by a narrow safety margin, particularly in cats, and a higher risk of gastrointestinal and renal adverse effects compared to some other NSAIDs. It should be used with caution, at the lowest effective dose, and for the shortest duration possible. In dogs, it may be used for short-term pain management, but alternatives such as carprofen or meloxicam are often preferred due to better safety profiles. In horses, diclofenac can be used for musculoskeletal pain, but oral absorption is variable and GI irritation is common. Topical formulations may provide local relief with reduced systemic exposure. In food animals, extra-label use is subject to strict regulations and withdrawal times. Always monitor renal and hepatic function during therapy, and avoid concurrent use with other NSAIDs or corticosteroids. Client education is essential to recognize signs of toxicity early.

References & Literature

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