Naproxen
Naproxen is a **nonsteroidal anti-inflammatory drug (NSAID)** belonging to the propionic acid class, structurally similar to ibuprofen and ketoprofen. * **Veterinary Use**: Its use in veterinary medicine has been largely superseded by newer, safer, and more COX-2 selective NSAIDs. * **Toxicity Risk**: It is notoriously toxic to dogs due to its exceptionally long half-life (74 hours) and extensive enterohepatic recirculation, leading to a very narrow therapeutic index. Many clinicians strongly advise against its use in dogs. * **Equine Use**: Previously used for musculoskeletal pain, myositis, and soft tissue diseases in horses, but the veterinary-specific product (Equiproxen®) is no longer marketed in the USA.
Mechanism: Naproxen exerts its analgesic, anti-inflammatory, and antipyretic effects by inhibiting the **cyclooxygenase (COX)** enzymes. * **Arachidonic Acid** → **COX-1 and COX-2** inhibition → Decreased synthesis of **prostaglandins** and **thromboxanes**. * The reduction in pro-inflammatory prostaglandins mitigates inflammation, pain, and fever. * Because naproxen is a **non-selective COX inhibitor**, it also blocks the constitutive, protective prostaglandins (via COX-1) in the gastric mucosa and kidneys. This mechanism explains its high propensity for causing gastrointestinal ulceration and renal toxicity, particularly in sensitive species like dogs and cats.
Dosing by species
- Myositis and soft tissue diseases of the musculoskeletal system · 5 mg/kg by slow IV, then 10 mg/kg, PO (top dressed in feed) twice daily for up to 14 days or 10 mg/kg, PO (top dressed in feed) twice daily for up to 14 consecutive days. · IV, PO · q12h · Up to 14 days · ARCI UCGFS Class 4 Drug. Veterinary product no longer commercially available.
- Systemic therapies for joint disease · 10 mg/kg PO daily · PO · q24h
- Septic arthritis pain; inflammation (Rabbits) · 2.4 mg/mL in drinking water for 21 days · PO · Continuous · 21 days · Dose specific to rabbits.
- Osteoarthritis and musculoskeletal inflammatory diseases (Last resort) · 2 mg/kg PO every other day (q48h) · PO · q48h · Because of the difficulty in accurately dosing naproxen and its potential for adverse effects, use only when FDA-approved and safer NSAIDs have been ineffective.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Active GI ulcers
- History of hypersensitivity to naproxen or other NSAIDs
- Pre-existing hematologic, renal, or hepatic disease
Adverse effects
- GI distress (anorexia, vomiting, diarrhea)
- Gastrointestinal ulcers and perforation
- Melena and bloody vomitus
- Renal effects (nephritis, nephrotic syndrome, fluid retention)
- Hepatic effects (increased liver enzymes)
- Hematologic effects (hypoproteinemia, decreased hematocrit, anemia)
- CNS effects (neuropathies, lethargy, depression)
Drug interactions
- Aminoglycosides (gentamicin, amikacin) · Increased risk for nephrotoxicity
- Anticoagulants (heparin, LMWH, warfarin) · Increased risk for bleeding
- Aspirin · Decreased plasma levels of naproxen and increased likelihood of GI adverse effects (blood loss). Concomitant use is not recommended.
- Bisphosphonates (alendronate) · May increase risk for GI ulceration
- Corticosteroids · Concomitant administration significantly increases the risks for GI adverse effects and ulceration
- Furosemide · Naproxen may reduce the saluretic and diuretic effects of furosemide
- Highly protein bound drugs (phenytoin, valproic acid, sulfonamides) · Potential displacement leading to increased serum levels and duration of action of the displaced drug
- Methotrexate · Serious toxicity has occurred; use together with extreme caution
- Probenecid · May cause a significant increase in serum levels and half-life of naproxen
Monitoring
- Analgesic/anti-inflammatory efficacy
- GI signs: appetite, feces (occult blood, diarrhea)
- PCV (packed cell volume) and hematocrit if indicated or on chronic therapy
- WBCs if indicated or on chronic therapy
- Renal and hepatic function panels (especially in dogs)
Overdose
Toxicity is a major concern, particularly in dogs and cats. * **Dogs**: The reported oral LD50 is >1000 mg/kg, but clinical toxicity occurs at much lower doses. * **>5 mg/kg**: Gastrointestinal signs and GI ulceration. * **>25 mg/kg** (some dogs as low as 10 mg/kg): Significant renal damage. * **>50 mg/kg**: Neurologic signs. * **Clinical Signs**: Vomiting (often bloody), lethargy, anorexia, diarrhea, melena, anemia, and elevated renal/hepatic values. * **Treatment**: * **Decontamination**: Emesis and/or activated charcoal if recent ingestion. * **GI Protection**: Misoprostol and sucralfate are recommended for 10-14 days post-exposure. * **Renal Protection**: Fluid diuresis should be considered if renal effects are expected. * **Supportive Care**: Monitor electrolyte and fluid balance carefully; manage renal failure using established guidelines.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.