Chemistry - Naproxen is a propionic acid derivative, and has similar structure and pharmacologic profiles as ibuprofen and ketoprofen. It is a white to off-white crystalline powder with an apparent pKa of 4.15. It is practically insoluble in water and freely soluble in alcohol. The sodium salt is also available commercially for human use.
Storage/Stability/Compatibility - Naproxen should be stored in well-closed, light resistant containers and stored at room temperature. Temperatures above 40° C (104°F) should be avoided.
Pharmacology - Like other NSAIDs, naproxen exhibits analgesic, anti-inflammatory, and antipyrexic activity probably through its inhibition of cyclooxygenase with resultant impediment of prostaglandin synthesis.
Pharmacokinetics - In horses, the drug is reported to have a 50% bioavailability after oral dosing and a half-life of approximately 4 hours. Absorption does not appear to be altered by the presence of food. It may take 5-7 days to see a beneficial response after starting treatment. Following a dose, the drug is metabolized in the liver. It is detectable in the urine for at least 48 hours in the horse after an oral dose.
In dogs, absorption after oral dosing is rapid and bioavailability is between 68-100%. The drug is highly bound to plasma proteins. The average half-life in dogs is very long at 74 hours.
In humans, naproxen is highly bound to plasma proteins (99%). It crosses the placenta and enters milk at levels of about 1% of those in serum.
Uses/Indications - The manufacturer lists the following indications: “.... for the relief of inflammation and associated pain and lameness exhibited with myositis and other soft tissue diseases of the musculoskeletal system of the horse.” (Package Insert; Equiproxen®—Syntex). It has also been used as an antiinflammatory/analgesic in dogs for the treatment of osteoarthritis and other musculoskeletal inflammatory diseases (see adverse reactions below).
Contraindications/Precautions - Naproxen is relatively contraindicated in patients with a history of, or preexisting hematologic, renal or hepatic disease. It is contraindicated in patients with active GI ulcers or with a history of hypersensitivity to the drug. It should be used cautiously in patients with a history of GI ulcers, or heart failure (may cause fluid retention). Animals suffering from inflammation secondary to concomitant infection, should receive appropriate antimicrobial therapy.
In studies in rodents and in limited studies in horses, no evidence of teratogenicity or adverse effects in breeding performance have been detected following the use of naproxen. However, the potential benefits of therapy must be weighed against the potential risks of its use in pregnant animals.
Adverse Effects/Warnings - Adverse effects are apparently uncommon in horses. The possibility exists for GI (distress, diarrhea, ulcers), hematologic (hypoproteinemia, decreased hematocrit), renal (fluid retention) and CNS (neuropathies) effects.
Reports of GI ulcers and perforation associated with naproxen has occurred in dogs. Dogs may also be overly sensitive to the adverse renal effects (nephritis/nephrotic syndrome) and hepatic (increased liver enzymes) effects with naproxen. Because of the apparent very narrow therapeutic index and the seriousness of the potential adverse reactions that can be seen in dogs, many clinicians feel that the drug should not be used in this species.
Overdosage - There is very limited information regarding acute overdoses of this drug in humans and domestic animals. The reported oral LD50 in dogs is >1000 mg/kg. Treatment should follow standard overdose procedures (empty gut following oral ingestion, etc.). Animal studies have demonstrated that activated charcoal may bind significant amounts of naproxen. Supportive treatment should be instituted as necessary. Because naproxen may cause renal effects, monitor electrolyte and fluid balance carefully and manage renal failure using established guidelines.
One report of a dog who received 5.6 mg/kg for 7 days has been published (Gilmour and Walshaw 1987). The dog presented with symptoms of melena, vomiting, depression, regenerative anemia, and pale mucous membranes. Laboratory indices of note included, neutrophilia with a left shift, BUN of 66 mg/dl, serum creatinine of 2.1 mg/dl, serum protein:albumin of 4.0:2.1 g/dls. The dog recovered following treatment with fluids/blood, antibiotics, vitamin/iron supplementation, oral antacids and cimetidine.
Drug Interactions - Because naproxen is highly bound to plasma proteins and may displace other highly bound drugs, increased serum levels and duration of actions of phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory agents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agents can occur. If naproxen is used concurrently with warfarin, enhanced hypoprothrombinemic effects have not been noted, but because of the tendency of naproxen to induce GI bleeding it should be used cautiously in patients on warfarin therapy. When aspirin is used concurrently with naproxen, plasma levels of naproxen may decrease as well as an increased likelihood of GI adverse effects (blood loss) developing. Concomitant administration of aspirin with naproxen is not recommended.
Probenicid may cause a significant increase in serum levels and half-life of naproxen.
Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate; use together with extreme caution. Naproxen may reduce the saluretic and diuretic effects of furosemide. Use with caution in patients with severe cardiac failure.
a) 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) bid for up to 14 consecutive days. (Package Insert; Equiproxen® - Syntex Animal Health)
Monitoring Parameters -
1) Analgesic/anti-inflammatory efficacy
2) GI: appetite, feces (occult blood, diarrhea)
3) PCV (packed cell volume), hematocrit if indicated or on chronic therapy
4) WBC’s if indicated or on chronic therapy
Client Information - Notify veterinarian if symptoms of GI distress (anorexia, vomiting in dogs, diarrhea, black feces or blood in stool) occur, or if animal becomes depressed.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Naproxen 10% (100 mg/ml) Veterinary Solution for Injection; 2 gm vial with 19 ml vial of sterile water for injection. Use entire contents immediately after reconstituting. Makes 20 ml of 10% (100 mg/ml) solution.; Equiproxen® (Fort Dodge); (Rx) Approved for us in horses not intended for food.
Naproxen Veterinary Granules; Each 8 gram packet contains 4 grams of naproxen. Cartons of 14 - 8 gram packets; Equiproxen® (Fort Dodge); (Rx) Approved for us in horses not intended for food.
Naproxen Oral tablets (scored) 250 mg, 375 mg, 500 mg; Naprosyn® (Syntex); Generic (Rx)
Naproxen Oral Suspension 125 mg/5 ml in pints; Naprosyn® (Syntex); Generic (Rx)
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