Non-steroidal anti-inflammatory drugs, or NSAIDs, are a type of medication administered to horses for various conditions. Veterinarians typically prescribe NSAIDs for soft tissue and musculoskeletal injuries, as well as for abdominal inflammation and pain. [1]

Specific conditions in horses that are commonly treated with NSAIDs include degenerative joint disease and colic. [2] NSAIDs can also help relieve fever in horses. [3]

Despite the availability of other types of pain medications, NSAIDs remain the most widely used drugs for pain management in horses. They are popular because they are effective, affordable, and easy to administer. [3]

There are currently six FDA-approved NSAIDs for use in horses, but the three most commonly used NSAIDs include phenylbutazone (Bute), flunixin meglumine (Banamine®), and firocoxib (Equioxx®).

It’s important for horse owners and caretakers to familiarize themselves with the differences between these medications in addition to the correct dosing directions and counter-indications. Although NSAIDs are an effective pain management tool, prolonged use can have long-term health effects in horses.

Always consult a veterinarian if your horse’s pain is not improving, especially if you have been administering NSAIDs for longer than the recommended dosing interval on the package label.

How Do NSAIDs Work

NSAIDs are drugs that reduce inflammation, which is the body’s response to tissue damage. They achieve this by inhibiting the activity of cyclo-oxygenase (COX) enzymes, which are involved in promoting an inflammatory response. [1][4]

COX enzymes are required for the production of prostaglandins, chemicals that cause inflammation, pain, and fever in the horse’s body. When NSAIDs block the activity of COX enzymes, the production of prostaglandins is reduced, resulting in less inflammation.

To date, three COX enzymes have been identified: [2]

  • COX-1
  • COX-2
  • COX-3

Of these three enzymes, COX-1 and COX-2 are best understood; less is known about COX-3. [2]

COX-1 & COX-2 Enzymes

Researchers have identified the following characteristics of COX-1 enzymes: [1]

  • Present in nearly all cell types
  • Act as a “housekeeping” enzyme, playing a role in normal physiological functions to maintain homeostasis
  • Required at low levels for normal gastrointestinal function, blood clotting, and renal (kidney) function

As for COX-2 enzymes, researchers have identified the following characteristics: [1][2]

  • Present in most cell types
  • Normally at very low levels in most tissues, but increase during inflammatory responses by up to 20-fold
  • Play a role in maintaining blood flow in compromised kidneys

Enzyme-Selective NSAIDs

Because NSAIDs work by blocking COX enzymes, there are potentially serious side effects associated with their overuse. For this reason, the benefits of NSAIDs should always be carefully weighed against their potential risks, especially with long-term use. [2]

Most negative effects from NSAIDs are associated with inhibition of COX-1 enzymes. This is likely because COX-1 enzymes have a greater importance in supporting baseline physiology than COX-2 enzymes. [1]

For example, COX-1 enzymes are critical for producing prostaglandins that maintain the stomach’s protective mucus lining, preventing gastric ulcers.

In recent decades, researchers have focused on developing NSAIDs that act selectively against COX-2 enzymes as opposed to COX-1. The goal is to preserve the normal housekeeping functions of COX-1 while inhibiting the pro-inflammatory effects associated with COX-2. [1]

Traditional NSAIDs are nonselective, meaning they inhibit both COX-1 and COX-2 enzymes. Prolonged use of nonselective NSAIDs can increase the risk of negative effects on the gastrointestinal tract and kidneys in horses. [2]

Newer COX-2 selective NSAIDs are less likely to have a negative impact on horses’ overall health. [2][5] That being said, horse owners and caretakers should always seek veterinary guidance before administering NSAIDs for longer than the prescribed dosing interval, regardless of which type is in use.

Phenylbutazone (Bute)

Out of all the NSAIDs used for horses, phenylbutazone (Bute) is most commonly prescribed. [1] It is a non-selective cyclo-oxygenase (COX) inhibitor, meaning it inhibits both COX-1 and COX-2 enzymes.

Common Uses

Bute is often prescribed to treat pain and inflammation associated with chronic lameness and navicular syndrome. [1] Horse owners also often use Bute independently to treat a variety of inflammatory and/or painful musculoskeletal conditions.

Although Bute isn’t commonly used for colic, it is sometimes administered prophylactically to prevent symptoms of endotoxemia, which is a potential complication of colic surgery. [2]

Formulations and Dosing

Bute comes in different formulations including oral tablets, powder, and paste which are easy for horse owners to administer at home. Additionally, this NSAID is available as an intravenous (IV) injection for administration by veterinarians.

When administering Bute by mouth, it’s best to give it with food to help prevent stomach upset and mouth or stomach ulcers. [6] It typically takes 1-2 hours for Bute to take effect and the effects may last for up to several days. [6]

For most orthopedic disorders, the recommended dosing of Bute is 2.2 mg/kg of body weight every 12 hours or 4.4 mg/kg every 24 hours. [7] Veterinarians prefer dosing every 12 hours to keep blood concentrations of the drug more stable and prevent sudden increases that may affect kidney and stomach function.

Cautions and Contraindications

As with all medications, using Bute carries some risk of side effects. Bute is usually only associated with side effects when it is given to horses long term and/or at an inappropriately high dose. [6]

Bute may also interact with other drugs and certain supplements. Therefore, it’s important to tell your veterinarian which medications and supplements your horse is currently on before using this NSAID. [6]

Side effects of Bute can include: [1][6]

If Bute is used for longer than the recommended dosing interval on the package or prescription, it can cause stomach or hindgut ulcers. It can also cause damage to the liver or kidneys. [6]

The IV form of Bute should never be injected into muscle as it can cause a serious infection called clostridial myositis, which can be fatal. [8]

Additionally, always use caution when giving Bute to foals or ponies, as they are more likely to develop mouth or stomach ulcers, as well as other complications. [3]

Following the package directions and working with a veterinarian provide the best chance of preventing negative health outcomes associated with equine medications.

 

Fluxinin (Banamine®)

Banamine® is another popular NSAID used by both veterinarians and horse owners. It is also a non-selective COX inhibitor, inhibiting both COX-1 and COX-2 enzymes.

Though it works in much the same way that Bute does, it is often used for different conditions. Veterinarians typically use flunixin for internal organ pain and inflammation, as it may have better efficacy for this purpose over Bute. [1]

Common Uses

Fluxinin (Banamine®) is most commonly used to reduce pain related to colic and colitis. [1]

Other uses of Banamine® include: [1][3][9]

  • Relief of fever and inflammation associated with endotoxemia
  • Pain control after arthroscopic surgery
  • Pain control for eye disease such as corneal ulcers or glaucoma

Although Bute is more commonly used to treat orthopedic pain in horses, Fluxinin also provides symptomatic relief for some forms of lameness. [9]

Formulations

Fluxinin is most commonly administered as an IV injection or as an oral paste. Veterinarians discourage owners from attempting to administer IV injections, as the risk of severe complications is high. [6]

In cases of an emergency and if an owner doesn’t have the paste on hand, the liquid injectable form of Banamine® can be squirted directly into the mouth or mixed with food or molasses. [6]

Always contact your veterinarian if your horse is having a medical emergency, even if you have administered medication to avoid further complications.

Fluxinin should take effect within 1-2 hours after administration and may last for up to a few days. It can be used to control pain and inflammation in horses for up to 5 days. [6]

The recommended dosing for Banamine® is 1.1 mg/kg of body weight every 12 hours. [6]

Cautions and Contraindications

Though many horse owners may have injectable fluxinin on hand, this formulation should only be given by a veterinarian due to the dangers of administering it incorrectly. IV Banamine® should never be injected into the neck muscles or arteries.

Artery injections can lead to: [4][9]

  • Hysteria
  • Rapid breathing
  • Weakness
  • Seizures

As with the injectable form of Bute, injectable fluxinin should never be given in the muscle. [8] Likewise, Banamine® should never be mixed with other drugs, as they can have negative interactions with each other. [6]

Although the drug label recommends intramuscular injection, research shows that horses injected with flunixin have a high risk of clostridial myositis. [7] For this reason, veterinarians do not recommend intramuscular injection of this product.

Possible side effects of Banamine® include: [1][6]

  • Pain
  • Localized swelling and stiffness at injection site
  • Muscle damage
  • Sweating
  • Oral or stomach ulcers
  • Lack of appetite
  • Low protein levels in blood (rare)
  • Blood disorders (very rare)
  • Slowed repair mechanisms in injured intestine
  • Reduced intestinal motility

The risk for potential side effects increases if fluxinin is given at higher doses, for a prolonged period of time, or in conjunction with other NSAIDs. [6]

Keep in mind that Banamine® should not be used in horses with the following: [6]

  • Allergy to fluxinin or other NSAIDs
  • Kidney, liver, or blood disorders
  • Stomach ulcers

In addition, do not administer Banamine® to horses who:

  • Have recently been given other NSAIDs
  • Did not experience pain relief with the first dose
  • Have already been on NSAIDs for the maximum dosing interval on the package label

Firocoxib (Equioxx®)

Firocoxib (Equioxx®) is one of the newer NSAIDs on the market. This medication differs from Bute and Banamine® because it is COX-2 selective. This means there are fewer side effects associated with its use. [6]

Common Uses

Equioxx® is commonly used to treat osteoarthritis and has been shown to improve lameness scores. Improvement is usually most noticeable within the first 7 days of use, with a slower rate of improvement afterward. [1][6]

Equioxx® has been shown to reduce joint swelling, joint circumference, and improve range of motion. [1][6]

One study showed that, when compared to oral Bute, oral Equioxx® was more effective at controlling pain and improving function in horses with chronic osteoarthritis. [9]

Another advantage of Equioxx® over Bute and Banamine® relates to small intestine injuries, which can occur in cases of colic. Bute and Banamine® may slow recovery of the protective mucosal layer in horses with intestinal injuries, while Equioxx® does not appear to have this effect. [1]

Formulations

Equioxx® comes as an oral paste, tablet, or injection. It is approved for once daily administration for up to 14 days. Equioxx® can be given with or without food. This NSAID should take effect within 1-2 hours of administration and the effects may last for up to a few days. [6]

The recommended dosage of Equioxx® for oral administration is 0.1 mg/kg of body weight once daily for up to 14 days. [6]

Cautions and Contraindications

Equioxx® should not be given in conjunction with other NSAIDs such as Bute or Banamine®. Always notify your veterinarian of any supplements or herbs your horse is on before giving Equioxx®. [6]

Equioxx® is tolerated well by most horses, but its use does include a risk of side effects such as: [6]

  • Sores or ulcers on the tongue or inside of mouth
  • Sores, scabs, redness, or rubbing of facial skin, especially around the mouth
  • Changes in eating or drinking habits
  • Changes in urination habits
  • Yellowing of gums, skin, or whites of eyes (jaundice)
  • Unexplained weight loss
  • Changes in behavior or activity levels
  • Colic
  • Diarrhea

Equioxx® should not be used in horses with any of these pre-existing conditions: [6]

  • Allergy to NSAIDs
  • Stomach or gastrointestinal ulcers
  • Dehydration
  • Currently on a diuretic treatment such as furosemide
  • Pre-existing kidney, heart, and/or liver problems
  • Pregnant, lactating, or breeding stock
  • Less than one year old
  • Currently on another NSAID, aspirin, or corticosteroids
  • Old, weak, or frail horses

Bute vs. Fluxinin vs. Firocoxib

Table 1. Summary of Bute, Fluxinin, and Firocoxib uses and dosages

Bute Fluxinin (Banamine®) Firocoxib (Equioxx®)
Common Uses Pain and inflammation associated with chronic lameness and navicular syndrome Reduce pain related to colic and colitis. Also used to reduce the adverse effects of endotoxemia Pain and inflammation associated with osteoarthritis
Formulations Tablets, powder, or paste IV injection or oral paste Oral paste, tablet, or injection
Recommended Dosing 2.2 mg/kg body weight every 12 hours or 4.4 mg/kg every 24 hours 1.1 mg/kg body weight every 12 hours 0.1 mg/kg body weight once daily
Maximum Dosing Interval 7 Days 5 Days 14 Days

 

Following the package directions and working with a veterinarian provide the best chance of preventing negative health outcomes associated equine medications.

Side Effects of NSAIDs

NSAIDs are some of the most common medications used by horse owners to control pain and support their horse’s quality of life. The widespread usage of these drugs has led to some concern over their long-term effects.

The most concerning long-term health effects associated with NSAID use are gastric ulcers, kidney damage, and effects on bone remodeling. There is also significant risk of health complications related to using multiple NSAIDs simultaneously.

All medications carry some risk of side effects, so it is important for owners to closely follow the medication label and the advice of their veterinarian to ensure the medication is used as intended.

Gastric Ulcers

Gastric ulcers are the most commonly reported side effect associated with non-selective NSAIDs such as Bute and Banamine.

Gastric ulceration linked to NSAID use is usually attributed to: [1]

  • Overdose
  • Ongoing administration beyond the recommended or prescribed dosing interval
  • Pre-existing risk of ulcers

These ulcers occur due to interference with COX-1 enzymes that maintain the protective mucosal layer of the gastrointestinal tract. [1]

Using a COX-2 selective NSAID such as Equioxx® can help prevent gastric ulceration when given according to the manufacturer’s directions or as prescribed by a veterinarian. [1]

Kidney Damage

Non-selective COX inhibitors also pose a risk of kidney damage. COX-1 enzymes play a role in regulating blood flow to the kidney, ensuring adequate nutrient and oxygen delivery to the tissue.

With NSAID use, inhibition of COX-1 can cause reduced blood flow, potentially resulting in tissue damage. This effect is exacerbated by dehydration, which reduces the available blood volume directed to the kidneys. [10]

In horses that are sufficiently hydrated, COX-1 inhibition from NSAIDs is unlikely to impact kidney function. [1]

Bone Remodeling

Research also shows that COX-2 enzymes are important for bone remodeling, which is the process of bone tissue renewal and repair. Bone remodeling involves the resorption of old bone and the formation of new bone, a cycle essential for maintaining bone strength and integrity.

COX-2 is involved in activation of prostaglandins during bone healing, which stimulate osteoblasts, the main cell type responsible for producing new bone.

Studies show that mice without COX-2 have reduced bone formation after fractures, indicating the importance of COX-2 in bone healing. This has led to questions around the potential impact of using nonselective NSAIDs on bone strength in horses. [11]

The impact of NSAID use on bone healing in horses needs further research. In human medicine, NSAIDs are recommended for fracture patients unless other risk factors might impair bone healing. [11]

Stacking

More concerning side effects of NSAID use occurs when two or more NSAIDs are used together within a short period of time.

This practice is known as “stacking” and can be common in competition and racing. Owners also sometimes administer multiple NSAIDs to horses in treatment for severe orthopedic disorders such as laminitis. [7][9]

With stacking, horses may be given Banamine and Bute only 24 hours apart. This can be problematic because the first drug may not have fully cleared from the horse’s system before the second is administered, increasing the risk of side effects. [7]

Studies show that using two or more NSAIDs at the same time puts horses at increased risk of a number of complications including: [12]

  • Colic
  • Protein loss
  • Diarrhea
  • Gastric ulcers
  • Colitis
  • Kidney damage

Additionally, some horses are much more sensitive to complications from NSAID use than others, further increasing the dangers of stacking. [12]

NSAID Use in Competition Horses

Using any NSAID before competition can mask lameness, putting the horse at risk for catastrophic injury.

Because of this and other risks, gaming commissions and the U.S. Equestrian Federation (USEF) have restricted timing of NSAID use allowed prior to racing or competition. [9] Always check the regulations for your sport before administering medication to your horse.

NSAID Use in Foals

All NSAIDs, including Bute, Banamine, and Equioxx®, should be used with extreme caution in foals. This is especially true for foals that are sick or premature and may have compromised kidney function. [3]

Researchers advise that horse owners avoid use of NSAIDs altogether in foals less than 30 days old. Talk to your veterinarian about alternative forms of pain management instead. [3]

Summary

NSAIDs are medications used to control pain and inflammation related to a variety of conditions in horses, from colic to osteoarthritis. The three most commonly used NSAIDs include Bute, Banamine, and Equioxx®.

  • Bute and Banamine are nonselective NSAIDs, meaning they inhibit both COX-1 and COX-2 enzymes and have highest risk of side effects in horses.
  • The most common side effect related to Bute and Banamine is gastric ulceration.
  • Equioxx® is COX-2 selective, making it a safer choice for some horses. However, this NSAID still comes with the risk of side effects.
  • Most side effects associated with NSAIDs are associated with inappropriate use. Therefore, always follow your veterinarian’s recommendations when using any NSAID with your horse.

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References

  1. Knych, H.K. Nonsteroidal Anti-inflammatory Drug Use in Horses. Vet Clin Equine. 2017. View Summary
  2. Ziegler, A. and Blikslager, A.T. Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic. Equine Vet Education. 2020.
  3. Banse, H.E. and Cribb, A.E. Review of Nonsteroidal Anti-Inflammatory Drug Selection in Horses. Respiratory Medicine. 2015.
  4. Mercer, M.A. et al. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals. 2023.
  5. Ziegler, A. et al. Update on the use of cyclooxygenase 2–selective nonsteroidal anti-inflammatory drugs in horses. J Am Vet Med Assoc. 2017.
  6. Plumb, D. C. Plumb’s Veterinary Drug Handbook. 7th Edition. PharmaVet Inc. 2011.
  7. Knych, H.K. et al. Pharmacokinetics and anti-inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses. Equine Vet Journal. 2019. View Summary
  8. Teixera, R. and Valberg, S. Risks of giving intramuscular banamine to horses. University of Minnesota Extension. 2023.
  9. Jacobs, C.C. et al. Non-steroidal anti-inflammatory drugs in equine orthopaedics. Equine Vet Journal. 2022. View Summary
  10. Hörl, W.H., Nonsteroidal Anti-Inflammatory Drugs and the Kidney. Pharmaceuticals (Basel). 2010.
  11. Pountos. I. et al., Do Nonsteroidal Anti-Inflammatory Drugs Affect Bone Healing? A Critical Analysis. The Scientific World Journal. 2012.
  12. Palmer, S.E. Equine Medical Director Advisory—NSAID Anti-Stacking Rule. New York State Gaming Commission.