NSAIDs are used for analgesic, antipyretic and anti-inflammatory properties. They produce most of their therapeutic effects
through inhibition of prostaglandin synthesis. There is some evidence that they produce analgesic effects by central mechanisms
other than inhibition of prostaglandin synthesis. In most instances, they have good oral bioavailability, making the oral
route of administration a feasible alternative. There are significant differences in clearance between animal species and
age groups. They have therapeutic indexes that are relatively close to their toxic indexes. For these reasons, extrapolation
of drug dosage regimens between species can be dangerous.
Of the NSAIDs commonly used in large-animal practice, only two are approved for use in food animals. These are flunixin meglumine
and aspirin. Flunixin meglumine has gone through the Food and Drug Administration's (FDA) approval process for use in food-producing
animals. Aspirin is "generally regarded as safe and efficacious" (GRAS and GRAE) by the FDA and was grandfathered in as an
approved compound for food animals. Other veterinary products used in an extra-label manner in food animals are phenylbutazone
and ketoprofen. Dipyrone use in food animals is prohibited.
Aspirin is considered effective for fever and for minor joint/muscle pain. Higher doses are required on a per kg basis in
ruminants compared to other species due to a high clearance and a low volume of distribution. The current labels have no withdrawal
times listed, but the Food Animal Residue Avoidance Databank (FARAD) previously recommended a 24-hour slaughter and milk withdrawal.
Flunixin meglumine is approved for pain in horses, but not cattle. It is approved for use in beef and lactating dairy cattle
for fever and inflammation associated with respiratory disease and endotoxemia. The approved dose is 1.1 mg/kg (BID) -2.2
(SID) mg/kg IV for up to three days. The label slaughter and milk withdrawal times are four days and 36 hours, respectively.
This dose has not been evaluated for its pain-relief effectiveness.
Phenylbutazone is not approved for use in food-producing animals and is prohibited for use in dairy cattle older than 20 months.
Since flunixin meglumine is approved for use in food animals, even though not necessarily for pain, and aspirin is GRAS and
GRAE, these should be considered first. However, many practitioners consider phenylbutazone a superior analgesic for chronic
osteoarthritis. Phenylbutazone has a long half-life in cattle (about 30-80 hours) compared to other large-animal species including
goats and sheep (half-life of about 15-20 hours). Due to the long half-life, a loading dose is required to reach therapeutic
levels more quickly. The recommended dose in cattle based on pharmacokinetic and clinical trials in lame bulls is 17-25 mg/kg
loading dose, followed by 4-6 mg/kg once a day, or 10-14 mg/kg every other day. My clinical experience is that the once-daily
dosage regimen is more effective for pain control than every other day. The long half-life dictates the use of extended withdrawal
times. Past recommendations for slaughter withdrawal were of a minimum 45 days for the first dose, with another five days
added for each day of therapy beyond the first. A one-month course of phenylbutazone at this withdrawal would be more than
six months. Since phenylbutazone poses serious human-health risks, and a very long withdrawal period, make this a drug to
use with extreme caution. If used at all, phenylbutazone should be reserved for valuable beef breeding stock with chronic
osteoarthritis where slaughter is not an option (for example, temporary relief of pain for embryo or semen collection followed
by euthanasia and carcass disposal).
Ketoprofen is not approved for use in food animals and offers no benefits over flunixin meglumine. It should be avoided in
Gastrointestinal (GI) ulceration is the most commonly described side effect of NSAID therapy, but it is rare in animals that
are eating. The first sign of GI trouble is anorexia followed by mild diarrhea, which should subside when the NSAID is discontinued.
Renal toxicity has been described following NSAID administration. Most often, this only occurs in severely hypovolemic animals
or in those receiving other potentially nephrotoxic drugs concurrently. As long as animals are rehydrated before or immediately
after administration, nephrotoxicity should not be a concern.
Other considerations for pain management
Analgesic therapy is a critical part of pain management, especially if the animal is in enough pain to prevent it from eating.
However, when pain is managed in animals with severe musculoskeletal injuries, excessive movement should be controlled with