The following article was generated by the US Food and Drug Administration, the original of which can be found on the FDA website here:
Your 8-year-old yellow Lab Tinker Bell just came in from the backyard and you notice she’s limping on one of her back legs. You check the medicine cabinet in your bathroom to see what medications you have that may help her feel better. You see bottles of aspirin, ibuprofen, naproxen, and acetaminophen—all pain relievers for people. You also have a few tablets of RIMADYL left over from when your other dog had knee surgery. Before reaching for any of the bottles, STOP and call your veterinarian. A pain reliever meant for you or even for your other dog may not be right for Tinker Bell and may even hurt her.
Nonsteroidal Anti-Inflammatory Drugs
With the notable exception of acetaminophen, all the medications listed in the introduction are nonsteroidal anti-inflammatory drugs, commonly called NSAIDs. These drugs are extensively used in both people and animals for their pain relieving, anti-inflammatory, and anti-fever properties. In fact, NSAIDs are the most widely used pain relievers in animals. Veterinarians often prescribe these drugs for dogs with osteoarthritis, a condition where the cartilage – the protective material that cushions a joint - breaks down over time, causing the bones to rub against each other. This rubbing can permanently damage the joint and causes pain, inflammation, and lameness. Veterinarians also often use NSAIDs to manage pain after surgery in both dogs and cats.
The Science—How NSAIDs Work
Nonsteroidal anti-inflammatory drugs mainly target the enzyme cyclooxygenase. An enzyme is a protein made by the body that speeds up a chemical reaction. The enzyme itself remains unchanged during the reaction. Essential to all body functions, enzymes are very specific—each enzyme stimulates a specific reaction that causes a specific result.
In the case of cyclooxygenase (COX), it stimulates cells to produce several substances, including prostaglandins, after the cells are damaged. COX is present in most body tissues, including the gastrointestinal, or digestive, tract (stomach and intestines) and kidneys.
Cell damage occurs → COX is activated → Prostaglandins are produced
Prostaglandins are present throughout the body and have several important functions:
- Contribute to pain, inflammation, and fever;
- Protect the stomach lining from the damaging effects of acid;
- Help maintain blood flow to the kidneys; and
- Support platelet function (platelets are found in the blood of all mammals and help with blood clotting).
Although NSAIDs are a diverse group of drugs, they all work by blocking cyclooxygenase. This leads to fewer prostaglandins being produced, which in turn, reduces ongoing pain, inflammation, and fever. But, NSAIDs also have side effects.
Some of the most common side effects of NSAIDs in animals reported to FDA’s Center for Veterinary Medicine are:
- Decreased to no appetite;
- Decreased activity level; and
Other reported side effects in animals include stomach and intestinal ulcers, stomach and intestinal perforations (holes in the wall of the stomach or intestines), kidney failure, liver failure, and death.
The side effects of NSAIDs are mainly seen in the gastrointestinal tract, kidneys, and liver.
Gastrointestinal (Digestive) Tract
Nonsteroidal anti-inflammatory drugs cause gastrointestinal side effects both directly and indirectly. The direct, or local, effects are related to the drugs’ physical properties. Many NSAIDs are slightly acidic, so they directly irritate the stomach lining. Also, NSAIDs build up in the gastrointestinal tract, leading to direct injury of the stomach cells.
The indirect effects are due to NSAIDs preventing the body from making prostaglandins. With less stomach-protective prostaglandins in the body, the stomach lining is more prone to damage from acid, leading to ulcers and perforations.
Giving an animal two NSAIDs at the same time, or an NSAID with a steroid such as prednisone, increases the risk of gastrointestinal side effects and should be avoided.
During periods of decreased blood flow to the kidneys—such as when an animal is dehydrated, under anesthesia, or has kidney disease—prostaglandins cause the arteries going to the kidneys to open. This helps keep blood flowing to these vital organs. Because nonsteroidal anti-inflammatory drugs block prostaglandins, they reduce blood flow to the kidneys, possibly causing kidney damage and leading to sudden-onset kidney failure.
NSAIDs should be used cautiously in animals with pre-existing kidney disease and other conditions that cause reduced blood flow to the kidneys, like dehydration and shock. If an NSAID is used around the time of surgery, intravenous (IV) fluids are generally recommended before, during, and after anesthesia to maintain blood flow to the kidneys, hopefully reducing potential kidney complications.
The side effects of nonsteroidal anti-inflammatory drugs on the liver can be divided into two categories: (1) dose-dependent toxicity; and (2) dose-independent toxicity.
As the name implies, dose-dependent liver toxicity is related to the dose—the higher the dose of the NSAID, the worse the liver damage. Dose-dependent liver toxicity is typically caused by a massive NSAID overdose, such as a dog eating an entire bottle of his owner’s ibuprofen. (The ASPCA Animal Poison Control Center receives hundreds of calls each year involving dogs and cats that accidentally eat nonsteroidal anti-inflammatory drugs.)
Dose-independent liver toxicity can occur at any dose, even the correct one, and is an idiosyncratic reaction, meaning the patient’s liver has an abnormal sensitivity to the NSAID.
NSAIDs should be used cautiously in animals with pre-existing liver disease. For a dog starting long-term NSAID therapy for osteoarthritis, it’s good to closely monitor his or her bloodwork during the early stages because most NSAID-associated liver damage occurs within the first three weeks.
FDA-Approved NSAIDs for Pets
FDA has approved several nonsteroidal anti-inflammatory drugs for dogs to control pain and inflammation associated with osteoarthritis; and to control pain and inflammation after soft tissue and orthopedic surgery. [Orthopedic pertains to bones and muscles; soft tissue is everything else. Repairing a dog’s torn ACL (anterior cruciate ligament) in her knee is an orthopedic surgery; removing a ball from a dog’s stomach is a soft tissue surgery.]
Table 1: Some FDA-Approved Nonsteroidal Anti-Inflammatory Drugs for Dogs
|Active Ingredient||Brand Names|
|Carprofen||RIMADYL, NOVOCOX, VETPROFEN, CARPRIEVE|
|Meloxicam||METACAM, LOXICOM, OROCAM|
Most NSAIDs for dogs are given either by mouth (oral) or by injection. OROCAM is an oral spray that’s absorbed through the lining of the dog’s cheek.
Only two nonsteroidal anti-inflammatory drugs are FDA-approved for cats: METACAM (meloxicam) and ONSIOR (robenacoxib). Currently, no NSAIDs are approved for long-term use in cats due to safety concerns. Cats have a reduced ability to break down NSAIDs and are more sensitive to the drugs’ side effects.
METACAM is approved for cats as a one-time-only injection to control pain and inflammation after spaying, neutering, and orthopedic surgery; the injection is given under the cat’s skin before surgery. (The declaw procedure is the most common orthopedic surgery in cats.) Repeated use of METACAM in cats is associated with sudden-onset kidney failure and death.
ONSIOR is also approved for cats to control pain and inflammation after spaying, neutering, and orthopedic surgery; the tablets are given by mouth for no more than three days.
All FDA-approved NSAIDs for dogs and cats are prescription only.
An unapproved animal drug, such as an unapproved NSAID for pets, has not been reviewed by FDA and may not meet the agency’s strict standards for safety and effectiveness. It also may not be properly manufactured or labeled.
A main benefit of an FDA-approved nonsteroidal anti-inflammatory drug for dogs or cats is that it has been shown to be safe and effective in that species when used according to the label. Pain relievers for people don’t have the same assurances of safety and effectiveness in pets.
A second main benefit is that the label for an FDA-approved NSAID for dogs or cats is written specifically for that species. The label includes all the information veterinarians need to use the drug safely and effectively in that species.
A Balancing Act—Benefits versus Risks
FDA-approved nonsteroidal anti-inflammatory drugs offer pain relief and improved quality of life for many dogs with osteoarthritis. These drugs also help veterinarians effectively manage pain after surgery in both dogs and cats. Yet, there are risks.
NSAIDs account for the largest number of adverse drug events reported to FDA’s Center for Veterinary Medicine. Adverse drug events are undesired side effects associated with a drug or a lack of effect (the drug doesn’t do what it’s supposed to do).
If you consider the two most common populations of pets that receive NSAIDs, you can see why there are so many adverse drug events:
- Dogs with osteoarthritis. These dogs are usually geriatric and often have another disease in addition to osteoarthritis, such as pre-existing kidney or liver disease.
- Postoperative patients. These dogs and cats were recently under anesthesia which reduces blood flow to the kidneys.
All drugs have inherent risks. FDA’s Center for Veterinary Medicine tries to reduce the risks associated with NSAIDs by working with drug companies to write clear, thorough drug labels for veterinarians and client information sheets for owners.
Every oral NSAID approved for dogs and cats has an accompanying client information sheet for veterinarians to give owners each time the prescription is filled or refilled. This sheet summarizes important safety information about the drug and serves as an easy reference for you at home.
The label of every injectable NSAID has a section called “Information for Dog Owners” or “Information for Cat Owners.” Before using the drug in your pet, your veterinarian should discuss the information in this section with you.
Over-the-Counter Pain Relievers for People—Are They Safe for Pets?
Dogs are Not Small People.
Tinker Bell’s owner isn’t alone. When owners see their dog or cat limping or showing other signs of pain, they often think about giving their pet an over-the-counter pain reliever for people. But even if data show an NSAID is safe and effective in people, the drug may not be safe and effective in dogs because the drug may:
- Last longer;
- Have a higher absorption rate in the stomach and small intestine; and
- Reach higher blood levels.
These differences may lead to toxic effects in pets, such as gastrointestinal upset, ulcers, and perforations as well as liver and kidney damage.
Cats are Not Small People or Small Dogs.
You have to be even more careful with cats. Compared to other species, cats have a reduced ability to break down NSAIDs.
Table 2: Common Over-the-Counter Pain Relievers for People
|Active Ingredient||Some Common Brand Names|
|Aspirin||ASCRIPTIN, BAYER, BUFFERIN, ECOTRIN|
|Naproxen sodium||ALEVE, MIDOL EXTENDED RELIEF, NAPROSYN|
|Acetaminophen (not an NSAID)||TYLENOL|
Acetaminophen is not a nonsteroidal anti-inflammatory drug and doesn’t have much anti-inflammatory activity.Scientists don’t fully understand how acetaminophen works . The drug seems to have more than one mode of action to reduce fever and relieve pain.
Acetaminophen has two main forms of toxicity :
- Dose-dependent liver toxicity—meaning the higher the dose, the worse the liver damage—that may lead to liver failure; and
- Red blood cell damage that causes these cells to lose their ability to carry oxygen.
Dogs and cats can develop both forms of acetaminophen toxicity, but cats are more prone to red blood cell damage while dogs are more likely to get liver damage.
Cats should never be given acetaminophen. They lack certain enzymes that the liver needs to safely break down the drug.
What Should You Do?
- Before giving any NSAID to your dog or cat, talk with your veterinarian. Tell him or her if your pet:
- Has a history of gastrointestinal problems, such as stomach or intestinal ulcers, or has had surgery on the stomach or intestines. Even if your pet hasn’t had any gastrointestinal problems in the past, that doesn’t mean he or she has a healthy digestive tract. Dogs and cats can have stomach and intestinal ulcers without showing signs.
- Is on any other medication. It’s not recommended to give two different NSAIDs, or an NSAID and a steroid, at the same time.
- During and after NSAID therapy, monitor your pet for side effects, such as vomiting, diarrhea, bloody or tar-colored stool, decreased appetite, decreased activity level, yellowing of the whites of the eyes, and yellowing of the gums. These signs can occur even in a previously healthy pet. If you notice any side effects, stop giving the drug and call your veterinarian.
- If your pet experiences side effects from an NSAID, FDA’s Center for Veterinary Medicine encourages you to work with your veterinarian to submit an Adverse Drug Event report, also called an Adverse Drug Experience report.
- Before starting your dog on long-term NSAID therapy, ask your veterinarian about performing baseline bloodwork. Talk to your veterinarian about how often to recheck your dog’s bloodwork. No NSAID is currently FDA-approved for long-term use in cats.
- Going back to Tinker Bell, you shouldn’t give her anything in your medicine cabinet until you talk to your veterinarian.
Resources for You
- Veterinary Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
- Treating Pain in Your Dog – Keeping Your Best Friend Active, Safe, And Pain Free
- Currently Approved Labels for Companion Animal Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
- FDA Basics Webinar on Advice to Dog Owners Whose Pets Take NSAIDS
- FDA Basics: Is it safe for me to give my pet pain relief products approved for use in humans such as aspirin, ibuprofen, or naproxen sodium?
- Medications for your Pet…Questions for Your Vet
- Pain Medicines for Pets: Know the Risks
- Khan SA, McLean MK. Toxicology of frequently encountered nonsteroidal anti-inflammatory drugs in dogs and cats. Vet Clin North Am Small Anim Pract 2012;42:289-306.
- KuKanich B, Bidgood T, Knesl O. Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs. Vet Anaesth and Analg 2012;39:69-90.
- Lascelles BD, McFarland JM, Swann H. Guidelines for safe and effective use of NSAIDs in dogs. Vet Ther2005;6:237-251.
- Meadows I, Gwaltney-Brant S. The 10 most common toxicoses in dogs. Vet Med 2006;101:142-148.
- Plunkett SJ. Emergency Procedures for the Small Animal Veterinarian. 2nd ed. London: WB Saunders, 2001.