FDA NSAID report-Pain drugs for dogs

<center>Pain Drugs for Dogs: Be an Informed Pet Owner</center>
By Linda Bren

A decade ago, few drugs were available to treat pets in pain at home. Pups were spayed or neutered at the animal hospital, stitched up, and sent home without pain medication. And dogs with painful arthritis limped along without drugs that were safe and effective for long-term use.

Today, a new generation of nonsteroidal anti-inflammatory drugs (NSAIDs) is bringing relief to millions of dogs with joint problems or with pain after surgery.

"NSAIDs are extremely effective for controlling pain and inflammation in dogs," says Stephen F. Sundlof, D.V.M., Ph.D., director of the Food and Drug Administration's Center for Veterinary Medicine (CVM). "These are very valuable drugs that help many pets live to a ripe old age."

But like any drugs, NSAIDs carry a risk of side effects, or adverse reactions. Most adverse reactions are mild, but some may be serious, especially if the drugs are not used according to labeled directions. Some reactions result in permanent damage or even death.

"It's important for pet owners to be aware of the risks and benefits of all drugs, including NSAIDs, so that they can make informed decisions about their pets' health care," says Sundlof. "Owners who give their dog NSAIDs need to know the side effects to watch for that indicate their pet needs medical attention."

The most common side effects from NSAIDs include vomiting, loss of appetite, depression, lethargy, and diarrhea. Serious side effects include gastrointestinal bleeding, ulcers, perforations, kidney damage, and liver problems.

"The side effects of NSAIDs are very well known and very well documented," says Michele Sharkey, D.V.M., in the CVM's Office of New Animal Drug Evaluation. But this information is not always getting to the pet owner, she says. "If the pet owner can recognize a possible reaction, stop the medication, and get veterinary help, it could mean the difference between a good outcome and a disaster."

Safety and Effectiveness
The CVM, which regulates drugs for use in animals, has approved some NSAIDs for use in dogs with pain from degenerative joint disease (osteoarthritis) or with pain after surgery. These include Etogesic (etodolac), Rimadyl (carprofen), Metacam (meloxicam), Zubrin (tepoxalin), Deramaxx (deracoxib), Previcox (firocoxib), and Novox (generic carprofen).

NSAIDs help to control signs of arthritis, including inflammation, swelling, stiffness, and joint pain. Inflammation--the body's response to irritation or injury--is characterized by redness, warmth, swelling, and pain. NSAIDs work by blocking the production of prostaglandins, the body chemicals that cause inflammation.

The FDA considers approved NSAIDs to be safe and effective when used according to the label and when dog owners are informed about common NSAID adverse reactions.

And veterinarians are becoming increasingly aware of the advantages of recognizing and controlling pain, says Charles Lemme, D.V.M., a member of the American Veterinary Medical Association (AVMA), Clinical Practitioners Advisory Committee. "We recognize that pets are healing better and faster with pain control."

Lemme says that the emphasis on pain management may be partly because of the availability of the newer NSAIDs. "The NSAIDs we have available now are a lot safer than what we've had before and we're seeing far fewer side effects than before."

Before the newer generation of NSAIDs came along, "people were using NSAIDs such as aspirin in an attempt to mitigate arthritic pain," says Michael Andrews, D.V.M., president of the American Animal Hospital Association (AAHA). "We saw the consequence of their use," adds Andrews, who recalls seeing a client who gave her dog aspirin for six weeks, two times a day. "The dog had a bleeding nose that wouldn't stop."

"NSAIDs are used in many, many dogs and the frequency of problems is quite low," says Andrews. "The duration of use makes a difference in safety. If used for a day or two, the risks often are much lower than when used over long periods of time for a chronic arthritic condition."

Drugs used to control pain should be given only when necessary, and in the smallest dose that is effective, says Sharkey. "Arthritis waxes and wanes. Some animals get worse in cold weather. If the dog seems to improve to the point of not needing the drug, the owner should discuss continued use of the NSAID with a veterinarian."

An owner should never give an NSAID to a pet, or increase the dose or frequency of a drug, without the veterinarian's instructions, adds Sharkey. "Just like different people respond differently to a drug, the way each dog responds to an NSAID varies." Because of this individual response, no one NSAID is considered more effective than another, and because every NSAID can cause adverse reactions, none is considered safer than others.

If a pet is prescribed an NSAID, the CVM recommends that pet owners take the following steps to make sure they are fully informed about the drug and can make the best decision for their pet's health.

Ask Questions and Tell All
Ask your veterinarian about the benefits, risks, and side effects of any medication, including NSAIDs. "An informed dog owner is the best defense against serious side effects from NSAIDs," says Sharkey. "Owners should not hesitate to ask questions and inquire about possible side effects or signs to watch for when treating a dog."

Tell your veterinarian your pet's symptoms and current medications, including prescriptions, over-the-counter drugs, vitamins, herbal supplements, and flea control products. Giving NSAIDS and other medications together could harm your pet. Aspirin, for instance, may be in a supplement you're giving to your pet, says Sharkey, and should not be used in conjunction with an NSAID.

Ask for the Client Information Sheet
Pet owners should receive a "Client Information Sheet" with every NSAID prescription. Client Information Sheets, also called "Information for Dog Owner Sheets," are user-friendly summaries that explain the results to expect from using the drug, what to discuss with your veterinarian before giving the drug, possible side effects to look for, and other important information. The FDA has helped the pharmaceutical companies who make NSAIDs for dogs develop these sheets for the owners, and the companies provide them with each NSAID they ship.

Ask your veterinarian for the sheet if you do not receive one, and read the information carefully before giving the medication to your dog. If your veterinarian can't provide the Client Information Sheet, you can get one by printing it from the CVM's Web site or by calling the toll-free number of the drug company.

Bernadette Dunham, D.V.M., Ph.D., deputy director in the CVM's Office of New Animal Drug Evaluation, explains why some veterinarians may be unable to locate the Client Information Sheet. "They often have the role of veterinarian and the role of pharmacist," she says. Veterinary hospitals get shipments of drugs from the pharmaceutical companies or distributors. Then they may repackage the drug in their hospitals' bottles, often in smaller quantities for distributing to clients. In the repackaging process, the Client Information Sheet, which is often printed on the package insert for the veterinarian, may be tossed out inadvertently.

The FDA, the veterinary community, and the pharmaceutical companies are working together to ensure that NSAIDs are used safely and responsibly and that owners are given the Client Information Sheets.

"The pharmaceutical companies are trying to come up with creative ideas to make it easier for busy veterinarians," says Dunham. Many companies are making the Client Information Sheet a tear-off sheet that can be easily separated from the drug labeling.

Some companies also are packaging drugs in smaller quantities with the Client Information Sheet sealed inside the package. Therefore, the veterinarian can just attach the hospital label and dosing instructions on the drug container without repackaging the drug and inadvertently discarding the sheet.

Through published journal articles, electronic newsletters, and information posted on their Web sites, both the AVMA and the AAHA are reinforcing the importance of client communication regarding NSAIDs, including handing out the Client Information Sheets, to their veterinary members.

Get the Recommended Tests
NSAIDs approved for use in dogs contain the following information on their labels:

All dogs should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests to establish baseline blood values prior to, and periodically during, the use of any NSAID are strongly recommended.

If the veterinarian recommends a blood test before administering an NSAID to a dog, don't decline it, advises Sharkey. "There are good reasons for it." The knowledge gained from these tests could be critical in deciding whether the drug is safe to use in a dog.

Testing is particularly important with long-term NSAID use, such as to treat arthritic pain, says Andrews. "It makes sense to do some preliminary screening blood work and periodic tests to identify any problems and monitor how well the pet is tolerating the drug over time."

Work With Your Veterinarian to Find the Best NSAID
Many NSAID choices are available, and selecting the best NSAID for a particular pet is important, says Sharkey. "Sometimes, the process of finding the best one can mean changing the prescription."

Lynne Heslip of Howell, Mich., tried several NSAIDs on her 4-year-old Irish wolfhound, O.B., who had painful hip dysplasia. "The first NSAID did not work well," she says. "Pain relief seemed to be minimal, and she had vomiting and wasn't interested in eating." Heslip watched her normally outgoing dog seclude herself behind the kitchen table. "She was severely depressed. She didn't want to interact with other animals or with people."

Working with her veterinarian, Heslip stopped the NSAID, waited five days for the drug to clear out of the dog's system, and tried another NSAID. "Within one week, I noticed a drastic change for the better," says Heslip. "She was much more animated and happier." O.B. was on NSAIDs for about three years until her death. Heslip reports that her current 6-year-old Irish wolfhound, Isabella, is on the same NSAID, with very good results.

Bad Reaction? Stop Medication and Call a Veterinarian
If you suspect an adverse reaction to an NSAID, stop administering the drug and contact a veterinarian immediately. Some reactions are mild and go away after stopping the drug.

When giving a pet an NSAID, watch for these side effects, which are listed on the Client Information Sheet and on the drug label:

Decrease or increase in appetite
Vomiting
Change in bowel movements (such as diarrhea or black, tarry, or bloody stools)
Change in behavior (such as decreased or increased activity level, seizure, aggression, or lack of coordination)
Yellowing of gums, skin, or whites of the eyes (jaundice)
Change in drinking habits (frequency or amount consumed)
Change in urination habits (frequency, color, or smell)
Change in skin (redness, scabs, or scratching).
These side effects are the most common. But not all possible side effects are included on the Client Information Sheet or on the drug label. Always contact your veterinarian if you have questions about your dog's medication.

What starts out as a minor problem can rapidly progress to an emergency. An owner should be encouraged to call his or her veterinarian with any concerns about the NSAID the dog is receiving. You may even call the drug manufacturer's toll-free number that appears on each Client Information Sheet. When problems are experienced with a product, the manufacturer may have specific recommendations for your veterinarian regarding tests and treatments.

Cindi Brinkley of Danville, Ill., rushed her dog to the veterinarian at the first sign of a bad reaction. Maude, a cocker spaniel-collie mix, injured herself when she was 11 months old while playing with a littermate in the house. "She slipped on the basement floor coming out of a turn, and both back legs splayed out," says Brinkley.

Maude was diagnosed with a deformed hip joint and scheduled for corrective surgery. In the meantime, the veterinarian prescribed an NSAID for pain control. "I was not told a thing about the drug other than how to give it to her," says Brinkley.

Maude had been on the drug for a month when Brinkley came home from work one day to find the dog bleeding from her rectum. "It was very, very frightening," she says. "The whole back of my dog was bright red--I thought she was bleeding to death." After treatment in the veterinary hospital and discontinuation of the drug, Maude recovered from the incident. Now more than 7 years old, "she has some vomiting and loose stools every so often," says Brinkley, who suspects the digestive problems may be a lasting effect of the drug.

Report Bad Reactions
If you or your veterinarian suspects that an adverse reaction is related to the use of an NSAID or any drug, it should be reported to the pharmaceutical company. Usually, the veterinarian reports it, but if the veterinarian doesn't, the owner should. The company, by law, has to report all adverse reactions to the FDA, which looks for signals of increased frequency and severity of adverse reactions. The FDA works with the pharmaceutical firms to address these events and improve the ability of the product to be more safely used.

If unable to report problems directly to the pharmaceutical company, veterinarians and owners are encouraged to report veterinary Adverse Drug Experiences (ADEs) and suspected product failures to the government agency that regulates the product. Adverse experiences with NSAIDs should be reported to the FDA's CVM.

Michele Sharkey, D.V.M., of the FDA's Office of New Animal Drug Evaluation, contributed to this article.


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Medicate Under Veterinary Supervision
The FDA has approved some nonsteroidal anti-inflammatory drugs (NSAIDs) for use in dogs. In the United States, there are no oral NSAIDs approved for use in cats. Veterinarians can, however, legally prescribe human drugs to animals unless it presents a risk to the public health. This type of use is known as extralabel, or off-label, for uses not listed on the label. Extralabel use can also mean prescribing a drug to a different species, for a different condition, or in a different dosage than that for which the drug was approved. For example, a veterinarian may prescribe a lower dose of an NSAID drug approved for dogs to a cat with an inflamed joint.

But pet owners should not give their own drugs to pets or otherwise medicate their animals without veterinary supervision, says Michele Sharkey, D.V.M., in the FDA's Center for Veterinary Medicine.

Different species metabolize drugs differently, she says. "You take aspirin or Tylenol on any given day for a headache and not think twice about it, but dogs are more sensitive to aspirin than humans, and one Tylenol can kill a cat. Pet owners should always work with their veterinarians to make medication decisions."<table width="98%" border="1" cellpadding="5" cellspacing="0" class="data" summary="Approved nonsteroidal anti-inflammatory drugs for use in dogs, including indication for use, name of manufacturer, and type of dosage."> <tr> <th valign="middle" scope="col"> Brand name</th> <th valign="middle" scope="col"> Established name</th> <th valign="middle" scope="col"> Manufacturer/<br /> distributor and year of FDA approval</th> <th valign="middle" scope="col"> Indication</th> <th valign="middle" scope="col"> Type of dosage</th> <th valign="middle" scope="col"> Manufacturer's telephone number for assistance or to report suspected adverse reaction</th> </tr> <tr> <td align="center" valign="middle" scope="row"> Etogesic</td> <td width="14%" align="center" valign="middle"> etodolac</td> <td align="center" valign="middle"> Fort Dodge Animal Health, 1998</td> <td align="center" valign="middle"> management of pain and inflammation associated with osteoarthritis in dogs</td> <td align="center" valign="middle"> tablet</td> <td align="center" valign="middle"> (800) 533-8536</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Rimadyl</td> <td align="center" valign="middle"> carprofen</td> <td align="center" valign="middle"> Pfizer Animal Health, 1996 (caplet); 1999 (tablet); 2003 (injectable)</td> <td align="center" valign="middle"> relief of pain and inflammation associated with osteoarthritis in dogs; control of postoperative pain associated with soft tissue and orthopedic surgeries in dogs</td> <td align="center" valign="middle"> caplet and chewable tablet; injection</td> <td align="center" valign="middle"> (800) 366-5288</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Deramaxx</td> <td align="center" valign="middle"> deracoxib</td> <td align="center" valign="middle"> Novartis Animal Health US Inc., 2002</td> <td align="center" valign="middle"> control of pain and inflammation associated with osteoarthritis in dogs; control of postoperative pain and inflammation associated with orthopedic surgery in dogs 4 lbs or greater </td> <td align="center" valign="middle"> chewable tablet</td>
<td align="center" valign="middle"> (800) 332-2761</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Metacam</td> <td align="center" valign="middle"> meloxicam</td> <td align="center" valign="middle"> Boehringer Ingelheim Vetmedica Inc., 2003 (oral suspension, and injectable)</td> <td align="center" valign="middle"> control of pain and inflammation associated with osteoarthritis in dogs</td> <td align="center" valign="middle"> drops given by mouth; injection</td> <td align="center" valign="middle"> (866) METACAM (638-2226)</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Zubrin</td> <td align="center" valign="middle"> tepoxalin</td> <td align="center" valign="middle"> Schering-Plough Animal Health Corp., 2003</td> <td align="center" valign="middle"> control of pain and inflammation associated with osteoarthritis in dogs</td> <td align="center" valign="middle"> rapidly disintegrating tablet</td> <td align="center" valign="middle"> (800) 224-5318</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Previcox</td> <td align="center" valign="middle">firocoxib</td> <td align="center" valign="middle"> Merial Ltd., 2004</td> <td align="center" valign="middle"> control of pain and inflammation associated with osteoarthritis in dogs</td> <td align="center" valign="middle"> chewable tablet</td> <td align="center" valign="middle"> (877) 217-3543</td> </tr> <tr> <td align="center" valign="middle" scope="row"> Novox</td> <td align="center" valign="middle"> generic carprofen</td> <td align="center" valign="middle"> IMPAX Laboratories Inc./Vedco Inc., 2005</td> <td align="center" valign="middle"> relief of pain and inflammation associated with osteoarthritis in dogs</td> <td align="center" valign="middle"> caplet</td> <td align="center" valign="middle"> (888) 708-3326</td> </tr></table>Table by:U.S. Food and Drug Administration
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Questions regarding ADE reporting should be addressed to:
Center for Veterinary Medicine
Division of Surveillance, HFV-210
7519 Standish Place
Rockville, MD 20855
(888) FDA-VETS (332-8387)

For More Information
FDA Center for Veterinary Medicine
www.fda.gov/cvm/

American Veterinary Medical Association
www.avma.org

American Animal Hospital Association
www.aahanet.org