December 22, 2003

Dear Doctor;

At Novartis Animal Health, we are committed to providing you with the knowledge you need to prescribe our products with confidence. We are sending this letter with confidence. We are sending this letter to share new information about Deramaxx® (deracoxib), our coxib-class nonsteroid anti-inflammatory drug (NSAID)*

Since its introduction in August 2002, Deramaxx has been used safely and effectively in hundreds of thousands of dogs and more than 15 million tablets have been dispensed. (1). As is often the case when a drug begins to be used widely in a clinical setting, new information and insights about Deramaxx have come to light. With guidance from the Food and Drug Administration, Center for Veterinary Medicine (FDA/CVM), we have updated the package insert to include a section reporting post-approval adverse events. In addition, this letter includes important guidelines that may help minimize future adverse events.

As a matter of policy, Novartis Animal Health submits all adverse event reports from practicing veterinarians and consumers to the Food and Drug Administration, Center for Veterinary Medicine (FDA/CVM), including observations which are later determined to be unrelated to administration of our products. In addition, FDA/CVM receives reports directly from veterinarians and consumers. Based on the findings, a new label statement has been approved for Deramaxx incorporating post-approval experiences with the medication. The updated section of the Deramaxx label reads:

Post-Approval Experience:

The following adverse reactions are based on voluntary post-approval reporting. The categories are listed in decreasing order of frequency by body system.
· Gastrointestinal: vomiting, anorexia, diarrhea, melena, hematemesis, hematochezia, weight loss, nausea, gastrointestinal ulceration, gastrointestinal perforation, salivation.
· Hematological: anemia, thrombocytopenia.
· Hepatic: hepatic enzyme elevations, decreased or increased total protein and globulin, decreased albumin, decreased BUN, icterus, ascites, pancreatitis.
· Neurological/Behavioral/Special Sense: lethargy, weakness, seizure, ataxia, aggression, tremor, glazed eyes, uveitis, mydriasis, nystagmus.
· Urinary: azotemia, polydipsia, polyuria, urinary tract infection, hematuria, urinary incontinence, renal failure.
· Cardiovascular/Respiratory: tachypnea, bradycardia, coughing
· Dermatological/Immunological: fever, facial/muzzle edema, pruritis, urticaria, moist dermatitis.

In rare situations, death has been reported as an outcome of the adverse reactions listed above.

Warnings

The following information has also been moved from the Precautions section to the Warnings section of the veterinary label to highlight the importance of careful patient selection:

Sensitivity to drug-associated adverse events varies with the individual patient. As a class, cyclooxygenase inhibitor NSAIDs maybe associated with gastrointestinal and renal toxicity. Patients at greatest risk for NSAID toxity are those that are dehydrated, on concomitant diuretic therapy, or those with existing renal, cardiovascular and/or hepatic dysfunction. Since may NSAIDs possess the potential to produce gastrointestinal ulceration, concomitant us of DERAMAXX tablets with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided or closely monitored.

It should be noted that many of the side effects associated with Deramaxx administration occurred in cases in which dogs were also receiving corticosteroids or other NSAIDs. As stated on our original label—and that of all veterinary-approved NSAIDS—concomitant use of multiple anti-inflammatory drugs, such as NSAIDS or corticosteroids, should be avoided or closely monitored. It is important to thoroughly review a patient’s medical and therapeutic history when starting therapy with any NSAID, including Deramaxx.

Dosage and Administration

In addition, it is important to note that a significant number of the adverse reactions reported with Deramaxx were associated with inappropriate dosing of the medication. The approved dose for controlling pain and inflammation associated with orthopedic surgery is 3-4 mg/kg/day as a single daily dose, as needed, not to exceed 7 days. For control of pain and inflammation associat4ed with osteoarthritis, the approved dose is 1-2 mg/kg/day as a single daily dose as needed.

Recommended Guidelines for Deramaxx Use

In summary, the safe and effective use of our products is a primary goal at Novartis Animal Health. Guidelines we recommend to veterinarians include:
1) Examine all dogs before prescribing any medication, including Deramaxx
2) Conduct appropriate laboratory tests in dogs that may be at risk including:
a. senior pets
b. pets with history of liver disease, inflammatory bowel disease, renal disease or any other chronic condition.
3) Evaluate potential drug interactions in dogs being treated with concurrent
medications, especially steroids or other NSAIDs.
4) Observe appropriate washout periods when switching from one NSAID to another or when following corticosteroid use with NSAID therapy. The length of the washout period will vary, depending upon the patient’s condition and other drugs involved.
5) Establish baselines and periodically monitor hematology and serum biochemical data in long term patients.
6) Provide pet owners with the Deramaxx Owner Information sheet included with each Deramaxx product shipment and share all potential benefits and possible side effects with them before sending them home with Deramaxx. (Note: Veterinarians can order updated veterinary inserts and updated client information sheets free of charge at any time by calling 1-877-PET-LIT-1 and requesting item number DER 030041B for the revised veterinary insert or item number DER020046B for the revised client information sheet.)
7) Advise pet owners to watch for early signs of drug intolerance including vomiting, diarrhea and lack of appetite, and if they see the signs, discontinue use immediately and contact you.

We trust you will find this information on Deramaxx useful as you continue to expand your knowledge and experience in pain and arthritis management. Please share this letter with associates in your practice, and contact Novartis Professional Services at if you have questions about Deramaxx or any other Novartis product.

Sincerely,

(1) Data on File, Novartis Animal Health US, Inc.
* NADA #141-203 Approved by FDA