NonSelective NSAIDs: Diclofenac epolamine, Diclofenac potassium, Diclofenac sodium, Diflunisal, Etodolac, Fenoprofen, Flurbiprofen, Ibuprofen*, Indomethacin, Ketoprofen*, Ketorolac**, Meclofenamate, Mefenamic Acid, Meloxicam, Nabumetone, Naproxen sodium*, Oxaprozin, Oxaprozin potassium, Piroxicam, Salsalate, Sulindac, Tolmetin

Cardiovascular Risk

• NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
• These NSAIDs are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery

Gastrointestinal Risk

• NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms.
• Elderly patients are at greater risk for serious gastrointestinal events.
• Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet drugs (such as aspirin), anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.

Pediatric Use

• The safety and effectiveness of nonselective NSAIDs have been established in pediatric patients 6 years and older based on evidence from adequate and well-controlled studies with nonselective NSAIDs in adults, as well as an open-label study in pediatric patients 6 years and older. The pediatric study enrolled 104 patients, 6 years of age and older with minor soft tissue injuries. One nonselective NSAIDs was applied to the injury site twice daily for a maximum of 14 days or until treatment was no longer required for pain management, whichever occurred first. Based on the available data from the pediatric study, the safety profile of nonselective NSAIDs topical system in pediatric patients is similar to that in adults. The safety and effectiveness of nonselective NSAIDshas not been investigated in pediatric patients less than 6 years old.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as indomethacin. Some of these events have been fatal or life- threatening.   DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that       early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue indomethacin capsules and evaluate the patient immediately.

Fetal Toxicity

• Avoid use of NSAIDs in pregnant women at about 30 weeks gestation and later. NSAIDs increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestation age.

 * These products are also available in nonprescription forms

**Additional Boxed Warning for Ketorolac(Oral, Injection)