•VIMOVO is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery. (4, 5.1)

Gastrointestinal Risk

•NSAIDs, including naproxen, a component of VIMOVO, 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 (GI) events. (5.4)
RECENT MAJOR CHANGES

•Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery ( 4, 5.1)

•Late pregnancy ( 4, 5.10, 8.1)

WARNINGS AND PRECAUTIONS

•Congestive heart failure and edema. VIMOVO should be used with caution in patients with fluid retention or heart failure (5.3)

•Serious gastrointestinal (GI) adverse events, which can be fatal. The risk is greater in patients with a prior history of ulcer disease or GI bleeding, and in patients at high risk for GI events, especially the elderly. VIMOVO should be used with caution in these patients ( 5.4, 8.5)

•Symptomatic response to esomeprazole does not preclude the presence of gastric malignancy ( 5.4)

•Atrophic gastritis has been noted on biopsy with long-term omeprazole therapy (5.4)

•Treatment should be withdrawn when active and clinically significant bleeding from any source occurs (5.5)

•Renal papillary necrosis and other renal injury with long-term use. Use VIMOVO with caution in the elderly, those with impaired renal function, hypovolemia, salt depletion, heart failure, liver dysfunction, and those taking diuretics, or ACE-inhibitors. Not recommended for patients with moderate or severe renal impairment ( 2, 5.6, 5.7, 7.1, 7.6, 8.7)

•Anaphylactic reactions. Do not use VIMOVO in patients with the aspirin triad (5.8)

•Serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal and can occur without warning. Discontinue VIMOVO at first appearance of skin rash or any other sign of hypersensitivity (5.9)

•Elevated liver enzymes and, rarely, severe hepatic reactions. Discontinue use immediately if abnormal liver enzymes persist or worsen ( 5.11, 8.6, 12.3)

•Should be avoided in patients with severe hepatic impairment (e.g., Child-Pugh C) ( 2, 5.11, 8.6, 12.3)

•PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. (5.16)

•Avoid concomitant use of esomeprazole with clopidogrel (5.17)

•Long-term and multiple daily dose PPI therapy is associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine (5.18)

•Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia, enterochromaffin-like cell hyperplasia, and increased Chromogranin A levels which may interfere with diagnostic investigations for neuroendocrine tumors. (5.20)

•Hypomagnesemia has been reported rarely with prolonged treatment with PPIs (5.21)

•Avoid concomitant use of VIMOVO with St John’s Wort or rifampin due to the potential reduction in esomeprazole levels. ( 5.22, 7.16)

•Concomitant use of NSAIDs increases lithium plasma levels (7.7)

•Methotrexate: VIMOVO may increase serum levels of methotrexate (7.8)

•Concomitant use of VIMOVO with warfarin may result in increased risk of bleeding complications. Monitor for increases in INR and prothrombin time (7.9)

•Esomeprazole inhibits gastric acid secretion and may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts, erlotinib and digoxin). Patients treated with VIMOVO and digoxin may need to be monitored for increases in digoxin toxicity (7.14)

•Clopidogrel: esomeprazole, a component of VIMOVO, decreases exposure to the active metabolite of clopidogrel. ( 7.16, 12.3)

•Renal Insufficiency: VIMOVO is not recommended in patients with moderate or severe renal insufficiency (2, 5.6, 5.7, 8.7, 12.3)

Revised: 10/2012