VIMOVO, a combination of naproxen and esomeprazole magnesium, is indicated in adult and adolescent
patients 12 years of age and older weighing at least 38 kg, requiring naproxen for symptomatic relief of
arthritis and esomeprazole magnesium to decrease the risk for developing naproxen-associated gastric
ulcers.

• The naproxen component of VIMOVO is indicated for relief of signs and symptoms of:

• osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in adults
• juvenile idiopathic arthritis (JIA) in adolescent patients

• The esomeprazole magnesium component of VIMOVO is indicated to decrease the risk of developing naproxen-associated gastric ulcers

VIMOVO is not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products.

Do not substitute VIMOVO with the single-ingredient products of naproxen and esomeprazole magnesium.

Controlled studies do not extend beyond 6 months.

VIMOVO does not allow for administration of a lower daily dose of esomeprazole. If a dose of esomeprazole lower than a total daily dose of 40 mg is more appropriate, a different treatment should be considered.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular  thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDS.

VIMOVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

Avoid the use of VIMOVO in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure.

Avoid the use of VIMOVO in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events.

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 events. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events.

NSAIDs, including VIMOVO, may increase the risk of bleeding events. Comorbid conditions such as coagulation disorders or concomitant use of warfarin and other anticoagulants, antiplatelet agents (e.g., aspirin), and serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase the risk.

Strategies to Minimize the GI Risks in NSAID-treated patients:

• Use the lowest effective dosage for the shortest possible duration
• Avoid administration of more than one NSAID at a time
• Avoid use in patients at higher risk unless benefits are expected to outweigh the increased
  risk of bleeding. For such as patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs
• Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
• If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue VIMOVO until a serious GI adverse event is ruled out
• In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.

Acute interstitial nephritis has been observed in patients taking PPIs including VIMOVO.

Naproxen-containing products are not recommended for use in patients with moderate to severe or severe renal impairment (creatinine clearance <30 mL/min).

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion.

VIMOVO should be avoided in patients with severe hepatic impairment.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy.

In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure.

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo-or achlorhydria.

NSAIDs, including VIMOVO, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazides diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.

NSAIDs, including naproxen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as VIMOVO. Some of these events have been fatal or life-threatening.

Published observational studies suggest that proton pump inhibitor (PPI) therapy like VIMOVO may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients.

Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). 

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including esomeprazole. 

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures.

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment.

Fluid retention and edema have been observed in some patients treated with NSAIDs. Use of naproxen may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, VIMOVO is contraindicated in patients with this form of aspirin sensitivity.

VIMOVO is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to naproxen, esomeprazole magnesium, substituted benzimidazoles, or to any components of the drug product, including omeprazole. Hypersensitivity reactions to esomeprazole may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria

• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients

• In the setting of coronary artery bypass graft (CABG) surgery

• Proton pump inhibitors (PPIs), including esomeprazole magnesium, are contraindicated in patients receiving rilpivirine-containing product

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Providers should temporarily stop esomeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high.

Avoid use of VIMOVO with St. John’s Wort or rifampin. 

Avoid concomitant use of esomeprazole with clopidogrel.

Avoid concomitant use of VIMOVO with Nelfinavir.

Avoid concomitant use with Rilpivirine-containing products.

Avoid concomitant use with Voriconazole.

The concomitant use of VIMOVO with other NSAIDs or salicylates is not recommended.

Concomitant use of VIMOVO and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity.

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities.

Naproxen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of naproxen and anticoagulants have increased the risk of serious bleeding compared to the use of either drug alone.

Increased INR and prothrombin time in patients treated with PPIs, including esomeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Monitor patients with concomitant use of VIMOVO with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as naproxen, increases the risk of serious gastrointestinal (GI) events.

NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).

Increased exposure of cilostazol when co-administered with omeprazole magnesium.

NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance.Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with esomeprazole magnesium may increase toxicity.

The concomitant use of naproxen with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

NSAIDs have produced elevations of plasma lithium levels and reductions in renal lithium clearance.

Concomitant use of esomeprazole magnesium and tacrolimus may increase exposure of tacrolimus.

Concomitant use of naproxen and cyclosporine may increase cyclosporine nephrotoxicity.

Use VIMOVO with caution in transplant patients receiving MMF.

Increased exposure of diazepam when used with VIMOVO.

Decreased exposure of esomeprazole when used concomitantly with strong inducers.

NSAIDs are associated with reversible infertility. Consider withdrawal of VIMOVO in women who have difficulties conceiving.

Use of NSAIDs during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs in pregnant women starting at 30 weeks gestation.

Esomeprazole is the S-isomer of omeprazole and limited data from published literature suggest omeprazole may be present in human milk.

GoToSource

• Pain and inflammation in patients after bilateral third molar extractions. GoToSource

• Acute gout. GoToSource

• Use in patients under the age of 12. GoToSource

⚠️  Increased drug concentration in patients with CYP2C19 gene variation.

Acute interstitial nephritis (kidney disorder) and kidney failure. GoToSource

Erosive gastritis, dyspepsia, gastric ulcer, erosive duodenitis, duodenal ulcer, erosive esophagitis, bronchitis, urinary tract infection, sinusitis, exacerbation of ulcerative colitis and crohn’s disease, birth defects, jaundice, fatal fulminant hepatitis, liver necrosis and liver failure, anemia, aspirin-sensitive asthma with severe bronchospasm, which can be fatal, osteoporosis-related fractures of the hip, wrist, or spine, blurred vision, hypomagnesemia (low serum magnesium levels), respiratory depression, conjunctivitis (inflammation of the conjunctiva), vitamin B12 deficiency, glycosuria (excess of sugar in the urine), hyperuricemia (high level of uric acid in the blood), hyponatremia (low sodium level in the blood), increased alkaline phosphatase, pneumonia, tinnitus (ringing or buzzing in the ears), hearing disturbances, pancreatitis (inflammation of the pancreas) and gait disturbance. GoToSource

Infection and clostridium difficile (colon infection causing diarrhea). GoToSource 

Rebound acid hypersecretion. GoToSource

Angioedema (rapid swelling) anaphylactic reaction/shock, myocardial infarction, stroke, new hypertension or worsening of pre-existing hypertension, inflammation, bleeding, ulceration and perforation of the stomach, small intestine, or large intestine, exfoliative dermatitis (scaling of the skin), stevens-johnson syndrome (life-threatening skin condition), toxic epidermal necrolysis (life-threatening skin condition) and inhibition of platelet aggregation leading to prolonged bleeding time. GoToSource

Cardiovascular thrombotic events, heart failure and edema (swelling caused by excess fluid). GoToSource

Subacute cutaneous lupus erythematosus (skin lesions). GoToSource

Lawsuits filed for bone fractures, infections, kidney failure, clostridium difficile, heart attacks and strokes.