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The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS]
- GI Bleeding, Ulceration and Perforations [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
- Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS]
- Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
- Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
- Hematologic Toxicity [see WARNINGS AND PRECAUTIONS]
- Active Bleeding [see WARNINGS AND PRECAUTIONS]
- Acute Interstitial Nephritis [see WARNINGS AND PRECAUTIONS]
- Cyanocobalamin (vitamin B-12) Deficiency [see WARNINGS AND PRECAUTIONS]
- Clostridium difficile Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
- Bone Fracture [see WARNINGS AND PRECAUTIONS]
- Hypomagnesemia [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Clinical Trials Experience With VIMOVO
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The adverse reactions reported below are specific to the clinical trials with VIMOVO.
The safety of VIMOVO was evaluated in clinical studies involving 2317 patients (aged 27 to 90 years) and ranging from 3 to 12 months. Patients received either 500 mg/20 mg of VIMOVO twice daily (n=1157), 500 mg of enteric-coated naproxen twice daily (n=426), or placebo (n=246). The average number of VIMOVO doses taken over 12 months was 696+44.
The table below lists all adverse reactions, regardless of causality, occurring in > 2% of patients receiving VIMOVO and higher in the VIMOVO group than control from two clinical studies (Study 1 and Study 2). Both of these studies were randomized, multi-center, double-blind, parallel studies. The majority of patients were female (67%), white (86%). The majority of patients were 50-69 years of age (83%). Approximately one quarter were on low-dose aspirin.
Table 1: Adverse Reactions* in Study 1 and Study 2 (endoscopic
|Preferred term||VIMOVO 500mg/20 mg twice daily
|EC-Naproxen 500 mg twice daily
|Upper respiratory tract infection||5||4|
|Urinary tract infection||2||1|
|*reported in > 2% of patients and higher in the VIMOVO group than control|
In Study 1 and Study 2, patients taking VIMOVO had fewer premature discontinuations due to adverse reactions compared to patients taking enteric-coated naproxen alone (7.9% vs. 12.5% respectively). The most common reasons for discontinuations due to adverse events in the VIMOVO treatment group were upper abdominal pain (1.2%, n=5), duodenal ulcer (0.7%, n=3) and erosive gastritis (0.7%, n=3). Among patients receiving enteric-coated naproxen, the most common reasons for discontinuations due to adverse events were duodenal ulcer 5.4% (n=23), dyspepsia 2.8% (n=12) and upper abdominal pain 1.2% (n=5). The proportion of patients discontinuing treatment due to any upper gastrointestinal adverse events (including duodenal ulcers) in patients treated with VIMOVO was 4% compared to 12% for patients taking entericcoated naproxen.
The table below lists all adverse reactions, regardless of causality, occurring in > 2% of patients and higher in the VIMOVO group than placebo from 2 clinical studies conducted in patients with osteoarthritis of the knee (Study 3 and Study 4).
Table 2: Adverse Reactions*
in Study 3 and Study 4
|Preferred term||VIMOVO 500 mg/20 mg twice daily
|Abdominal Pain Upper||4||3|
|*reported in > 2% of patients and higher in the VIMOVO group than placebo|
The percentage of subjects who withdrew from the VIMOVO treatment group in these studies due to treatment-emergent adverse events was 7%. There were no preferred terms in which more than 1% of subjects withdrew from any treatment group.
The long-term safety of VIMOVO was evaluated in an open-label clinical trial of 239 patients, of which 135 patients received 500 mg/20 mg of VIMOVO for 12 months. There were no differences in frequency or types of adverse reactions seen in the long-term safety study compared to shorter-term treatment in the randomized controlled studies.
Clinical Trials Experience With Naproxen And Other NSAIDs
In patients taking naproxen in clinical trials, the most frequent reported adverse experiences in approximately 1% to 10% of patients are:
Gastrointestinal: heartburn, nausea, dyspepsia, stomatitis
Special Senses: tinnitus, visual disturbances, hearing disturbances
General: dyspnea, thirst
In patients taking NSAIDs, the following adverse experiences have also been reported in approximately 1% to 10% of patients.
Gastrointestinal: gross bleeding/perforation, GI ulcers (gastric/duodenal), vomiting
General: abnormal renal function, anemia, elevated liver enzymes, increased bleeding time, rashes
The following are additional adverse experiences reported in < 1% of patients taking naproxen during clinical trials.
Nervous System: inability to concentrate
Dermatologic: skin rashes
In patients taking NSAIDs, the following adverse experiences have also been reported in < 1% of patients.
Body as a Whole: fever, infection, sepsis, anaphylactic reactions, appetite changes, death
Hepatobiliary: hepatitis, liver failure
Metabolic and Nutritional: weight changes
Dermatologic: exfoliative dermatitis
Special Senses: blurred vision, conjunctivitis
Clinical Trials Experience With Esomeprazole Magnesium
Additional adverse reactions that were reported as possibly or probably related to NEXIUM with an incidence of < 1% are listed below by body system:
Body as a Whole: abdomen enlarged, allergic reaction, asthenia, back pain, chest pain, substernal chest pain, facial edema, hot flushes, fatigue, fever, flu-like disorder, generalized edema, malaise, pain, rigors
Cardiovascular: flushing, hypertension, tachycardia
Gastrointestinal: dyspepsia, dysphagia, dysplasia GI, epigastric pain, eructation, esophageal disorder, gastroenteritis, GI hemorrhage, GI symptoms not otherwise specified, hiccup, melena, mouth disorder, pharynx disorder, rectal disorder, serum gastrin increased, tongue disorder, tongue edema, ulcerative stomatitis, vomiting
Hearing: earache, tinnitus
Nervous System/Psychiatric: anorexia, apathy, appetite increased, confusion, depression aggravated, hypertonia, nervousness, hypoesthesia, impotence, insomnia, migraine, migraine aggravated, paresthesia, sleep disorder, somnolence, tremor, vertigo, visual field defect
Reproductive: dysmenorrhea, menstrual disorder, vaginitis
Special Senses: otitis media, parosmia, taste loss
Visual: conjunctivitis, vision abnormal
The following potentially clinically significant laboratory changes in clinical trials, irrespective of relationship to esomeprazole, were reported in ≤ 1% of patients: increased creatinine, uric acid, total bilirubin, alkaline phosphatase, ALT, AST, hemoglobin, white blood cell count, platelets, serum gastrin, potassium, sodium, thyroxine and thyroid stimulating hormone. Decreases were seen in hemoglobin, white blood cell count, platelets, potassium, sodium, and thyroxine.
Endoscopic findings that were reported as adverse reactions include: duodenitis, esophagitis, esophageal stricture, esophageal ulceration, esophageal varices, gastric ulcer, hernia, benign polyps or nodules, Barrett's esophagus, and mucosal discoloration.
The following adverse reactions have been identified during post-approval use of VIMOVO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: gait disturbance
Injury, Poisoning and Procedural Complications: contusion, fall
Musculoskeletal and Connective Tissue: joint swelling, muscle spasms
Urogenital: renal tubular necrosis
Body as a Whole: angioneurotic edema, menstrual disorders
Gastrointestinal: inflammation, bleeding (sometimes fatal, particularly in the elderly), ulceration, and obstruction of the upper or lower gastrointestinal tract, esophagitis, stomatitis, hematemesis, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease)
Hepatobiliary: hepatitis (some cases have been fatal)
Nervous System: depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions
Respiratory: eosinophilic pneumonitis
Dermatologic: alopecia, urticaria, toxic epidermal necrolysis, erythema multiforme, erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, systemic lupus erythematoses, bullous reactions, including Stevens-Johnson syndrome, photosensitive dermatitis, photosensitivity reactions, including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa. If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.
Special Senses: hearing impairment, corneal opacity, papillitis, retrobulbar optic neuritis, papilledema
Urogenital: glomerular nephritis, hematuria, hyperkalemia, interstitial nephritis, nephrotic syndrome, renal disease, renal failure, renal papillary necrosis, raised serum creatinine
Reproduction (female): infertility
Blood and Lymphatic: agranulocytosis
Eye: blurred vision
Gastrointestinal: pancreatitis, microscopic colitis
Hepatobiliary: hepatic failure, hepatitis with or without jaundice
Immune System: anaphylactic reaction/shock
Infections and Infestations: GI candidiasis, Clostridium difficile associated diarrhea
Musculoskeletal and Connective Tissue: muscular weakness, myalgia, bone fracture
Nervous System: hepatic encephalopathy
Psychiatric: aggression, agitation, hallucination
Renal and Urinary: interstitial nephritis
Reproductive System and Breast: gynecomastia
Respiratory, Thoracic, and Mediastinal: bronchospasm
Skin and Subcutaneous Tissue: alopecia, erythema multiforme, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis (some fatal)
Read the Vimovo (naproxen and esomeprazole magnesium delayed release tablets) Side Effects Center for a complete guide to possible side effects
See Table 3 and Table 4 for clinically significant drug interactions and interactions with diagnostics with naproxen and esomeprazole.
Table 3: Clinically Significant Drug Interactions with
Naproxen and Esomeprazole – Affecting Drugs Co-Administered with VIMOVO and
Interactions with Diagnostics
|Drugs That Interfere with Hemostatis|
|Intervention:||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 [see WARNINGS AND PRECAUTIONS].
Clopidoarel: Avoid concomitant use of clopidogrel with VIMOVO. Consider use of alternative anti-platelet therapy [see WARNINGS AND PRECAUTIONS].
|Clinical Impact:||Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS].|
|Intervention:||Concomitant use of VIMOVO and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS].
Vimovo is not a substitute for low dose asprin for cardiovascular protection.
|ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers|
|Clinical Impact:||Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriurectic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of VIMOVO with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see WARNINGS AND PRECAUTIONS].|
The effect of esomeprazole on antiretroviral drugs is variable.
|Intervention:||Atazanavir: See prescribing information for atazanavir for dosing information.
Nelfinavir: Avoid concomitant use with VIMOVO.
Saquinavir: See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities. Other antiretrovirals: See prescribing information of specific drugs.
|Clinical Impact:||Increased exposure of cilostazol and one of its active metabolities (3,4-dihydro-cilostazol) when coadministered with esomeprazole, the racemate of esomeprazole [see CLINICAL PHARMACOLOGY].|
|Intervention:||Consider reducing the dose of cilostazol to 50 mg twice daily.|
|Intervention:||Monitor digoxin concentrations during concomitant use of VIMOVO. Dose adjustment of digoxin may be needed to maintain therapeutic drug concentrations.|
|Clinical Impact:||NSAIDs have produced elevations of plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of VIMOVO and lithium, monitor patients for signs of lithium toxicity.|
|Intervention:||During concomitant use of VIMOVO and methotrexate, monitor patients for methotrexate toxicity. A temporary withdrawal of VIMOVO may be considered in some patients receiving high-dose methotrexate.|
|Clinical Impact:||Concomitant use of naproxen and cyclosporine may increase cyclosporine’s nephrotoxicity.|
|Intervention:||During concomitant use of VIMOVO and cyclosporine, monitor patients for signs of worsening renal function.|
|Clinical Impact:||Concomitant use of esomeprazole and tacrolimus may increase exposure of tacrolimus|
|Intervention:||During concomitant use of VIMOVO and tacrolimus, monitor tacrolimus whole blood concentrations.|
|NSAIDs and Salicylates|
|Clinical Impact:||Concomitant use of naproxen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see WARNINGS AND PRECAUTIONS].|
|Intervention:||The concomitant use of VIMOVO with other NSAIDs or salicylates is not recommended.|
|Clinical Impact:||Concomitant use of VIMOVO and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).|
|Intervention:||During concomitant use of VIMOVO and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity.|
|Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, mycophenoloate mofetil, ketoconazole)|
|Clinical Impact:||Esomeprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity|
|Intervention:||Mycophenolate mofetil (MMF): Co-administration of omeprazole, of which esomeprazole is an enantiomer, in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving esomeprazole and MMF. Use VIMOVO with caution in transplant patients receiving MMF [see CLINICAL PHARMACOLOGY]. See the prescribing information for other drugs dependent on gastric pH for absorption.|
|Interactions With Investigations of Neuroendocrine Tumors|
|Clinical Impact:||Serum chromogranin A (CgA) levels increase secondary to PPI-induced decreases in gastric acidity. The increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].|
|Intervention:||Temporarily stop VIMOVO treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g. for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary.|
|Clinical Impact:||Increased exposure of diazepam [see CLINICAL PHARMACOLOGY].|
|zIntervention:||Monitor patients for increased sedation and adjust the dose of diazepam as needed.|
Table 4: Clinically
Significant Interactions with Esomeprazole --Affecting Co-Administered Drugs
|CYP2C19 or CYP3A4 Inducers|
|Clinical Impact:||Decreased exposure of esomeprazole when used concomitantly with strong inducers [see CLINICAL PHARMACOLOGY].|
|Intervention:||St. John’s Wort, rifampin: Avoid concomitant use with VIMOVO [see WARNINGS AND PRECAUTIONS].|
|Clinical Impact:||Increased exposure of esomeprazole [see CLINICAL PHARMACOLOGY].|
|Intervention:||Dose adjustment of VIMOVO is not normally required.|
Read the Vimovo Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 5/24/2016
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