The table below lists all adverse reactions, regardless of causality, occurring in >2% of patients from 2 clinical studies conducted in patients with osteoarthritis of the knee (Study 3 and Study 4).

Table 2: Adverse Reactions occurring in patients >2% (Study 3 and Study 4) Preferred term (sorted by SOC)
 VIMOVO 500 mg/20 mg twice daily

(n=490)

%
 Placebo

(n=246)

%
 
Gastrointestinal Disorders
 
 
 
Dyspepsia
 8
 12
 
Diarrhea
 6
 4
 
Abdominal Pain Upper
 4
 3
 
Constipation
 4
 1
 
Nausea
 4
 4
 
Nervous System Disorders
 
 
 
Dizziness
 3
 2
 
Headache
 3
 5
 
General disorders and administration site conditions
 
 
 
Peripheral edema
 3
 1
 
Respiratory, thoracic and mediastinal disorders
 
 
 
Cough
 1
 3
 
Infections and infestations
 
 
 
Sinusitis
 1
 2
 

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 eva luated 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.

6.2 Postmarketing Experience
Naproxen

The following adverse reactions have been identified during post-approval use of naproxen. 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. These reports are listed below by body system:

Body as a Whole: anaphylactoid reactions, angioneurotic edema, menstrual disorders, pyrexia (chills and fever)

Cardiovascular: congestive heart failure, vasculitis, hypertension, pulmonary edema

Gastrointestinal: gastrointestinal bleeding and/or perforation, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn’s disease), nonpeptic gastrointestinal ulceration, ulcerative stomatitis, esophagitis, peptic ulceration

Hepatobiliary: jaundice, abnormal liver function tests, hepatitis (some cases have been fatal)

Hemic and Lymphatic: eosinophilia, leukopenia, melena, thrombocytopenia, agranulocytosis, granulocytopenia, hemolytic anemia, aplastic anemia

Metabolic and Nutritional: hyperglycemia, hypoglycemia

Nervous System: inability to concentrate, depression, dream abnormalities, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis, cognitive dysfunction, convulsions

Respiratory: eosinophilic pneumonitis, asthma

Dermatologic: alopecia, urticaria, skin rashes, toxic epidermal necrolysis, erythema multiforme, ery