What is the use of Naproxen (Nonsteroidal Anti-Inflammatory Drug, NSAID)?

From the Guidelines

Naproxen should be used with caution, at the lowest effective dose, and for the shortest duration possible, due to its potential to increase the risk of gastrointestinal complications, cardiovascular events, and other adverse effects, as highlighted in the 2008 ACCF/ACG/AHA expert consensus document 1.

Key Considerations

• Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that works by blocking enzymes called cyclooxygenases (COX) that produce prostaglandins, chemicals involved in inflammation and pain.
• The typical adult dose is 250-500 mg taken twice daily, with a maximum daily dose of 1500 mg.
• Naproxen should be taken with food to reduce stomach irritation and should not be used long-term without medical supervision due to potential side effects.
• These side effects can include stomach ulcers, bleeding, kidney problems, and increased risk of heart attack or stroke, especially with prolonged use.

Special Populations

• People with heart disease, high blood pressure, kidney disease, or a history of stomach ulcers should use naproxen cautiously.
• Naproxen should not be combined with other NSAIDs or taken during late pregnancy.
• If you experience black stools, severe stomach pain, or difficulty breathing while taking naproxen, seek medical attention immediately.

Evidence-Based Recommendations

• The use of naproxen and other NSAIDs has been associated with an increased risk of cardiovascular events, as reported in the 2007 focused update of the ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction 1.
• A stepped-care approach to pain management should be used, starting with acetaminophen or aspirin, and naproxen may be considered if initial therapy is insufficient, as recommended in the 2007 focused update of the ACC/AHA guidelines 1.
• The risk of gastrointestinal complications with naproxen can be modified, but not eliminated, through careful use of coxibs and gastroprotective therapies, as noted in the consensus development conference on the use of nonsteroidal anti-inflammatory agents 1.

From the FDA Drug Label

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events 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, myocardial infarction, and stroke, which can be fatal.

Patients with known CV disease or risk factors for CV disease may be at greater risk.

To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible.

The FDA drug label warns of an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, associated with the use of naproxen.

• Patients with known CV disease or risk factors for CV disease may be at greater risk.
• To minimize the potential risk, the lowest effective dose should be used for the shortest duration possible 2.
• Naproxen should be used with caution in patients with hypertension, and blood pressure should be monitored closely during treatment 2.
• The use of naproxen may lead to fluid retention, edema, and peripheral edema, and should be used with caution in patients with fluid retention, hypertension, or heart failure 2.

From the Research

Naproxen Overview

• Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that is effective in alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis 3
• NSAIDs, including naproxen, may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure 3

Gastrointestinal Risks

• Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs 3
• A study found that misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding 4
• Proton pump inhibitors (PPIs) have been shown to be effective in preventing the development of gastric and duodenal ulcers in high-risk patients taking NSAIDs 5

Cardiovascular Risks

• Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether 3
• A study found that adding misoprostol to standard intravenous proton pump inhibitor protocol did not improve the outcome of aspirin/NSAID-induced upper gastrointestinal bleeding 6

Prevention and Management

• Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs 3
• PPI therapy is also beneficial in healing NSAID-induced ulcers and preventing their recurrence in patients requiring ongoing NSAID therapy 5