What are the side effects of naproxen (nonsteroidal anti-inflammatory drug)?

From the Guidelines

Naproxen can cause significant gastrointestinal side effects, including stomach pain, heartburn, nausea, and indigestion, and more serious effects like ulcers and bleeding, especially with long-term use, and therefore, it is recommended to take the lowest effective dose for the shortest duration possible, and to consult a healthcare provider before taking naproxen, especially for those with a history of heart disease, high blood pressure, kidney problems, or GI issues 1.

Common Side Effects

• Gastrointestinal side effects, such as stomach pain, heartburn, nausea, and indigestion
• Headache, dizziness, drowsiness, and fluid retention that may cause swelling in the extremities
• Increased blood pressure and risk of heart attack and stroke, particularly with prolonged use or in people with existing cardiovascular disease
• Kidney problems, especially in older adults or those with kidney disease
• Allergic reactions, though rare, may occur and can include rash, itching, or more severe symptoms like difficulty breathing

Serious Side Effects

• Ulcers and bleeding in the gastrointestinal tract, especially with long-term use
• Increased risk of heart attack and stroke, particularly with prolonged use or in people with existing cardiovascular disease
• Kidney problems, especially in older adults or those with kidney disease

Recommendations

• Take naproxen with food to reduce stomach irritation
• Use the lowest effective dose for the shortest duration possible
• Consult a healthcare provider before taking naproxen, especially for those with a history of heart disease, high blood pressure, kidney problems, or GI issues
• Monitor for signs of gastrointestinal bleeding, such as black stools or vomiting blood, and seek medical attention immediately if they occur 1

Special Considerations

• Patients with a history of peptic ulcer disease or gastrointestinal bleeding should use naproxen with caution and under close medical supervision 1
• Patients taking anticoagulants, such as warfarin, should use naproxen with caution and under close medical supervision 1

From the FDA Drug Label

Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported Naproxen, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Naproxen, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death Naproxen, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death Anemia is sometimes seen in patients receiving NSAIDs, including naproxen. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients.

The side effects of naproxen include:

• Hepatic reactions: Notable elevations of ALT or AST, severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure 2
• CV side effects: Serious CV side effects, such as MI or stroke, which may result in hospitalization and even death 2
• GI side effects: GI discomfort, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death 2
• Skin side effects: Serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death 2
• Hematological effects: Anemia, inhibition of platelet aggregation, and prolongation of bleeding time 2

From the Research

Naproxen Side Effects

• The most common side effects of naproxen include gastrointestinal issues such as dyspepsia and gastric or gastroduodenal ulcers 3
• Naproxen can cause gastrointestinal toxicity, ranging from dyspepsia and peptic ulcer disease to more serious complications such as haemorrhage or perforation 4
• Long-term use of naproxen can lead to an increased risk of gastrointestinal adverse effects, including ulcers and bleeding 5

Gastroprotection with Proton Pump Inhibitors

• Proton pump inhibitors (PPIs) such as omeprazole can be used to prevent NSAID-induced gastrointestinal damage 6, 4
• PPIs have been shown to be effective in preventing the development of gastric and duodenal ulcers in high-risk patients taking NSAIDs 4
• However, recent evidence suggests that the GI risks associated with NSAIDs can be potentiated when they are combined with PPIs 5

Comparison with Other NSAIDs

• Naproxen has been compared with other NSAIDs such as ibuprofen, diclofenac, and ketoprofen, and has been shown to be equally effective in treating arthritic symptoms 3, 6, 7
• Naproxen has a relatively long plasma half-life, allowing for twice-daily or once-daily dosing 7