Do Not Take Sulindac and Naproxen Together
Taking sulindac and naproxen together is not safe and should be avoided. Both are nonselective NSAIDs that work through the same mechanism, and combining them significantly increases your risk of serious gastrointestinal bleeding, kidney damage, and cardiovascular complications without providing additional therapeutic benefit 1.
Why This Combination Is Dangerous
Multiplied GI Bleeding Risk
- The risk of GI bleeding increases 3-6 times when combining NSAIDs 1
- Both drugs inhibit the same protective prostaglandins in your stomach lining
- The one-year risk of serious GI bleeding ranges from 1 in 2,100 in younger adults to 1 in 110 in adults over 75 1
- Adding a second NSAID compounds this risk without improving pain control
Compounded Kidney Toxicity
- Both sulindac and naproxen can cause acute renal failure, especially in patients with:
- Pre-existing kidney disease
- Heart failure
- Cirrhosis
- Concurrent use of ACE inhibitors or diuretics 1
- Sulindac is specifically noted as having higher potential for hepatic and renal complications 1
Cardiovascular Risks
- All NSAIDs increase blood pressure by an average of 5 mm Hg 1
- They worsen heart failure and increase risk of myocardial infarction
- Doubling NSAID exposure doubles these cardiovascular risks
What the Evidence Shows
The FDA drug labels explicitly state that naproxen-containing products should not be used concomitantly with other NSAIDs due to increased gastrointestinal toxicity with little to no increase in efficacy 2. The guideline literature consistently warns against combining NSAIDs 1.
Research comparing sulindac and naproxen shows they have equivalent efficacy when used individually 3, meaning there is no therapeutic advantage to combining them—only added risk.
What You Should Do Instead
Choose one NSAID only:
- If you need NSAID therapy, select either sulindac OR naproxen, not both
- Naproxen may be preferred as it has FDA approval for acute gout and appears to have less hepatotoxicity than sulindac 4
- Use the lowest effective dose for the shortest duration
If one NSAID isn't providing adequate pain relief:
- Add acetaminophen (up to 4g daily) instead of a second NSAID—this provides additive pain relief through a different mechanism 5, 6
- Consider adding a proton pump inhibitor (PPI) for GI protection if you have risk factors 1
- Discuss alternative pain management strategies with your physician
Critical Risk Factors
You are at especially high risk if you:
- Are over 65 years old
- Have a history of peptic ulcers or GI bleeding
- Take anticoagulants (warfarin, etc.)
- Take corticosteroids
- Have kidney disease, heart failure, or liver disease
- Take ACE inhibitors or diuretics 1
Common pitfall: Patients sometimes don't realize they're taking two NSAIDs because one is prescribed and one is over-the-counter (like ibuprofen or naproxen sodium/Aleve). Always check all your medications, including OTC products.