What are the risks of taking other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) with naproxen?

Risks of Taking Multiple NSAIDs with Naproxen

Taking other NSAIDs concurrently with naproxen significantly increases the risk of serious adverse effects including gastrointestinal bleeding, acute renal failure, and hepatic injury, and should be avoided. 1

Increased Risks with Multiple NSAIDs

Gastrointestinal Complications

• Combining NSAIDs dramatically increases the risk of GI complications:
  • Using a single NSAID increases GI bleeding risk 7.3-fold
  • Using two or more NSAIDs increases this risk to 10.7-fold 1
  • NSAIDs cause serious GI events through blocking gastroprotective prostaglandin synthesis 2
  • Upper GI complications can include ulceration, bleeding, and perforation, which can be fatal 3

Renal Effects

• Multiple NSAID use significantly increases risk of acute renal failure:
  • Single NSAID use increases risk 3.2-fold
  • Two or more NSAIDs increases risk 4.8-fold 1
  • Long-term NSAID administration can result in renal papillary necrosis and other kidney injury 3
  • NSAIDs should be avoided in patients with pre-existing renal disease 2

Hepatic Effects

• Concurrent use of multiple NSAIDs increases hepatic injury risk:
  • Single NSAID use increases risk 1.2-fold
  • Two or more NSAIDs increases risk 2.2-fold 1
  • While hepatic damage from NSAIDs is rare, patients should be monitored for signs of liver toxicity 2

Cardiovascular Risks

• All NSAIDs, including naproxen, carry cardiovascular risks:
  • Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke 3
  • Potential for new hypertension or worsening of pre-existing hypertension 3
  • Fluid retention and edema 3
  • Combined NSAIDs may amplify these cardiovascular risks

High-Risk Populations

The following groups are at particularly high risk when taking multiple NSAIDs:

• Elderly patients (≥75 years) 4
• Patients with history of peptic ulcer disease or GI bleeding (2.5-4 times increased risk) 2
• Patients taking anticoagulants (3-fold increase in GI bleeding) 2
• Patients taking corticosteroids (2-fold increase in GI events) 2
• Patients taking low-dose aspirin concurrently 2
• Patients with cardiovascular disease or risk factors 3
• Patients with renal insufficiency 3

Pharmacological Basis for Avoiding Multiple NSAIDs

There is no pharmacological justification for using multiple systemic NSAIDs simultaneously 1. All NSAIDs work through the same mechanism - inhibition of cyclooxygenase enzymes - so combining them:

1. Does not provide additional therapeutic benefit
2. Significantly increases toxicity risks
3. May lead to overdose of the active ingredients

Recommendations for Patients Taking Naproxen

1. Never combine naproxen with other prescription or over-the-counter NSAIDs including:

   • Ibuprofen (Advil, Motrin)
   • Diclofenac
   • Celecoxib (Celebrex)
   • Aspirin (in anti-inflammatory doses)
   • Any other NSAID

2. Check medication labels carefully for active ingredients, as many over-the-counter pain and cold medications contain NSAIDs 5

3. If additional pain relief is needed, consider:

   • Acetaminophen/paracetamol (works through a different mechanism) 4
   • Consult with healthcare provider for alternative pain management options

4. For patients at high risk of GI complications who must take naproxen:

   • Consider gastroprotective agents such as proton pump inhibitors 2
   • Use the lowest effective dose for the shortest duration 3
   • Monitor for signs of GI bleeding (black stools, abdominal pain) 3

5. Monitor for warning signs of adverse effects:

   • GI symptoms: epigastric pain, dyspepsia, melena, hematemesis
   • Cardiovascular: chest pain, shortness of breath, weakness
   • Renal: decreased urination, fluid retention, edema
   • Hepatic: nausea, fatigue, jaundice, right upper quadrant pain 3

Remember that the simultaneous use of multiple NSAIDs has no therapeutic advantage but significantly increases the risk of serious adverse effects. This practice represents a serious public health concern, especially with increasing availability of over-the-counter NSAIDs 1.