Is diarrhea a side effect of aspirin (acetylsalicylic acid)?

Diarrhea as a Side Effect of Aspirin

Yes, diarrhea is a recognized side effect of aspirin, particularly noted with ticlopidine (which has a similar mechanism of action), where diarrhea occurs in approximately 12% of patients. 1

Gastrointestinal Side Effects of Aspirin

Aspirin can cause several gastrointestinal side effects, including:

• Common non-serious effects:

  • Abdominal pain
  • Dyspepsia (indigestion)
  • Nausea and vomiting
  • Diarrhea 1, 2

• Serious effects:

  • Gastrointestinal bleeding (most common serious adverse event)
  • Gastric ulceration
  • Perforation 1

Mechanism of Aspirin-Induced Diarrhea

Aspirin causes gastrointestinal side effects through two primary mechanisms:

1. Direct topical irritation of the gastrointestinal mucosa
2. Systemic inhibition of cyclooxygenase (COX) enzymes, which:
   • Reduces protective prostaglandin synthesis
   • Impairs the gastrointestinal mucosal barrier
   • Increases intestinal permeability 3, 4

These mechanisms can lead to increased intestinal permeability and irritation throughout the GI tract, potentially resulting in diarrhea.

Risk Factors for Aspirin-Induced Gastrointestinal Side Effects

The risk of experiencing diarrhea and other GI side effects from aspirin is increased by:

• Dose-dependent relationship - higher doses increase risk 1
• Advanced age - risk increases with each year of age (adjusted incidence rate ratio of 1.05) 1, 5
• Concurrent use of other medications:
  • NSAIDs (approximately quadruples the risk)
  • Anticoagulants
  • Selective serotonin reuptake inhibitors 1, 5
• History of gastrointestinal ulcers 1
• Female sex - women experience more GI adverse events than men (15.5% vs 12.8%) 2

Comparative Risk of Diarrhea

In comparative studies:

• Aspirin (18.5%) causes significantly more GI adverse events, including diarrhea, than ibuprofen (11.5%)
• The difference between ibuprofen and paracetamol (13.1%) was not significant 2

Minimizing Risk of Diarrhea and Other GI Side Effects

To minimize the risk of aspirin-induced diarrhea:

• Use the lowest effective dose - The optimal dose for cardiovascular prevention is not definitively established, but approximately 75-100 mg/day appears as effective as higher doses with fewer GI side effects 1
• Consider co-administration of protective agents like proton pump inhibitors or H2 blockers for patients at high risk of GI complications 1
• Avoid enteric-coated or buffered preparations as they do not clearly reduce adverse gastrointestinal effects 1

Special Considerations

• Low-dose aspirin (75-100 mg/day) carries less risk of GI side effects than higher doses but can still cause significant adverse events 1
• Over-the-counter use of aspirin carries relatively little risk of serious GI toxicity for most persons without risk factors 6
• Patients with rheumatoid arthritis tend to have higher rates of GI side effects than those with osteoarthritis 6

In summary, while diarrhea is a recognized side effect of aspirin, the risk is dose-dependent and influenced by individual risk factors. Using the lowest effective dose and appropriate precautions can help minimize this adverse effect.