Does concomitant use of paracetamol potentiate the gastroduodenal mucosal injury associated with aspirin? A prospective, randomised, pilot study

Aliment Pharmacol Ther. 2012 Aug;36(4):391-7. doi: 10.1111/j.1365-2036.2012.05200.x. Epub 2012 Jun 29.


Background: Paracetamol is commonly prescribed for first-line symptomatic treatment in patients with osteoarthritis and aspirin is often co-administered for cardiovascular prophylaxis. It is not known if an interaction exists between aspirin and paracetamol in regards to gastroduodenal mucosal injury.

Aim: To investigate whether or not co-administered aspirin with paracetamol results in an increased rate of endoscopic gastroduodenal mucosal injury as compared to either agent alone.

Methods: In this prospective, double-blind, randomised, three-arm, placebo- and active-controlled, parallel-group pilot study healthy adult subjects (18-75 years old) with a normal baseline trans-nasal oesophagogastroduodenoscopy (TN-EGD), received oral paracetamol 4000 mg q.d.s. (n = 21), aspirin 325 mg q.d.s. (n = 19) or paracetamol 4000 mg q.d.s. and aspirin 325 mg q.d.s. (n = 20). Upper gastrointestinal mucosal injury was evaluated after 7 days of treatment with TN-EGD.

Results: The rate of gastric ulcers in subjects receiving paracetamol (0/21, 0%) alone or aspirin (3/19, 16%) or both (2/20, 10%) was not different. There were, however, significantly more subjects with one or more lesions (erosion or ulcer) per subject in the paracetamol and aspirin (16/20, 80%) treated subjects as compared to the aspirin (8/19, 42%, P < 0.001) or the paracetamol (3/21, 14%, P < 0.01) exposed subjects. The mean number of lesions per subject was also greater (7.9 vs. 0.7, P < 0.01) in those treated with aspirin and paracetamol compared to paracetamol alone.

Conclusions: Co-administration of paracetamol and aspirin was not associated with a significant difference in endoscopic ulcer rates compared to either drug alone. There was a strong signal for increased endoscopic erosions and ulcers in the combined group compared to either aspirin or paracetamol alone.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / adverse effects*
  • Adolescent
  • Adult
  • Aged
  • Analgesics, Non-Narcotic / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / adverse effects*
  • Double-Blind Method
  • Drug Combinations
  • Drug Interactions
  • Duodenal Ulcer / chemically induced*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Statistics as Topic
  • Stomach Ulcer / chemically induced*
  • Young Adult


  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Acetaminophen
  • Aspirin