מתוך medicontext.co.il
WESTPORT, CT (Reuters Health) – Patients who take acetaminophen at dosages exceeding 2 grams per day are at nearly four times the risk of peptic ulcer compared with non-users, investigators report. The risk skyrockets when nonsteroidal anti-inflammatory drugs (NSAIDs) and high-dose acetaminophen are taken together.
Dr. Luis Alberto Garcםa Rodrםguez, of the Centro Espaסol de Investigaciףn Farmacoepidemiolףgica in Madrid, Spain, and Dr. Sonia Hernבndez-Dםaz, of Harvard School of Public Health in Boston, evaluated the association between acetaminophen and NSAIDs and upper GI complications. They also evaluated the effects of various gastroprotective agents.
The cases were 2105 patients, ages 40 to 79, diagnosed with peptic ulcer. The 11,500 control subjects were matched by age and gender. The researchers' findings appear in Epidemiology for September.
Use of acetaminophen at any dose was associated with a relative risk of 1.3. Adding NSAIDs to acetaminophen at less than 2 grams daily did not increase the 4.1-fold increased risk associated with NSAID use alone.
When the daily dosage was more than 2 grams, the relative risk increased to 3.6. However, when NSAIDs were combined with acetaminophen at 2 grams per day or more, the relative risk was 13.2.
Drs. Rodriguez and Hernandez-Diaz note that "acetaminophen is a weak nonselective inhibitor of both isoforms of cyclooxygenase." The exacerbated risk associated with high-dose acetaminophen and NSAIDs is likely due to augmentation of cyclooxygenase inhibition, the investigators suggest.
The researchers also report for the first time that the risks associated with the newer NSAIDs etodolac, meloxicam and nabumetone are comparable to those of "the average NSAID effect." Dosage was the most significant factor associated with risk due to NSAIDs, although longer plasma half-life or slow-release formulation also increased the risk.
"Apazone was the only NSAID that at the daily doses used (600 mg to 1200 mg) was associated with a relative risk of upper GI complications distinctively greater than the average NSAID relative risk," the two analysts report.
H2 receptor antagonists did not lower the risk of peptic ulcers. However, omeprazole, misoprostol, and nitrates decreased the risk among users of NSAIDs.
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