Opioid Resource Center

Opioid Resource Center

November 07, 2017
3 min read

Combined acetaminophen, ibuprofen produces similar amount of pain relief as opioids in ED patients

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Andrew Chang
Andrew K. Chang

ED patients with acute extremity pain had neither clinically important nor statistically significant differences in pain reduction at 2 hours when receiving a single dose of ibuprofen and acetaminophen or several different combinations of opioids and acetaminophen, according to findings recently published in JAMA.

Study lead author Andrew K. Chang, MD, MS, of the department of emergency medicine at Albany Medicine College in New York, told Healio Family Medicine the idea for the study came while travelling overseas, where some countries have analgesics that combine ibuprofen and acetaminophen into one tablet.

“I was struck at what I thought was a simple yet obvious combination of two different over-the-counter analgesics and what that could mean in terms of nonopioid pain control,” he said. “In designing the study, we didn’t think Tylenol or Motrin alone was adequate to treat acute severe extremity pain, but we did think that perhaps the combination of the two were enough to provide pain relief on par with commonly used opioids.”

Chang also wrote that no other single study has compared the effects of the three most commonly used opioid analgesics in the ED. He and his colleagues randomized patients at two EDs in New York City to receive either 5 mg of hydrocodone and 300 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 30 mg of codeine and 300 mg of acetaminophen; or 400 mg of ibuprofen and 1000 mg of acetaminophen. Each cohort consisted of 104 participants. The mean age of the patients in the study was 37 years, 48% were women, and all had pain in either the arm or the leg.

The primary outcome was the between-group difference in decline in pain 2 hours after taking the analgesic. Pain intensity was assessed using an 11-point numerical rating scale that defined 0 as no pain and 10 as worst possible pain. The predefined minimum clinically important difference was 1.3 on this scale. The mean baseline pain score of all participants was 8.7.

Chang and colleagues analyzed the results from 411 patients and found that after 2 hours, the mean pain score decreased by 3.5 (95% CI, 2.9–4.2) in the hydrocodone and acetaminophen group; by 4.4 (95% CI, 3.7–5) in the oxycodone and acetaminophen group; by 3.9 (95% CI, 3.2–4.5) in the codeine and acetaminophen group; and by 4.3 (95% CI, 3.6–4.9) in the ibuprofen and acetaminophen group. There was no significant difference in pain reduction at 1 or 2 hours among the participants. “It is important to understand that this study was limited to patients seen and treated in an emergency department setting,” Chang said in an interview. “However, our findings imply that if patients receive adequate and comparable pain relief via a combination of non-opioids while in the ED, then patients could likely be treated with a similar non-opioid combination upon discharge as well.”


Chang acknowledged that findings from the acute setting may not translate into pain management in a primary care setting.

“We don’t know if the same pain relief would occur in a primary care setting. If primary care physicians chose to implement this into their practice then one caveat is that, at the dosages used in the study, a patient could only receive this combination of nonopioids up to three times a day since the maximum recommended daily dose of acetaminophen was recently changed to 3000 mg.”

In a related editorial, Demetrios N. Kyriacou, MD, PhD, department of emergency medicine at Northwestern University Feinberg School of Medicine, Chicago, also identified the difference in settings as an “important” limitation to Chang and colleagues’ findings.

“The effect of the ibuprofen and acetaminophen combination was assessed only in the ED. Typically, treatment regimens that provide adequate pain reduction in the ED setting are used for pain management at home. However, the study did not address whether the combination of ibuprofen and acetaminophen would provide similar pain reduction after the initial clinical assessment and treatment of acute pain in the ED setting,” he wrote. “In addition, a blanket approach restricting opioid medications may adversely affect certain patients who achieve better pain reduction from opioid vs. nonopioid medications.”

Still, Chang and colleagues’ findings provided “important evidence” about a potential strategy to address the opioid addiction crisis, and further studies are needed to assess the effectiveness of combining acetaminophen and ibuprofen in other clinical settings, Kyriacou concluded. – by Janel Miller

Disclosures: The authors report no relevant financial disclosures.