How safe is acetaminophen (paracetamol) or ibuprofen for pain relief?

From the Guidelines

Acetaminophen (paracetamol) and ibuprofen are generally safe for short-term pain relief when taken as directed, but it is crucial to consider the potential risks and take the lowest effective dose for the shortest duration needed to control symptoms. For most adults, acetaminophen is safe at recommended doses (no more than 4 g daily, typically 500-1,000 mg every 4-6 hours) and is gentler on the stomach than ibuprofen, as noted in the 2021 study 1. However, exceeding these limits can cause serious liver damage, especially when combined with alcohol. Ibuprofen (typically 200-400 mg every 4-6 hours, not exceeding 1,200 mg daily for over-the-counter use) effectively reduces both pain and inflammation but carries risks of stomach irritation, ulcers, and increased cardiovascular events with prolonged use.

Some key considerations for the use of these medications include:

• The risk of hepatotoxicity with acetaminophen, particularly at high doses or with concomitant alcohol use 1
• The risk of gastrointestinal, cardiovascular, or renal adverse effects with ibuprofen, especially in patients with pre-existing conditions such as chronic kidney disease (CKD) or cardiovascular disease (CVD) 1
• The importance of assessing renal function before initiating NSAIDs or COX-2 inhibitors and avoiding their use in patients with an estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 1
• The potential benefits of adding a proton pump inhibitor (PPI) or misoprostol in patients at risk for upper gastrointestinal (UGI) events who require treatment with NSAIDs or COX-2 inhibitors 1

It is also worth noting that the efficacy of paracetamol in certain conditions, such as hand osteoarthritis, is still uncertain and may be small, as discussed in the 2019 study 1. Additionally, the use of oral analgesics, particularly NSAIDs, should be considered for a limited duration for relief of symptoms, with attention to the risk-benefit ratio, especially in patients at high risk of adverse effects 1. Ultimately, the decision to use acetaminophen or ibuprofen for pain relief should be made on a case-by-case basis, taking into account the individual patient's medical history, current medications, and potential risks and benefits.

From the FDA Drug Label

Ibuprofen tablets have been shown to be comparable to aspirin in controlling pain and inflammation and to be associated with a statistically significant reduction in the milder gastrointestinal side effects [see ADVERSE REACTIONS] Although it is not definitely known whether ibuprofen tablets causes less peptic ulceration than aspirin, in one study involving 885 patients with rheumatoid arthritis treated for up to one year, there were no reports of gastric ulceration with ibuprofen tablets whereas frank ulceration was reported in 13 patients in the aspirin group (statistically significant p < 0. 001) Gastroscopic studies at varying doses show an increased tendency toward gastric irritation at higher doses. However, at comparable doses, gastric irritation is approximately half that seen with aspirin Studies using 51Cr-tagged red cells indicate that fecal blood loss associated with ibuprofen tablets in doses up to 2400 mg daily did not exceed the normal range, and was significantly less than that seen in aspirin-treated patients

The safety of ibuprofen for pain relief is supported by studies showing a reduction in gastrointestinal side effects compared to aspirin. However, the risk of gastric irritation and bleeding still exists, particularly at higher doses.

• Key points:
  • Ibuprofen is associated with a lower risk of gastrointestinal side effects compared to aspirin
  • The risk of gastric irritation and bleeding increases with higher doses
  • Fecal blood loss associated with ibuprofen is significantly less than that seen with aspirin
• Clinical decision: Ibuprofen can be considered a relatively safe option for pain relief, but patients should be carefully monitored for signs and symptoms of gastrointestinal ulceration and bleeding, especially when taking higher doses or concomitantly with other medications that may increase the risk of bleeding 2. There is no information about acetaminophen in the provided drug labels.

From the Research

Safety of Acetaminophen and Ibuprofen

• Acetaminophen is known to be generally safe, but rare cases of anaphylaxis have been reported 3.
• Ibuprofen is also considered safe, but it can produce an unpredictable, idiosyncratic, type B reaction that may pose a major concern in clinical practice 4.
• Both acetaminophen and ibuprofen have been shown to be effective for pain relief, with ibuprofen providing faster relief and superior overall efficacy compared to acetaminophen in some studies 5, 6.

Potential Risks and Side Effects

• Acetaminophen can cause anaphylaxis, even in the absence of allergic reactions in the first dosing 3.
• Ibuprofen can cause hypersensitivity syndrome, a systemic disease defined by the triad of fever, rash, and internal organ involvement 4.
• The use of over-the-counter medications containing acetaminophen, aspirin, or ibuprofen can pose clinical challenges, especially when combined with prescription medications 7.

Comparison of Acetaminophen and Ibuprofen

• Ibuprofen has been shown to provide faster relief and superior overall efficacy compared to acetaminophen in some studies 5, 6.
• Acetaminophen is generally considered safer than ibuprofen, but both medications can cause side effects and interact with other medications 7, 3, 4.
• The choice between acetaminophen and ibuprofen depends on individual patient needs and medical history, and should be made under the guidance of a healthcare professional 7, 6.