Are there any untoward synergistic effects in taking a combination of acetaminophen plus ibuprofen?

Question

A number of years ago, it became popular to advocate a combination of acetaminophen and ibuprofen (or other non-steroidal anti-inflammatory medication) at the usual higher doses (e.g. 1,000mg acetaminophen plus 400mg ibuprofen*) because studies had shown increased efficacy over either medication alone in pain relief. In fact, I believe in Europe there are over-the-counter products that combine the two.My question: does the combination of the two medications taken together have increased risks above the combined risks of the individual medications? If so, is the mechanism of the untoward synergistic effect known?*

Answer 1

Administration of acetaminophen and ibuprofen (or an alternative NSAID) concurrently is safe at recommended daily doses. This is an example of multimodal analgesia, which is typically more effective than individual administration. The main reason that concurrent administration is safe is due to the fact that acetaminophen is mainly metabolized in the liver, while ibuprofen is predominately metabolized in the kidneys. Also, NSAIDs can cause or exacerbate gastric ulcers, gastritis and bleeding secondary to inhibiting the COX-1 enzyme and decreasing the production of gastric prostaglandins. Although concurrent use of acetaminophen and NSAIDs is safe and therapeutic, it is always best practice to take the minimum amount of medication, while achieving adequate pain relief, to reduce the risk of adverse affects.