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? Dosage based on studies showing that higher doses of ibuprofen were no better at pain relief than 1200 mg/day.

Answer 1

What is usually recommended here in the US in terms of "round the clock" pain relief is an alternating schedule ie: take 400mg ibuprofen and then a couple hours later, take the 1000mg of acetaminophen and follow the 6 hour schedule for both medications, at their separate times. So for example: 400mg ibuprofen at 8am, 1000mg acetaminophen at 11am. Next dose ibuprofen at 2pm. Next dose acetaminophen at 5pm.

6 hours is the recommended time between doses as acetaminophen has a max dose of 4g per day (for a healthy adult), and a 6 hour schedule gives you 4, 1000mg doses. Ibuprofen has a max dose of 3200 mg per day and the 6 hour schedule for a 400mg dose is under the max amount.

What this does is allow the acetaminophen to peak when the dose of the ibuprofen is fading, and vise versa. This prevents gaps in pain coverage as you don't have to wait for the next dose of the ibuprofen or acetaminophen to start working again after it has already started to leave your system because the other medication is at its peak time, and providing you pain relief.

As for combining the two medications, NSAIDs are processed by your kidneys and acetaminophen by your liver. It is not harmful as long as the person follows instructions as to taking the medications (ie absolutely no drinking as that can cause liver damage with acetaminophen). I would also recommend staying well hydrated in addition as that is beneficial all around but there are no additional risks as long as the medication is taken correctly. Doses of over 400mg of ibuprofen are not any more effective than 400mg. Lower doses are better as they put less strain on the kidneys and are preferable if the effectiveness is not markedly increased, which is the case with ibuprofen. Alternating up to 400mg ibuprofen with acetaminophen also gives you more consistent coverage.