Are there any untoward synergistic effects in taking a combination of acetaminophen plus ibuprofen?
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., 1,000 mg acetaminophen plus 400 mg ibuprofen [0] — 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.
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?
[0] Dosage based on studies showing that higher doses of ibuprofen were no better at pain relief than 1200 mg/day.
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Reference 1 refers to studies that trail various combinations of analgesics. Of note is the study concerning paracetamol (acetaminophen) and ibuprofen.
The study compared the adverse effects of 4 groups:
paracetamol
ibuprofen
paracetamol and ibuprofen, and;
placebo.
They found "adverse events (signi?cant difference)" consisted of:
Vomiting: 24%–32%
Drowsiness: 5%
Abdominal pain: 3%–10%
And stated that the "paracetamol group was drowsier than other groups."
Reference 1 states: "Combining [the two] analgesics may increase the incidence of adverse effects."
A similar clinical trial was described in Reference 2. The paper found that adverse events were "numerically higher in the groups receiving combination tablets."
From this it can concluded that the likelihood of experiencing adverse effects is increased by combination of the two analgesics.
I could not find anything solid in regards to your last question. The increased likelihood of experiencing adverse effects may be due to the two agent's similar mechanism of action. Reference 3 states: "Due to their mechanisms of action, using paracetamol and ibuprofen together theoretically increases the risk of renal and hepatic toxicity." It is possible that this extends to other adverse effects.
References
Combining Paracetamol (Acetaminophen) with Nonsteroidal Antiin?ammatory Drugs: A Qualitative Systematic Review of Analgesic Ef?cacy for Acute Postoperative Pain, www.endoexperience.com/documents/APAPOngetal.pdf Paracetamol, ibuprofen, or a combination of both drugs against knee pain: an excellent new randomised clinical trial answers old questions and suggests new therapeutic recommendations, ard.bmj.com/content/70/9/1521.full Evidence that alternate dosing of paracetamol and ibuprofen in children with fever may reduce temperature: other benefits uncertain www.bpac.org.nz/BPJ/2014/July/docs/BPJ62-news.pdf
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