Recently, I heard on this health-related radio programme that it was better to take a half dose of paracetamol and a half dose of ibuprofen together, rather than the full dose of either one, for acute pain. Could anyone explain the reasons for this ? Could it be something along the lines of there being diminishing returns to higher doses, so you get more bang for the buck, as it were, for the first half of a dose than the second, but due to possible toxicity or drug interactions, two full doses are not recommended ?

In the same radio programme it was stated that caffeine also helps. Can anyone explain that ?

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    $\begingroup$ Welcome to Biology.SE! As stated in the FAQ, we cannot furnish medical advice on this site. I think this question is borderline on-topic for this site--as long as answers to this question focus on the biological reasons as to why some treatments may or may not be better than others, it should be fine, but if the discussion in any way deviates to discussing the clinical benefits of one treatment vs another, we will have to shut it down. $\endgroup$ – Daniel Standage May 30 '12 at 21:59
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    $\begingroup$ By "better" I take it you mean a more effective analgesic rather than better in terms of potential toxic effects, speed of onset/offset etc? $\endgroup$ – Rory M May 30 '12 at 22:12
  • $\begingroup$ Hello and thanks for the welcome. I am not asking for medical advice - sorry if that was the impression I gave. I am curious from a scientific perspective. I am interested from both the efficacy and toxicity point of view. $\endgroup$ – Joe King May 30 '12 at 22:25
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    $\begingroup$ It would help your point to remove the personal anectdote $\endgroup$ – David LeBauer Jun 1 '12 at 0:01
  • $\begingroup$ a start for someone researching the answer: en.wikipedia.org/wiki/Analgesic#Combinations $\endgroup$ – Michael Kuhn Jun 1 '12 at 12:14

There are many different reasons for an acute pain and inflammation (both directly via pain receptors, and indirectly via swelling etc.) plays not the least role in this phenomenon. Therefore the combination of a classic analgesic without anti-inflammatory activity (as paracetamol) with a strong anti-inflammatory agent (as ibuprofen) is a reasonable one and potentially alleviates the pain manifestations in more cases than a single administration of every agent.

You are right with you suggestion that the doubled dose could be dangerous: even though the complications of Paracetamol administrations are not often, they are very dramatic (acute liver failure) with rather pessimistic prognosis. This is why one generally tries to half the doses if combined with other similar-acting agents (historically paracetamol was for the long time a member of the non-steroid anti-inflammatory agents).

Caffeine is generally believed to be a pain reliever, especially as concerns the pains with migraine background (source). One review, however, points out that there are still not enough data to support this belief (source).


Whilst Alexander Galkin gives some great information, I think there's a fundamental reason why that particular pain relief strategy is best, and it hasn't been mentioned yet.

The reason is simply that when you take Ibuprofen or Paracetamol (a full dose) you can only take it once every 4 hours. However, the pain relief doesn't last for 4 hours, so if you take either or both together every four hours you will experience pain after the medication wears off and before you are allowed your next dose.

So instead you can follow either of two strategies:

  1. Take a full dose of Paracetamol at 0 hours, 4 hours, 8 hours, as well as taking a full dose of Ibuprofen at 2 hours, 6 hours, 10 hours. This will give you less time when no pain medication is in effect. But if your pain is inflammation related you might want to keep the anti-inflammatory effects of Ibuprofen topped up, so you can...
  2. Take a half dose of Paracetamol + a half dose of Ibruprofen every 2hours. This gives you a mix of pure pain relief and anti-inflammation and ensures minimum time when each medication has no effect.

I don't think human biology has to come into it (apart from the fact that you can take the two substances together with no ill effects), it's just a good pain-avoidance strategy.

  • $\begingroup$ Can you provide evidence that taking a full dose of paracetamol every 4 hours equals taking half dose every 2 hours? And that the pharmacokinetics of paracetamol are not influenced by ibuprofen? $\endgroup$ – nico Nov 14 '12 at 16:36

The only reason why caffeine helps with migraine pain is because the pain is caused by expanded blood vessels and caffeine's effect is to narrow the blood vessels. But how it helps with other types of pain I really can't imagine.

And it depends what you state as "full dose". The dose that can harm your liver for adults is 4g per day, so if you have Paracetamol 500mg you would have to take 8 pills to reach it. Would you possibly do it? If seeing pain doesn't go away after first pill .. ok, second one?

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    $\begingroup$ You should consider referencing your answers with appropriate sources where facts are not commonly accepted as fact. $\endgroup$ – Rory M Nov 14 '12 at 16:28

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