Ibuprofen × Paracetamol

Ibuprofen inhibits cyclooxygenase in peripheral tissues, while paracetamol acts mainly centrally and has no appreciable effect on gastric mucosa or platelet aggregation. With different targets, the analgesia adds up: the Cochrane review of single doses in acute postoperative pain found greater relief from the combination than from either drug alone. Paracetamol is not an NSAID, so the ibuprofen label warning against combining several NSAIDs does not apply to it.

The combination adds no symptoms of its own. What shows up after several days belongs to each drug separately: epigastric discomfort, nausea or dark stools from ibuprofen, and liver injury if paracetamol exceeds the 4 g per 24 hours set by the label. That ceiling drops with low body weight, prolonged fasting, regular alcohol use or existing liver disease.

Adults can take them together, or alternate them every 3-4 hours when pain is severe. Daily doses are counted separately for each: paracetamol stays within 4 g per 24 hours, ibuprofen at the lowest effective dose for the shortest time. In children under five with fever, NICE states not to give both at once and to consider alternating only if distress returns before the next dose is due.