Acetaminophen is a synthetic non-opioid analgesic and antipyretic.

 It acts mainly in the CNS, where it has several effects. It is a weak inhibitor of cyclo-oxygenase (COX)-2, an effect that lasts a short time (≤2 h) after a dose, but can also be anti-inflammatory through inhibition of peroxidase regeneration. The latter action, which prevents the oxidation of inactive COX to active COX, can be significant when peroxidase levels are low, e.g., in intact cells in the CNS, but not when peroxidase levels are much higher, e.g., with tissue damage and/or inflammation in the periphery.

It is possible that the analgesic effect of acetaminophen is dependent on synergy between some or all these mechanisms. Evidence of synergy between acetaminophen and NSAIDs suggests differing analgesic mechanisms.

Acetaminophen is widely used for acute musculoskeletal pains and acute headache. When used in combination with an opioid to treat postoperative pain, IV acetaminophen has an “opioid-sparing” effect and improves overall analgesia. Postoperative nausea and vomiting also is reduced, but only when the acetaminophen is administered before, during or immediately after surgery. The improvement correlated with the degree of pain relief (but not opioid use), suggesting a possible indirect or direct anti-emetic effect of acetaminophen.

Evidence of the efficacy of acetaminophen in combination with an opioid in the treatment of cancer pain is mixed. However, the RCTs that suggested no benefit were underpowered, and another RCT showed a small but clinically important additive effect in about one-third of patients despite the fact that half were already taking an NSAID or a corticosteroid.

Best Regards
Rebecca Pearson
Editorial Manager

Given that an acetaminophen regimen of 650 mg–1 g q.i.d. may pose a considerable pill burden to some patients with cancer.