Acetaminophen: Guidelines and evidence

Acetaminophen (also known as APAP and in Europe and UK, paracetamol) is the most commonly used drug in the US.  It is contained in over 600 prescription and over-the-counter medications.  It is widely available in the US as the brand name Tylenol and is also provided in a wide variety of combination preparations to treat colds, flu, insomnia, fever, allergies and pain. The Tylenol brand itself is almost a $2 billion market worldwide.

Pain patients often present to integrative healthcare providers already using the drug, either by prescription or OTC. Being aware of the clinical benefits and risks of acetaminophen can help patients make informed clinical decisions. While generally considered to be safe, the toxicity of acetaminophen is well recognized. It is a leading cause of liver failure and liver transplants in the US. It causes 56,000 ER visits and 2600 hospitalizations every year.[i],[ii]  Toxicity can occur both from an acute overdose as well as prolonged chronic use.

Acetaminophen is particularly dangerous because the highest recommended therapeutic dose of 3000 mg is close to the lethal dose of 10,000 mg. Overdose is too easy.

Acetaminophen is often cited in clinical practice guidelines as a first-line pharmacotherapy for a number of pain conditions. Clinical practice guidelines for acute and chronic low back pain, osteoarthritis, hip, knee, and shoulder pain make this recommendation. However review of the clinical evidence from randomized controlled trials calls these recommendations into question.

  • Acute low back pain. A high quality RCT as reported in Lancet in 2014 found no difference in recovery time from acute LBP with acetaminophen and placebo.
  • Chronic low back pain. A 2015 systematic review and meta-analysis found high quality evidence that showed no difference in pain intensity, functional capacity and quality of life between acetaminophen and placebo.[iii]
    • This same review also looked at osteoarthritis in the knee and hip. While drug therapy produced improvement in pain, the reduction was small (3-4 point on a 100-point pain scale) and was of questionable clinical significance.
  • Shoulder pain. A 2010 systematic review of the effects of various drug treatment of shoulder pain found insufficient evidence to support or refute the benefit of paracetamol for shoulder pain.[iv]

So the next time a patient reports that they are “only taking Tylenol,” having an evidence based discussion about their healthcare choices is appropriate.


[i] Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2018 Feb 23;2:CD003328.

[ii] Ye H, Nelson LJ, Gómez Del Moral M, Martínez-Naves E, Cubero FJ. Dissecting the molecular pathophysiology of drug-induced liver injury. World J. Gastroenterol. 2018 Apr 07;24(13):1373-1385

[iii] Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225. Published 2015 Mar 31. doi:10.1136/bmj.h1225

[iv] Murphy RJ, Carr AJ. Shoulder pain. BMJ Clin Evid. 2010;2010:1107. Published 2010 Jul 22.