paracetamol

Last edited 11/2023 and last reviewed 11/2023

Paracetamol is one of the most popular over-the-counter analgesic preparations, used regularly by millions of people throughout the world. It is also an ingredient of other brand name analgesic preparations, for example calpol, anadin extra and lemsip.

• has a unique clinical pharmacological profile that includes potent analgesic and antipyretic effects and no or little anti-inflammatory activity as well as minor gastrointestinal, renal, and vascular side effects (1)
  
  
• typical licensed indications for paracetamol in adults include treatment of most painful and febrile conditions, including headache, neuralgia, sore throat, and rheumatic pain (2)
  
  
• acetaminophen (paracetamol; N-acetyl-p-aminophenol) is the active metabolite of phenacetin
  • unlike phenacetin, paracetamol is not carcinogenic (1)
    
    
• oral paracetamol has excellent bioavailability with peak plasma concentrations occurring within 30-60 min after ingestion
  • plasma t1/2 is about 120 min
    
    
• binds to plasma proteins less than NSAIDs and diffuses throughout most body fluids.

Potential risk factors for hepatotoxicity with paracetamol include (2):

• dry body weight under 50 kg
• use of paracetamol in older or frail patients
• cachexia
• renal insufficiency
• chronic malnutrition
• chronic dehydration
• decompensated liver disease
• chronic alcohol consumption or regular consumption of alcohol in excess of recommended amounts
• long term treatment with liver enzyme inducing drugs, such as
  • carbamazepine, phenytoin, primidone, rifampicin, phenobarbital, St John's Wort, or other drugs that induce liver enzymes

Reference:

• Freo U, Ruocco C, Valerio A, Scagnol I, Nisoli E. Paracetamol: A Review of Guideline Recommendations. J Clin Med. 2021 Jul 31;10(15):3420. doi: 10.3390/jcm10153420. PMID: 34362203; PMCID: PMC8347233.
• Caparrotta T M, Carduff E, Dear J W. Paracetamol use in adults BMJ 2023; 383 :e070753 doi:10.1136/bmj-2022-070753