What you need to know A 65 year old retired engineer has experienced a flare up in the pain he experiences with his osteoarthritic knee. While seeing his general practitioner (GP) about a skin lesion, he mentions the knee problem and asks if he should use paracetamol to manage the pain. The patient is overweight and physically inactive. Paracetamol (acetaminophen) is one of the most widely used over-the-counter drugs around the world for the treatment of pain.1 More than 100 different preparations, which contain paracetamol alone or in combination with other substances (eg, non-steroidal anti-inflammatory drugs or NSAIDs, caffeine, and tramadol) are available.2 Current understanding is that paracetamol acts by inhibiting the cyclooxygenase (COX) enzymes through metabolism of the peroxidase function of these isoenzymes. It is less certain if its action is mediated by inhibition of COX-1, COX-2, or COX-3 enzymes.234 Paracetamol is inexpensive in most countries and is generally considered safe. This contributes to its widespread use. Paracetamol is available in immediate release (short acting) and modified release (long acting) preparations. In December 2017, the European Medicines Agency recommended suspending the marketing of modified release paracetamol because of concerns about a rise in overdose events and ensuing complications,5 although the modified release preparations are still widely available in countries such as Australia, New Zealand, and the US. …