Paracetamol (Acetaminophen) — Medication Guide, Uses & Safety — Uses, Dosage & Side Effects | MyMedicPlus

Paracetamol (known as acetaminophen in the United States and Canada — brand names Tylenol, Panadol, Calpol, Paramol) is one of the most widely used over-the-counter medications in the world, available without prescription in virtually every country. It belongs to the analgesic (pain-relieving) and antipyretic (fever-reducing) drug class. Paracetamol is the recommended first-line analgesic for mild-to-moderate pain in adults and children, and is the preferred OTC pain reliever and antipyretic during pregnancy. It is included on the WHO Model List of Essential Medicines and is one of the most prescribed and self-administered medicines globally. It is available in numerous formulations: standard tablets (500 mg), caplets, dispersible tablets, oral liquid suspension (for infants and children — 120 mg/5 mL, 250 mg/5 mL), effervescent tablets, suppositories (for children who cannot take oral medicine), and intravenous injection (1 g/100 mL for hospital use). Paracetamol is also a component of many combination medicines for cold, flu, sinus congestion, menstrual pain, and migraine — making it essential that patients read labels carefully to avoid accidental double dosing from multiple paracetamol-containing products taken simultaneously. When used at recommended doses in people without pre-existing liver disease or excessive alcohol use, paracetamol is extremely safe. Its primary risk is hepatotoxicity (liver damage) from overdose — making dose awareness critical.

Paracetamol is used for a wide range of on-label pain and fever conditions across all age groups from 2 months of age. It relieves mild-to-moderate pain including: headache and tension headache, dental pain and toothache, muscle aches and myalgia, back pain (low back pain — it is NICE-recommended first-line OTC analgesia, though evidence for benefit over placebo in non-specific back pain is modest), neck and shoulder pain, minor arthritic pain and joint discomfort, sore throat, earache, cold and flu symptoms, post-vaccination pain and fever, and menstrual pain (dysmenorrhea — though NSAIDs are more effective for menstrual cramps). It is the recommended OTC analgesic and antipyretic in all trimesters of pregnancy. It effectively lowers elevated body temperature (fever) caused by infections, inflammatory conditions, or post-vaccination immune responses. In hospital settings, IV paracetamol is used as an important component of multimodal post-operative analgesia, reducing opioid requirements by approximately 20–30%. For mild-to-moderate osteoarthritis, paracetamol is recommended as first-line analgesic, particularly when NSAIDs are contraindicated. It is commonly recommended or prescribed by general practitioners, pediatricians, dentists, pharmacists, obstetricians, and surgeons.

The precise mechanism of paracetamol's analgesic and antipyretic action is more complex than previously understood and involves multiple pathways. Primarily, paracetamol inhibits the synthesis of prostaglandins in the central nervous system — specifically in the brain and spinal cord — by blocking COX-1 and COX-2 cyclooxygenase enzymes in a centrally preferential manner. This reduces prostaglandin E2 (PGE2) levels in the hypothalamus, which normally act to elevate the body's temperature set point during infection or inflammation — reducing it restores the thermostat toward normal temperature, promoting heat dissipation through sweating and peripheral vasodilation. For analgesia, reduced central prostaglandin synthesis lowers the pain sensitivity (hyperalgesia) set by inflammatory mediators at spinal cord synapses. Unlike NSAIDs, paracetamol has very minimal inhibitory effect on peripheral COX enzymes — which is why it does not produce significant anti-inflammatory effects in tissues (making it less effective for inflammatory arthritis than NSAIDs) and why it spares the protective gastric prostaglandins — making it gentler on the stomach. Additional proposed analgesic mechanisms include: indirect activation of cannabinoid CB1 receptors via the endocannabinoid system (through its metabolite AM404); modulation of descending serotonergic pain-inhibitory pathways in the brainstem; and inhibition of a third COX isoform variant (COX-3) in the CNS. These complementary mechanisms explain its analgesic efficacy despite minimal peripheral COX inhibition.

Typical adult dose: 500–1000 mg every 4–6 hours as needed, with a maximum dose of 4000 mg (4 g) per 24-hour period. Doses should not be given more frequently than every 4 hours. For adults with liver disease, cirrhosis, chronic heavy alcohol use, low body weight (under 50 kg), malnutrition, or those who are fasting, the maximum daily dose should be reduced to 2000 mg (2 g) per 24 hours. Children's doses are strictly weight-based — approximately 15 mg/kg every 4–6 hours, up to a maximum of 4 doses in 24 hours; always use the correct paediatric formulation and the calibrated measuring syringe provided. Babies from 2 months: 60 mg single dose. Children aged 2–11 years: doses range from 120 mg to 500 mg per dose depending on weight. Teenagers (12–17 years): 480–1000 mg per dose. Available as standard and effervescent tablets, dispersible sachets, oral liquid for children, suppositories, and IV infusion. IV paracetamol in hospital: 1000 mg (or 15 mg/kg in children) infused over 15 minutes every 4–6 hours as needed (max 4 g/day adults, 60 mg/kg/day in children). Never exceed the stated maximum daily dose under any circumstances.

Paracetamol is exceptionally well tolerated at recommended doses in healthy individuals — it produces very few side effects compared to most other analgesics. Unlike NSAIDs, it does not irritate the stomach lining, does not impair kidney function at therapeutic doses, does not increase bleeding time, does not raise blood pressure, and is not associated with cardiovascular risk. It is safe in pregnancy at all trimesters, safe in the elderly, safe in those with chronic kidney disease, and safe in patients with peptic ulcer disease — making it the analgesic of choice for patients who cannot tolerate NSAIDs. The most serious and critical adverse effect is hepatotoxicity (liver damage) — which is dose-dependent. Paracetamol overdose (acute ingestion of more than 7.5–10 g in a healthy adult, or less in vulnerable groups) causes the toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI) to accumulate in the liver when its normal detoxification pathway (conjugation with glutathione) is overwhelmed — leading to hepatocyte necrosis, which can progress to acute liver failure and death if not treated promptly with N-acetylcysteine. Chronic use with regular heavy alcohol consumption also depletes glutathione stores, increasing hepatotoxicity risk at lower doses. Early symptoms of paracetamol overdose (nausea, malaise) may appear minimal in the first 12–24 hours, with severe liver failure developing 24–72 hours later — early treatment before symptom onset is critical. Rare: severe hypersensitivity reactions (anaphylaxis, fixed drug eruption, Stevens-Johnson syndrome — extremely uncommon). Blood disorders (thrombocytopenia, neutropenia) have been reported rarely.

The single most important safety warning for paracetamol is to never exceed 4 g (4000 mg) in any 24-hour period in healthy adults, and 2 g per day in high-risk groups (liver disease, chronic heavy alcohol use, low body weight, malnutrition, fasting). Accidental paracetamol overdose is one of the leading causes of acute liver failure in the UK and USA — it often occurs because patients do not realize that many combination products they take simultaneously (Lemsip, DayNurse, NightNurse, co-codamol, Tylenol PM, Nyquil) already contain full doses of paracetamol. Always read the ingredient label of every medicine you take and check whether it contains paracetamol before adding standard paracetamol tablets. If you think you or someone else may have taken too much paracetamol — even if they feel completely well — seek emergency medical attention immediately. Do not wait for symptoms to develop. The antidote (N-acetylcysteine) is most effective when given early, within 8–10 hours of ingestion. Drug interactions: paracetamol at regular therapeutic doses (1 g 3–4 times daily) modestly increases warfarin anticoagulant effect (raises INR by approximately 0.3–0.5) — more frequent INR monitoring is recommended for anticoagulated patients using regular paracetamol. Rifampicin and alcohol induce liver enzymes that increase NAPQI production from paracetamol — lowering the overdose threshold. Cholestyramine reduces paracetamol absorption when taken simultaneously — take at least 1 hour apart. Paracetamol is safe in patients with G6PD deficiency (unlike some NSAIDs). It is safe in aspirin-sensitive asthma (unlike NSAIDs). For patients with chronic liver disease or cirrhosis: use the lowest effective dose with the longest possible dosing interval, under medical supervision.