Anilides. Analgesics and antipyretics
ATC code: N02BE01 (Paracetamol)
Brand names
Tylenol, Panadol, Ofirmev
The analgesic mechanism is not fully established. Proposed pathways include central COX-2 inhibition and, per current data, interaction with the endocannabinoid system via the active metabolite AM404. Unlike NSAIDs, it does not appreciably inhibit peripheral COX and has no anti-inflammatory effect. The antipyretic effect is mediated through the hypothalamic thermoregulatory center.
First line
Paracetamol is first-line for symptomatic fever reduction in adults and children. Pediatric dose: 15 mg/kg every 4–6 hours, up to 60 mg/kg/day. Lowering fever does not speed recovery from infection and is only used when fever is poorly tolerated. In children with a history of febrile seizures, paracetamol does not prevent recurrences.
First line
In mild to moderate migraine attacks, paracetamol 1000 mg is an acceptable first-line option in patients who cannot tolerate NSAIDs or triptans. Efficacy in severe attacks is lower than triptans and NSAIDs. Taking it early in the attack (within 30 minutes of pain onset) improves efficacy.
First line
Mild to moderate pain is a core indication. Adults: 500–1000 mg every 4–6 hours, up to 4 g/day in healthy adults, up to 3 g/day in the elderly, chronic alcohol users, or malnourished patients. Paracetamol is less effective than NSAIDs for inflammatory pain (osteoarthritis, dysmenorrhea) but is preferred in patients with NSAID contraindications: peptic ulcer, anticoagulants, renal failure, heart failure, aspirin-exacerbated respiratory disease.
Second line
In current OA 2022 and 2019 recommendations, paracetamol has moved to a second-line position in osteoarthritis in favor of topical NSAIDs and short-course systemic NSAIDs. It is recommended as an alternative in patients with NSAID contraindications. Long-term paracetamol for osteoarthritis has not shown substantial benefit over placebo in recent systematic reviews.
2 pairs found. Sorted from critical to minor.
Mechanism
Paracetamol above 2 g/day for more than 7 days raises INR by 1–3 units. The mechanism is not fully understood – the NAPQI metabolite probably inhibits vitamin K-dependent γ-carboxylation. A single 0.5–1 g dose is clinically insignificant. Occasional use up to 2 g/day for less than 7 days is safe.
Management
In warfarin-treated patients, paracetamol remains the preferred analgesic over NSAIDs. For courses longer than 7 days or doses above 2 g/day, check INR at 7 days. After the course ends, recheck INR in 7–10 days.
Sources
Mechanism
No direct pharmacokinetic interaction. Concurrent use at standard doses is safe.
Management
No dose adjustment is required.
Sources
Boxed warning
Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.
Paracetamol is first-line for pain and fever in any trimester (historically FDA category B; the FDA pregnancy categories were retired in 2015). Earlier observational studies linked long-term third-trimester use to ADHD and autism, but the largest study to date — a Swedish sibling-controlled cohort (Ahlqvist VH et al. JAMA. 2024;331(14):1205–1214, n = 2.48 million children) — found no association after controlling for familial factors. Current view: standard doses for indicated use remain a safe option; unnecessary long-term high-dose use is still avoided.
Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.
paracetamol is evaluated for the following indications with varying evidence strength: Fever (evidence tier A), Migraine (evidence tier A), Mild to moderate pain in adults (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of paracetamol (≥ 1 in 100): At recommended doses, adverse effects are rare and minimal. See the Safety section for uncommon and serious reactions.
FDA category B. Paracetamol is first-line for pain and fever in any trimester (historically FDA category B; the FDA pregnancy categories were retired in 2015). Earlier observational studies linked long-term third-trimester use to ADHD and autism, but the largest study to date — a Swedish sibling-controlled cohort (Ahlqvist VH et al. JAMA. 2024;331(14):1205–1214, n = 2.48 million children) — found no association after controlling for familial factors. Current view: standard doses for indicated use remain a safe option; unnecessary long-term high-dose use is still avoided.
Compatible with breastfeeding. Minimal concentrations in milk; one of the preferred analgesics in lactation.
paracetamol is contraindicated in: Severe hepatic impairment; Acute hepatitis; Hypersensitivity. Full list in the Safety section.
Hepatotoxicity in overdose. Daily doses above 4 g in adults (above 3 g in at-risk patients) can cause severe acute liver injury up to hepatic failure. The antidote is N-acetylcysteine.
paracetamol is a leading cause of acute liver failure worldwide. Safety critically depends on adhering to the maximum daily dose.
paracetamol lacks anti-inflammatory activity. Inflammatory conditions are best treated with NSAIDs when not contraindicated.
in children the dose is strictly 15 mg/kg per dose no more often than every 4–6 hours and no more than 4–5 times daily. Overdose in children is hepatotoxic.