paracetamol
Non-opioid analgesic; antipyretic· Brands: Panadol, Calpol, Tylenol, ParalenIVPOPR
Mechanism of action
Paracetamol has analgesic and antipyretic activity. Its precise mechanism is not fully understood, but it is thought to inhibit cyclooxygenase enzymes centrally, reducing prostaglandin synthesis in the hypothalamus and other CNS sites. It does not have significant peripheral anti-inflammatory action. It may also modulate endocannabinoid and TRPV1 signalling.
Pharmacokinetics
Well absorbed after oral administration, with peak plasma concentrations in 30-60 minutes. It is metabolised primarily in the liver by conjugation (glucuronidation and sulfation). A minor pathway via CYP2E1 produces the toxic metabolite NAPQI, which is normally inactivated by glutathione. The elimination half-life is about 2-3 hours. It is excreted as inactive conjugates in the urine.
Indications & dosing
Mild to moderate pain
Maximum 4 g/day; caution in hepatic impairment.
- adult · PO: 500–1000 mg every 4-6 hours · Maximum 4 g/day; caution in hepatic impairment.
Fever
Maximum 4 g/day; caution in hepatic impairment.
- adult · PO: 500–1000 mg every 4-6 hours · Maximum 4 g/day; caution in hepatic impairment.
Mild to moderate pain
Weight-based dosing; maximum 60 mg/kg/day (not exceeding 4 g/day).
- pediatric · PO: 10–15 mg/kg every 4-6 hours · Weight-based dosing; maximum 60 mg/kg/day (not exceeding 4 g/day).
Fever
Weight-based dosing; maximum 60 mg/kg/day (not exceeding 4 g/day).
- pediatric · PO: 10–15 mg/kg every 4-6 hours · Weight-based dosing; maximum 60 mg/kg/day (not exceeding 4 g/day).
Contraindications & precautions
- Hypersensitivity to paracetamol or any excipient · Screening should include previous anaphylactic reactions to paracetamol.
- Severe hepatic impairment or active liver disease · Risk of hepatotoxicity; avoid unless specialist advice.
- Chronic alcohol use/abuse · Increased risk of hepatic injury; reduce dose and monitor.
- Avoid concurrent use of other paracetamol-containing products to prevent accidental overdose.
- Use with caution in mild to moderate hepatic impairment or chronic alcohol use; consider dose reduction and monitor LFTs.
- Use with caution in severe renal impairment; consider dose interval adjustment.
- Advise patients on symptoms of liver injury and to seek urgent medical attention if overdose is suspected.
Adverse effects
- Nausea
- Rash
- Severe cutaneous reactions (SJS/TEN)serious
- Anaphylaxisserious
- Hepatotoxicity (overdose)serious
- Thrombocytopeniaserious
- Agranulocytosisserious
Interactions
- warfarinmoderateIf paracetamol is required, it is advisable to use the lowest effective dose for the shortest duration. Monitor the INR within 3 to 5 days after starting or stopping paracetamol, and regularly during concurrent use (e.g., every 1 to 2 weeks). Consider alternative analgesics if the INR rises significantly or if bleeding occurs. Ensure patient education about signs of bleeding.
Renal & hepatic adjustment
- eGFR 0–29: Reduce dose or extend dosing interval; maximum 3 g/day for adults or as per local protocol.
- Hepatic impairment (mild): Use with caution; consider lowest effective dose for shortest duration.
- Hepatic impairment (moderate): Reduce dose; consider maximum 2-3 g/day (as per local protocol) and monitor liver function.
- Hepatic impairment (severe): Avoid or use with extreme caution; consider alternative analgesia. (avoid)
Monitoring, pregnancy & toxicity
- Liver function tests · In long-term therapy or high doses.
- Paracetamol plasma concentration · In suspected overdose.
- Renal function · In severe renal impairment or prolonged therapy.
- Pregnancy: Paracetamol is the analgesic of choice in pregnancy; use the lowest effective dose for the shortest duration.
- Toxicity: Early features: nausea, vomiting, abdominal pain, sweating; often asymptomatic initially. · Monitor paracetamol concentrations and liver function; consider activated charcoal if within 1-2 hours of ingestion.
- Toxicity: Hepatotoxicity (48-96 hours): right upper quadrant pain, jaundice, elevated transaminases, coagulopathy, encephalopathy. · Administer N-acetylcysteine (IV) as antidote; monitor liver function and INR; consider transfer to specialist centre.
- Toxicity: Renal failure (less common): oliguria, elevated creatinine. · Supportive care; monitor renal function; seek specialist advice.
Antidotes & reversal
- Acetylcysteine (N-acetylcysteine) · Replenishes glutathione; most effective within 8-10 h of ingestion. Add activated charcoal if within 1-2 h.
Clinical notes
First-line for mild to moderate pain and fever. Safe at recommended doses but caution in chronic liver disease and in patients with hepatic impairment. Maximum daily dose is typically 4 g in adults (lower in some regions). Overdose causes hepatocellular necrosis; early antidote is N-acetylcysteine. Consider total dose from combination products.
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BNF; local formulary