What is Paracetamol?
Paracetamol (acetaminophen, APAP) is one of the most widely used analgesic and antipyretic medications worldwide. Known as paracetamol in most of the world and acetaminophen in North America and Japan, it is available over the counter in numerous formulations including tablets, capsules, liquid suspensions, suppositories, and intravenous preparations.
Paracetamol works primarily through inhibition of cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. Unlike NSAIDs, it has minimal anti-inflammatory activity and does not significantly affect platelet function or the gastric mucosa, making it the preferred first-line analgesic for many patient populations.
Dosing Guidelines
| Patient | Single Dose | Max Single Dose | Max Daily Dose | Interval |
|---|---|---|---|---|
| Child (1 month – 12 years) | 15 mg/kg | 20 mg/kg (max 1 g) | 75 mg/kg (max 4 g) | Every 4–6 hours |
| Adult / Child ≥50 kg | 500–1000 mg | 1000 mg | 4000 mg (4 g) | Every 4–6 hours |
| Adult <50 kg | 15 mg/kg | 1000 mg | 75 mg/kg (max 4 g) | Every 4–6 hours |
| Hepatic impairment | 500 mg | 500 mg | 2000 mg (2 g) | Every 6 hours |
Maximum 4 doses in 24 hours. Minimum interval between doses is 4 hours. Do not exceed the daily maximum under any circumstances.
Dosing Formulas
For example, with 120 mg/5 mL syrup:
Dosing Diagram
Pediatric Dosing
Pediatric dosing of paracetamol should always be based on body weight, not age. Age-based dosing charts are approximations and may lead to under- or overdosing. Key principles for pediatric dosing:
- Standard dose: 15 mg/kg per dose is the recommended single dose for children
- Loading dose: Some protocols use an initial dose of 20 mg/kg (particularly rectally due to slower absorption), followed by 15 mg/kg for subsequent doses
- Neonates: Reduced dosing (10-15 mg/kg) with longer intervals (every 6-8 hours) due to immature hepatic metabolism
- Always use the measuring device provided with the specific product. Kitchen spoons are inaccurate and should never be used.
- Check all medications for paracetamol content. Many cold/flu preparations contain paracetamol, risking inadvertent overdose.
Safety and Hepatotoxicity
Paracetamol is safe at recommended doses but has a narrow therapeutic index. The primary toxicity is dose-dependent hepatotoxicity caused by the toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine).
At therapeutic doses, NAPQI is rapidly conjugated by glutathione. In overdose, glutathione stores are depleted and NAPQI accumulates, causing hepatocellular necrosis. Risk factors for hepatotoxicity include:
- Chronic alcohol use: Induces CYP2E1, increasing NAPQI production while depleting glutathione
- Fasting/malnutrition: Reduced glutathione stores
- Liver disease: Reduced metabolic capacity; maximum daily dose should be limited to 2 g
- Enzyme-inducing drugs: Rifampicin, carbamazepine, phenytoin, and phenobarbital increase NAPQI production
- Repeated supratherapeutic dosing: "Staggered overdose" is more dangerous than often appreciated and can cause severe liver injury
Overdose and NAC Treatment
Paracetamol overdose is the most common cause of acute liver failure in the Western world. The Rumack-Matthew nomogram guides treatment decisions based on serum paracetamol levels plotted against time since ingestion.
| Ingested Amount | Risk Level | Action |
|---|---|---|
| < 75 mg/kg | Low risk | Observation; unlikely to cause toxicity |
| 75 – 150 mg/kg | Possible toxicity | Check serum level at 4 hours; treat per nomogram |
| > 150 mg/kg | High risk | Commence NAC treatment; check levels; consider GI decontamination if <1 hour |
| > 300 mg/kg | Very high risk | Immediate NAC; ICU monitoring; consider King's College criteria |
N-Acetylcysteine (NAC) is the specific antidote for paracetamol poisoning. It works by replenishing glutathione stores, enhancing sulfate conjugation, and directly binding NAPQI. NAC is most effective when given within 8 hours of ingestion but provides benefit even in late presentation. The standard IV protocol is a 21-hour infusion (sometimes extended), and oral NAC (72-hour protocol) is an alternative.
Worked Example
A 4-year-old child weighing 18 kg presents with fever. The available formulation is paracetamol syrup 120 mg/5 mL.
Give 11.25 mL (approximately 11 mL) of 120 mg/5 mL syrup. Maximum single dose: 20 × 18 = 360 mg (15 mL). Maximum daily: 75 × 18 = 1350 mg. Repeat every 4-6 hours as needed, maximum 4 doses in 24 hours.
Frequently Asked Questions
Can I alternate paracetamol with ibuprofen?
Yes, alternating paracetamol and ibuprofen is a common practice for managing fever or pain in children and adults. This approach can provide more consistent symptom relief than either drug alone. The typical schedule is to alternate every 3 hours (e.g., paracetamol at 0 and 6 hours, ibuprofen at 3 and 9 hours). However, this increases the risk of dosing errors, so careful tracking of timing and doses is essential.
Is paracetamol safe in pregnancy?
Paracetamol has long been considered the safest analgesic and antipyretic during pregnancy and is not associated with teratogenic effects at recommended doses. It is preferred over NSAIDs, which carry risks of premature closure of the ductus arteriosus, particularly in the third trimester. However, like all medications in pregnancy, it should be used at the lowest effective dose for the shortest duration necessary.
What is the difference between paracetamol and acetaminophen?
They are the same medication. "Paracetamol" (from para-acetylaminophenol) is the International Nonproprietary Name (INN) used in most countries. "Acetaminophen" (from N-acetyl-para-aminophenol) is the United States Adopted Name (USAN) used primarily in North America and Japan. The most well-known brand name is Tylenol.
Should I dose paracetamol by age or weight in children?
Always dose by weight when possible. Age-based dosing charts provide rough ranges but can be significantly inaccurate for children who are larger or smaller than average for their age. Weight-based dosing (15 mg/kg) ensures accurate dosing regardless of the child's size.
Can paracetamol be taken on an empty stomach?
Yes. Unlike NSAIDs, paracetamol does not cause significant gastric irritation and can be taken without food. Taking it without food may allow faster absorption and onset of action. However, if nausea is a concern, taking it with a small amount of food is acceptable without significantly affecting absorption.