Synonyms: Acetaminophen, Paracetamol.

Class: Analgesics

Trade Names: Adco-Namapol, Panado, Panadol, Aceta, Tylenol, Disprol, Hedex, Cetafuse (IV).

Paracetamol Indications

• Pyrexia (Fever)
• Mild to Moderate Pain

Contraindications: Severe liver impairment.

Dose and Preparation

Adults Paracetamol Dose

Preparations: tablets (Tab), capsules (Cap), extended release (XR) and Intravenous (IV) preparation.

• For fever and Mild to moderate pain: 500mg-1000mg oral (tab, cap) 4-6 hourly as required (prn). Maximum dose of paracetamol in adults is 4g in 24 hours.
• For Post-Operative Pain: for patients over 50kg, 1g IV infusion over 15 minutes. Can be repeated after every 4 hours. Maximum dose is 4g in 24 hours. For those above 33kg but below 50kg: 15mg/kg IV infusion over 15 minutes every 4 hours as required. Do not exceed total daily dose of 60mg/kg in 24 hours (or 3g).

Children Dose

Preparations: tablets (tab), capsules (cap), syrup (syr), suspension (sus), and suppository (sup).

For Pain and fever in children above 2 months:  the dose for oral (tab, syr, sus) is 15mg/kg per dose every 4-6 hours as required (prn). Depending on the formulation you have, the dose is rounded off to the nearest practical dose.

Intravenous paracetamol post-operatively is given in children above 33kg (approximately 11 years old). The dose is 15mg/kg/dose (1.5mL/kg) infused over 15min every 4 hours. Do not exceed 24 hours and dose of 60mg/kg in 24 hours.

Special Population

Pregnancy: Paracetamol is safe in pregnancy in all three trimesters. Prolonged high doses of paracetamol may have toxic effects on the fetus.

Lactation: Paracetamol can be safely used during breastfeeding. It is excreted in small amounts in breast milk.

Renal Impairment: if GFR is 10-50 mL/min, dose is 500mg given every 6 hours. When GFR<10mL/min, doses should be 8 hourly.

Hepatic Impairment: For mild to moderate hepatic impairment, maximum dose should be kept at 2g/24 hours. In severe impairment, it is contraindicated.

Side Effects

Side effects are very few and uncommon in therapeutic doses.

Rare Side Effects

• Hypersensitivity skin reaction
• Neutropenia and Thrombocytopenia
• Hepatic Impairment (in overdose)
• Renal Impairment (in overdose)
• Angioedema
• Disorientation
• Dizziness

Mechanism of Action

Paracetamol acts in the hypothalamus by exerting antipyretic effects. It also acts peripherally to inhibit pain impulse generation.

 Paracetamol in the CNS prevents prostaglandin synthesis.

Pharmacokinetics

• Oral Bioavailability: 73-93%.
• Half-life (T½) = 1-4 hours.
• Metabolism: 90-95% of paracetamol dose is conjugated in the liver.
• Transport: Only 10-25% is protein bound.
• Excretion: kidneys as glucuronide and sulphate metabolites.

Drug Interactions and Tips

Extended Release Tablets (XR) should be swallowed whole. The dose frequency is every 8 hours, and not exceeding 3.9g in adults. Do not chew or crush or open them.

Paracetamol should ideally not be used for more than 3 days to reduce risk of side effects and toxicity.

Interactions

• Metoclopramide
• Oral anticoagulants
• Alcohol
• Domperidone
• Phenytoin
• Phenobarbital
• Chloramphenicol
• Oral Contraceptives

Caution should be exercised in persons with Alcoholism problem and G6PD deficiency. No routine monitoring necessary unless there is an incident of overdose. Paracetamol antidote is N-Acetylcystein.