Adult: For the short-term treatment of cases: Patient weighing >33-50 kg: 15 mg/kg. Max: 60 mg/kg (not exceeding 3,000 mg) daily. Patient weighing >50 kg: 1,000 mg. Max: 4,000 mg daily. Doses are given at least 4 hourly via infusion over 15 minutes. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline). Child: Full-term neonates and children ≤10 kg: 7.5 mg/kg (Max: 30 mg/kg daily); >10-33 kg: 15 mg/kg (Max: 60 mg/kg not exceeding 2 g daily); >33-50 kg: 15 mg/kg (Max: 60 mg/kg not exceeding 3 g daily); >50 kg: Same as adult dose. Doses are given at least 4 hourly via infusion over 15 minutes. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Oral Post-immunisation pyrexia
Child: 2-4 months 60 mg as a single dose. May give a 2nd dose after 4-6 hours if needed. Max: 4 doses daily.
Oral Fever, Mild to moderate pain
Adult: 500-1,000 mg 4-6 hourly as needed. Max: 4,000 mg daily. Dosage recommendations and available products/preparations may vary among countries (refer to specific product guidelines). Child: 3-5 months 60 mg; 6-23 months 120 mg; 2-3 years 180 mg; 4-5 years 240 mg; 6-7 years 240-250 mg; 8-9 years 360-375 mg; 10-11 years 480-500 mg; 12-15 years 480-750 mg; 16-17 years 500-1,000 mg. Doses are given 4-6 hourly as needed. Max: 4 doses daily. Dosage recommendations and available products/preparations may vary among countries (refer to specific product guidelines).
Rectal Fever, Mild to moderate pain
Adult: As supp: 500-1,000 mg 4-6 hourly. Max: 4 doses daily. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline). Child: As supp: 3-11 months 60-125 mg; 1-4 years 125-250 mg; 5-11 years 250-500 mg; 12-17 years 500 mg. Doses are given 4-6 hourly if needed. Max: 4 doses daily. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Rectal Post-immunisation pyrexia
Child: 2-3 months 60 mg as a single dose. May give a 2nd dose after 4-6 hours if needed.
Special Patient Group
Patients with chronic alcoholism or malnutrition; dehydrated patients: Max: 3 g daily.
Increase dosing interval to 6 hourly.
Mild or moderate: Max: 3 g daily. Severe: Contraindicated.
May be taken with or without food.
IV: May dilute with 0.9% NaCl or 5% dextrose in water to yield a concentration of at least 1 mg/mL.
IV: Incompatible with diazepam and chlorpromazine.
Severe hepatic impairment or active liver disease (IV).
Patient with G6PD deficiency; chronic alcoholism or malnutrition. Dehydrated patient; severe hypovolaemia (IV). Renal and hepatic impairment. Children. Pregnancy and lactation.
Blood and lymphatic system disorders: Rarely, anaemia, thrombocytopenia, agranulocytosis. Cardiac disorders: Tachycardia. Gastrointestinal disorders: Nausea, vomiting; redness of rectal mucus membranes (rectal supp). General disorders and administration site conditions: Inj site reactions (e.g. pain, burning sensation), fatigue, peripheral oedema. Investigations: Increased transaminase levels, abnormal breath sounds. Metabolism and nutrition disorders: Hypokalaemia. Musculoskeletal and connective tissue disorders: Muscle spasm, trismus. Psychiatric disorders: Insomnia, anxiety. Respiratory, thoracic and mediastinal disorders: Dyspnoea; bronchospasm (in asthmatic patients sensitive to aspirin or other NSAIDs). Skin and subcutaneous tissue disorders: Rash, pruritus, erythema, urticaria. Vascular disorders: Hypotension, hypertension, flushing. Potentially Fatal: Hepatic injury (in doses higher then recommended), anaphylaxis. Rarely, serious skin reactions such as acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN).
Monitor serum paracetamol levels in patients with hepatic disease during prolonged use. Assess relief of pain or fever.
Symptoms: Abdominal pain, anorexia, nausea, vomiting, pallor, abnormalities of glucose metabolism, metabolic acidosis; liver damage may manifest 12-48 hours after the ingestion; acute renal failure with acute tubular necrosis suggested by loin pain, haematuria, and proteinuria (may develop in the absence of severe hepatic failure); cardiac arrhythmias, pancreatitis. In severe cases, hepatic failure may lead to cerebral oedema, encephalopathy, hypoglycaemia, haemorrhage, and death. Management: Symptomatic treatment. Administer activated charcoal if it is within 1 hour of the overdose. Obtain plasma paracetamol concentration at 4 hours or later following ingestion, and LFTs at baseline and repeated at 24-hour intervals. Acetylcysteine may be applicable for up to 24 hours after ingestion (most effective if given within 8 hours); if needed, IV administration of acetylcysteine may be given, following the established dosing schedule. Alternatively, oral methionine may be given if vomiting is not a problem.
Reduced rate of absorption with colestyramine. Increased absorption with metoclopramide and domperidone. Prolonged use of paracetamol may enhance the anticoagulant effect of warfarin and other coumarins, thus increasing the risk of bleeding. Concomitant use of other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes (e.g. barbiturates) may increase the risk of paracetamol toxicity. Reduced clearance with probenecid and isoniazid. Elimination half-life may be prolonged with salicylamide. Reduced bioavailability and efficacy of lamotrigine. May increase the plasma concentration of chloramphenicol and busulfan. Increased risk of high anion gap metabolic acidosis with flucloxacillin.
May increase the risk of hepatotoxicity with alcohol. Rate of absorption may be reduced when given concomitantly with food.
May result in false-positive urinary 5-hydroxyindoleacetic acid.
Description: Mechanism of Action: Paracetamol is a para-aminophenol derivative that exhibits analgesic and antipyretic actions and weak anti-inflammatory activity. The mechanism of its analgesic effect has not been fully determined but may be associated with the inhibition of prostaglandin synthesis in the CNS and to a lesser extent, through peripheral blockage of pain-impulse generation. It produces antipyresis by inhibiting the hypothalamic heat-regulating centre.
Synonym: acetaminophen. Onset: Oral: <1 hour. IV: 5-10 minutes (analgesia); within 30 minutes (antipyretic). Duration: Oral, IV: 4-6 hours (analgesia). IV: ≥6 hours (antipyretic). Pharmacokinetics: Absorption: Well absorbed following oral and rectal administration. Mainly absorbed in the small intestine with minimal absorption from the stomach. Decreased rate of absorption with food. Time to peak plasma concentration: Approx 30 minutes to 2 hours (oral); approx 2-3 hours (rectal); approx 15 minutes (IV). Distribution: Widely distributed into most body tissues except fat. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: Approx 1 L/kg. Plasma protein binding: 10-25%. Metabolism: Metabolised mainly in the liver into sulfate and glucuronide conjugates, while a small amount is metabolised by CYP2E1 to a minor hydroxylated metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is conjugated rapidly by glutathione and inactivated to non-toxic cysteine and mercapturic acid conjugates. Undergoes first-pass metabolism (oral). Excretion: Mainly via urine (60-80% as glucuronide metabolites; 20-30% as sulfate metabolites; approx 8% as cysteine and mercapturic acid metabolites; <5% as unchanged drug). Elimination half-life: Approx 1-4 hours.
Store between 20-25°C. IV inj: Do not freeze or refrigerate. Rectal supp: Store between 2-27°C. Do not freeze. Storage recommendations may vary among countries and individual products. Refer to specific product guideline.