Acetaminophen (Paracetamol)

Analgesic and antipyretic...

• Mechanism of action ― Acts on hypothalamus to produce antipyresis. May work peripherally to block pain impulse generation; may also inhibit prostaglandin synthesis in CNS.
• Available products ― Suppositories (Cetal), Oral (Panadol, Adol, Novaldol), Injection (Perfalgan, Injectamol)

• Mild to moderate pain and pyrexia.
• For adult.
• Orally: 0.5–1 g orally every 4–6 hours; maximum 4 g per day.
• By intravenous infusion: 15 mg/kg or 1 g every 4–6 hours, dose to be administered over 15 minutes; maximum 60 mg/kg or 4 g per day.
• By rectum: 0.5–1 g every 4–6 hours; maximum 4 g per day.
• If patients with risk factors for hepatotoxicity.
• By intravenous infusion: 15 mg/kg or 1 g every 4–6 hours every 4–6 hours, dose to be administered over 15 minutes; maximum 60 mg/kg or 3 g per day.
• Pediatric dose.
• Orally.
• Child 3–5 months: 60 mg orally every 4–6 hours; maximum 4 doses per day.
• Child 6–23 months: 120 mg orally every 4–6 hours; maximum 4 doses per day.
• Child 2–17 years: 180 mg to 1 g orally every 4–6 hours; maximum 4 doses per day.
• By rectum.
• Child 3–11 months: 60–125 mg every 4–6 hours as required; maximum 4 doses per day.
• Child 1–4 years: 125–250 mg every 4–6 hours as required; maximum 4 doses per day.
• Child 5–11 years: 250–500 mg every 4–6 hours as required; maximum 4 doses per day.
• Dose adjustment.
• Hepatic impairment: max dose 2 g per day.
• Renal impairment
• In adults: increase infusion dose interval to every 6 hours if eGFR less than 30 mL/min.
• In children: increase infusion dose interval to every 6 hours if estimated glomerular filtration rate less than 30 mL/min.

• Before administering, check when paracetamol last administered and cumulative paracetamol dose over previous 24 hours; body-weight under 50 kg; chronic alcohol consumption; chronic dehydration; chronic malnutrition; hepatocellular insufficiency; long-term use (especially in those who are malnourished).
• Cautions, further information.
• Some patients may be at increased risk of experiencing toxicity at therapeutic doses, particularly those with a body-weight under 50 kg and those with risk factors for hepatotoxicity. Clinical judgement should be used to adjust the dose of oral and intravenous paracetamol in these patients.
• Co‐administration of enzyme-inducing antiepileptic medications may increase toxicity; doses should be reduced.

• Route: Oral.
• Peak: 10-60 min.
• Metabolism: Hepatic; (microsomal enzyme systems); conjugation (glucuronic/sulfuric acid). T1/2: 2-3 hr (adults).
• Excretion: urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate).

• Anorectal erythema with rectal use (common).
• Rare or very rare.
• Hypersensitivity, hypotension, leucopenia, malaise and neutropenia with intravenous use.
• Angioedema; liver injury; skin reactions with rectal use.
• Frequency not known.
• Flushing; skin reactions; tachycardia with intravenous use.
• Agranulocytosis; bronchospasm; hepatic function abnormal; rash; severe cutaneous adverse reactions (SCARs) with oral use.
• Overdose.
• Liver damage and less frequently renal damage can occur following overdose.
• Nausea and vomiting, the only early features of poisoning, usually settle within 24 hours. Persistence beyond this time, often associated with the onset of right subcostal pain and tenderness, usually indicates development of hepatic necrosis.

• With intravenous use: for intravenous infusion (Perfalgan), give in Glucose 5% or Sodium Chloride 0.9%; dilute to a concentration of not less than 1 mg/mL and use within an hour; may also be given undiluted. For children under 33 kg, use 50 mL-vial.
• Patient and carer advice: assess patient for history of liver disease or ethanol abuse (acetaminophen and any ethanol may have adverse liver effects). Ensure adult patients keep daily dose to ≤ 4 g/day.

1. Tylenol (acetaminophen) dosing, indications, interactions, adverse effects, and more. Retrieved from reference.medscape.com website: https://reference.medscape.com/drug/tylenol-acetaminophen
2. Gerriets, V. and Nappe, T.M. (2019). Acetaminophen. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK482369/