Paracetamol

Analgesic, antipyretic, non‑opioid, centrally acting, non‑steroidal (no anti‑inflammatory activity)

Paracetamol reduces pain and fever primarily by inhibiting cyclo‑oxygenase (COX‑1 and COX‑2) in the central nervous system, thereby decreasing prostaglandin synthesis. It may also act through serotonergic pathways and the endocannabinoid system, contributing to its analgesic effects. Unlike NSAIDs, paracetamol’s peripheral COX inhibition is minimal, which explains its lack of anti‑inflammatory activity and lower gastrointestinal toxicity.

Absorption: Rapid oral absorption with peak plasma concentrations within 30–60 minutes. Bioavailability is ~80 % and is not significantly affected by food. Distribution: Widely distributed in body tissues with a volume of distribution of ~0.9 L/kg. Paracetamol is not highly protein‑bound (~10 %) and can cross the blood–brain barrier and placenta. Metabolism: Primarily hepatic via conjugation (glucuronidation and sulfation) to produce inactive metabolites. A small fraction is oxidized by CYP2E1 to the toxic metabolite N‑acetyl‑p‑benzoquinone imine (NAPQI). Excretion: Metabolites are eliminated renally. The parent compound and conjugates are excreted in urine within 24 hours. Half‑life: The terminal elimination half‑life is ~2–3 hours in healthy adults but may be prolonged in hepatic impairment.

• Analgesic: reduces nociceptive pain via central COX inhibition. • Antipyretic: lowers hypothalamic set point by decreasing prostaglandin E₂. • Minimal anti‑inflammatory effect due to negligible peripheral COX activity. • No significant effect on platelet aggregation or gastrointestinal mucosa, reducing GI bleeding risk.

• Acute mild to moderate pain (headache, musculoskeletal pain, dental pain) • Fever reduction in febrile illnesses (viral or bacterial) • Osteoarthritis pain when used adjunctively with other analgesics • Post‑operative pain management to reduce opioid requirements

Absolute: • Known hypersensitivity to paracetamol or any formulation component • Severe hepatic impairment or chronic liver disease Relative: • Chronic alcohol use (increases risk of hepatotoxicity) • Pregnancy (use only if benefits outweigh risks; category B) • Severe renal impairment (dose adjustment recommended)

Adult (non‑pregnant): 500–1000 mg orally every 4–6 hours as needed, not to exceed 4000 mg/day. Adult (pregnant, trimester‑specific): 500–1000 mg orally every 6 hours; maximum 4000 mg/day unless otherwise directed by a physician. Pediatric (0.5–15 kg): 10 mg/kg orally every 4–6 hours; do not exceed 60 mg/kg/day. Pediatric (15–40 kg): 15 mg/kg orally every 4–6 hours; do not exceed 60 mg/kg/day. Note: Over‑the‑counter preparations often contain 500 mg or 325 mg tablets; dose calculations should consider total daily intake from all sources.

Pediatric: Weight‑based dosing starting at 10 mg/kg; avoid exceeding 60 mg/kg/day. Geriatric: Standard adult dosing applies; monitor for hepatic function as age‑related decline can prolong half‑life. Renal impairment: No dose adjustment needed for mild to moderate impairment; in severe CKD, monitor for signs of hepatotoxicity. Hepatic impairment: Reduce dose to 500 mg every 8 hours or use alternative antipyretic; monitor liver enzymes.

Common (>10%): • Gastrointestinal upset (nausea, mild abdominal discomfort) • Dizziness or headache (rare) Serious (<1%): • Hepatotoxicity (acute liver failure, elevated ALT/AST >10× ULN) • Hypersensitivity reactions (rash, urticaria, Stevens–Johnson syndrome) • Rare cases of aplastic anemia (extremely uncommon)

• Warfarin: Paracetamol may potentiate anticoagulant effect; monitor INR closely. • Isoniazid & Rifampin: Both drugs increase CYP2E1 activity, accelerating conversion to NAPQI; risk of hepatotoxicity rises. • Alcohol: Co‑consumption increases hepatic metabolism to NAPQI, heightening liver injury risk. • CYP2E1 inducers (e.g., phenobarbital): Increase toxic metabolite formation, raising hepatotoxicity risk.

• Hepatotoxicity: Overdose (≥4 g in 24 h) can cause fulminant hepatic failure; seek immediate medical attention if symptoms arise. • Avoid concurrent use of multiple acetaminophen‑containing products to prevent accidental overdose. • In patients with chronic liver disease or alcoholism, use the lowest effective dose for the shortest duration.

Pregnancy: Category B; animal studies have shown no teratogenic effect. Use only if benefits outweigh risks. Lactation: Paracetamol is excreted in breast milk at low levels; generally considered safe for nursing infants. Monitor infants for signs of hepatotoxicity if maternal dose is high.

• Liver function tests (ALT, AST, bilirubin) if chronic use or in patients at risk. • Complete blood count if prolonged use or in patients receiving isoniazid. • INR in patients on warfarin.

• Do not exceed the maximum daily dose of 4000 mg; check all medications for acetaminophen content. • Avoid alcohol while taking paracetamol to reduce liver injury risk. • If nausea, vomiting, or abdominal pain occurs, or if you suspect an overdose (e.g., feeling faint, jaundice), seek medical help immediately. • For children, use a pediatric dosing device; do not use adult tablets for kids.

Store at 20–25 °C in a dry place away from direct sunlight. Keep the container tightly closed. Do not use after the expiration date. For crushed tablets, store in a sealed container to avoid moisture.

• Use paracetamol as the first‑line agent for mild to moderate pain and fever, especially when NSAID contraindications exist. • When combining with opioids, aim to keep total daily acetaminophen below 4000 mg to mitigate hepatotoxicity. • In patients with chronic alcohol use, consider reducing dose or using alternative analgesics to avoid additive hepatic stress.

• Katzung BG. Basic & Clinical Pharmacology. 15th ed. McGraw‑Hill; 2017. • McCance R, Hall J. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw‑Hill; 2018. • FDA Guidance on Acetaminophen Safety and Hepatotoxicity. FDA; 2022.