Paracetamol

# paracetamol ## Overview Paracetamol (acetaminophen) is a centrally acting analgesic and antipyretic with weak anti-inflammatory properties. It is a first-line agent for mild-to-moderate pain and fever due to its favorable safety profile when used within recommended doses. ## Primary Indications - Mild-to-moderate pain (e.g., headache, dental pain, musculoskeletal pain, postoperative pain) - Fever reduction - Often used in combination with NSAIDs or opioids for multimodal analgesia ## Adult Dosing - **Oral/Rectal:** 500–1000 mg every 4–6 hours as needed - **Maximum single dose:** 1000 mg - **Maximum daily dose:** 4000 mg (some guidelines recommend 3000 mg/day for chronic use or in at-risk patients; verify local protocol) - **Maximum frequency:** Do not exceed 5 doses in 24 hours ## Pediatric Dosing - **Weight-based (preferred):** 10–15 mg/kg/dose every 4–6 hours - **Maximum daily dose:** 60–75 mg/kg/day (not to exceed 4000 mg/day, rarely needed in children) - **Maximum doses per 24 hours:** Up to 5 doses; do not exceed 5 doses/24 hours - **Age-based alternatives** (if weight unknown): consult local formulary; typical single dosing rounds to age-appropriate amounts (e.g., 6–11 months: 60–120 mg; 1–5 years: 120–250 mg; 6–12 years: 250–500 mg) - **Rectal dosing in children:** 15–20 mg/kg/dose, with same frequency and maximum daily limits; verify exact product dosing. ## Dose Adjustments - **Hepatic impairment:** Avoid in severe liver disease; use caution in mild-to-moderate impairment with reduced dose (e.g., maximum 2–3 g/day) and prolonged interval. - **Renal impairment:** No adjustment for short-term use; in severe CKD (eGFR <30 mL/min), consider extending dosing interval to 6–8 hours. - **Elderly:** Use minimally effective dose; generally no routine adjustment but consider lower maximum daily (e.g., 3 g/day) if frailty or risk factors. - **Malnutrition/chronic alcohol use:** Reduced hepatic glutathione stores; limit maximum daily dose (2–3 g/day). ## Contraindications - Known hypersensitivity to paracetamol - Severe hepatic impairment or acute liver disease (including active alcohol use disorder with significant liver injury) - Use caution with severe glutathione deficiency (e.g., malnutrition, chronic alcoholism) ## Adverse Effects - **Rare at therapeutic doses:** Nausea, rash, hypersensitivity reactions (including angioedema) - **Overdose (acute or cumulative):** Hepatotoxicity (centrilobular necrosis); early symptoms may be absent, then nausea, vomiting, abdominal pain; liver failure can develop 24–72 hours post-ingestion - **Chronic use:** No significant GI, CV, or renal toxicity typical of NSAIDs ## Key Drug Interactions - **Warfarin:** Paracetamol (especially >2 g/day for several days) may potentiate INR; monitor INR if regular use. - **Alcohol (chronic heavy use):** Increased risk of hepatotoxicity; avoid high doses; limit to ≤3 g/day. - **Enzyme inducers** (e.g., rifampin, carbamazepine, phenytoin): May accelerate toxic metabolite formation; increase risk of liver injury at supratherapeutic doses. - **Anticoagulants (other):** Theoretical interaction; no significant effect at low-moderate doses. ## Monitoring - **Therapeutic use:** No routine monitoring required; symptom relief and adverse effect tracking. - **In overdose:** Measure serum paracetamol level at ≥4 hours post-ingestion; use Rumack-Matthew nomogram for acute ingestion (within 24 hours) to determine need for N-acetylcysteine. - **Chronic use in at-risk patients:** Consider intermittent liver function tests (ALT/AST) if high daily doses or comorbidities. ## Clinical Pearls - Paracetamol is the analgesic/antipyretic of choice in most patients with hypertension, heart failure, renal impairment, or history of peptic ulcer disease (due to lack of antiplatelet/GI/cardiorenal effects). - **Overdose antidote:** N-acetylcysteine (IV or oral) is highly effective if given within 8–10 hours; treat empirically if ingestion >150 mg/kg in adults or >200 mg/kg in children. - Maximum daily dose variability: Some guidelines reduce to 3 g/day for chronic use or in older/frail patients; always check local protocols. - Intravenous paracetamol: Dose 1 g (adults) every 6 hours; max 4 g/day. In children <10 kg: 7.5 mg/kg/dose; 10–33 kg: 15 mg/kg/dose; >33 kg: 1 g/dose. IV formulation requires monitoring for hypotension (rare). - Paracetamol is safe in pregnancy (category B) and breastfeeding. - **Practitioner caution:** Combined opioid-paracetamol products can lead to inadvertent overdose if dose limits are ignored; counsel patients about hidden sources. --- **Disclaimer:** This information is for educational purposes only. Dosing recommendations may vary based on clinical context, local protocols, and product formulations. Always verify with current prescribing information and consult a pharmacist or relevant guidelines for individual patient care.