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# Drug Information Request: Acetaminophen (Paracetamol) ## Overview Acetaminophen is a non-opioid analgesic and antipyretic. It lacks significant anti-inflammatory properties and does not inhibit platelet aggregation. Its exact mechanism involves central inhibition of prostaglandin synthesis. ## Primary Indications - Management of mild to moderate pain. - Reduction of fever. ## Adult Dosing - **Oral/IV:** 325 mg to 1000 mg every 4 to 6 hours. - **Maximum Daily Dose:** 4,000 mg (4g) per 24 hours from all sources. - **Caution:** Lower limits (typically 3,000 mg/day or less) are recommended for chronic use or adults with hepatic impairment. ## Pediatric Dosing - **Oral/Rectal:** 10 to 15 mg/kg per dose every 4 to 6 hours. - **IV (Age 2 years and older):** 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours. - **Pediatric Maximum:** 75 mg/kg/day (not to exceed 4,000 mg/day). ## Dose Adjustments - **Hepatic Impairment:** Reduce total daily dose and/or increase dosing interval in patients with active liver disease or alcohol use disorder. - **Renal Impairment:** Generally 50%–75% of the standard dose interval recommended for severe renal failure (CrCl < 10 mL/min). ## Contraindications - Known hypersensitivity to acetaminophen. - Severe active liver disease or severe hepatic impairment. ## Adverse Effects - Generally well-tolerated. - Rare but severe: Hepatotoxicity (dose-dependent), serious skin reactions (Stevens-Johnson syndrome, TEN). ## Key Drug Interactions - **Warfarin:** Chronic, high-dose use may increase the International Normalized Ratio (INR). - **Hepatotoxic agents:** Concomitant use with alcohol, isoniazid, or other potentially hepatotoxic drugs increases the risk of acetaminophen-induced liver injury. - **CYP2E1 Inducers:** May increase production of the toxic metabolite NAPQI. ## Monitoring - **Liver Function Tests (LFTs):** Monitor during long-term therapy or overdose. - **Dose Tracking:** Ensure total daily intake from all combination products (e.g., opioid-acetaminophen blends) does not exceed limits. ## Clinical Pearls - NAPQI, the toxic metabolite, is neutralized by glutathione. Toxicity occurs when glutathione is depleted (e.g., overdose or malnutrition). - Acetylcysteine is the antidote for toxicity; initiate early if overdose is suspected based on the Rumack-Matthew nomogram. - Always verify the concentration of liquid formulations, as these vary significantly by product, leading to frequent pediatric dosing errors. *** **Educational Disclaimer:** This information is for educational purposes only. Always consult current institutional protocols, official package inserts, or clinical decision support tools (e.g., Lexicomp, Micromedex) before prescribing or administering any medication.