Acetaminophen Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Acetaminophen possesses analgesic and antipyretic activities with few anti-inflammatory effects. It has the same effectiveness as aspirin in inhibiting brain prostaglandin synthetase but very little activity as a peripheral prostaglandin inhibitor. This difference from aspirin and other NSAIDs might explain its relative lack of effectiveness as an anti-inflammatory, antirheumatic agent. Acetaminophen does not inhibit normal platelet action, prothrombin activity, or adversely affect GI mucosal health.
Administration and Adult Dosage	For pain or fever: - Oral (PO, non-SR): 325–1000 mg every 4–6 hr, to a maximum of 4 g/day - Oral (SR Tab): 1300 mg every 8 hr - Rectal (PR): 650 mg every 4–6 hr, to a maximum of 4 g/day
Special Populations - Pediatric Dosage	For pain or fever: - Oral (PO): 10–15 mg/kg every 4–8 hr, not to exceed 5 doses per day; or by age: • Up to 3 months: 40 mg/dose • 4–11 months: 80 mg/dose • 12–23 months: 120 mg/dose • 2–3 yr: 160 mg/dose • 4–5 yr: 240 mg/dose • 6–8 yr: 320 mg/dose • 9–10 yr: 400 mg/dose • 11 yr: 480 mg/dose • 12–14 yr: 640 mg/dose • >14 yr: 650 mg/dose - Rectal (PR): • 3–11 months: 80 mg every 6 hr • 1–3 yr: 80 mg every 4 hr • 3–6 yr: 120–125 mg every 4–6 hr, to a maximum of 720 mg/day • 6–12 yr: 325 mg every 4–6 hr, to a maximum of 2.6 g/day • >12 yr: Same as adult dosage
Special Populations - Geriatric Dosage	Same as adult dosage.
Dosage Forms	- Capsule: 325, 500 mg - Gelcap: 500 mg - Chewable Tablet: 80, 160 mg - Sustained-Release Tablet: 650 mg - Tablet: 160, 325, 500, 650 mg - Drops: 48, 100 mg/mL - Elixir: 16, 24, 26, 32, 65 mg/mL - Syrup: 32 mg/mL - Suppository: 80, 120, 125, 300, 325, 650 mg
Patient Instructions	- Do not exceed the maximum recommended daily dosage of 4 g (2 g in alcoholics) - Report unresponsive fever or continued pain persisting for more than 3–5 days to your physician - Do not use with other anti-inflammatory agents unless directed by your physician
Missed Doses	- If taken on a regular schedule, take a missed dose as soon as remembered - If it is near the time for the next dose, take that dose only; do not double the dose or take extra
Pharmacokinetics - Serum Levels	- Analgesia, antipyresis: 10–20 mg/L (66–132 µmol/L) - Toxicity (acute overdose): • >300 mg/L (2 mmol/L) at 4 hr or 45 mg/L (300 µmol/L) at 12 hr: Associated with severe hepatic damage • <120 mg/L (800 µmol/L) at 4 hr or 30 mg/L (200 µmol/L) at 12 hr: Toxicity unlikely
Pharmacokinetics - Fate	- Rapid absorption from the GI tract, with peak plasma concentrations in 0.5–2 hr; liquid preparations absorbed more rapidly - Protein Binding: Unbound at therapeutic doses; 20–50% bound in overdose - Metabolism: Extensively metabolized in the liver to inactive conjugates of glucuronic and sulfuric acids and cysteine (saturable) and to a hepatotoxic intermediate metabolite (first-order) by CYP1A2 and CYP2E1; intermediate detoxified by glutathione (saturable) - Distribution: Vd = 0.95 ± 0.12 L/kg - Clearance: Cl = 0.3 ± 0.084 L/hr/kg; decreased in hepatitis, increased in hyperthyroidism, pregnancy, and obesity - Excretion: 2–3% excreted unchanged in urine
Pharmacokinetics - t¹⁄₂	- Elimination half-life: 2 ± 0.5 hr; decreased in hyperthyroidism and pregnancy, increased in hepatitis and neonates
Adverse Reactions & Side Effects	- Nontoxic at therapeutic doses - Acute overdose (≥10 g or 7.5–10 g daily for 1–2 days): Potentially fatal hepatic necrosis, possible renal tubular necrosis; hepatotoxicity may be delayed for several days - Long-term overuse: Toxic hepatitis with 5–8 g/day for weeks or 3–4 g/day for a year - Occasional: Maculopapular rash, urticarial skin reactions - Rare: Methemoglobinemia, neutropenia, thrombocytopenic purpura - Chronic use: Analgesic nephropathy with 1–15.3 kg consumed over 3–23 yr
Contraindications	- G6PD deficiency
Precautions & Warnings	- Use with caution in chronic alcoholics (not to exceed 2 g/day) and patients with phenylalanine hydroxylase deficiency (phenylketonuria) or G6PD deficiency - Some formulations contain aspartame, metabolized to phenylalanine; avoid in phenylketonuria - Some products contain sulfites
Drug Interactions	- Chronic alcoholics may have increased risk of hepatic toxicity - Long-term use of enzyme inducers (e.g., barbiturates, carbamazepine, phenytoin, rifampin, sulfinpyrazone) increases hepatotoxicity risk and may decrease efficacy - Co-administration with isoniazid increases hepatotoxicity risk; avoid acetaminophen in persons on isoniazid - Acetaminophen may increase anticoagulant effect of warfarin; monitor INR closely with long-term use
Class and Drug Brand Name	- Class: Analgesic and Anti-Inflammatory Drugs - Brand Name: Various
Notes	- Overdose Management: • Induce emesis and/or perform gastric lavage if within a few hours of ingestion • Provide supportive measures (respiratory support, fluid/electrolyte therapy) • Avoid activated charcoal as it interferes with acetylcysteine absorption • For toxic levels, administer acetylcysteine: 140 mg/kg diluted 1:3 in a soft drink or water, followed by 70 mg/kg every 4 hr for 17 doses; effective if given within 8–16 hr, indicated up to 24–36 hr post-ingestion - For short-term treatment of knee osteoarthritis, acetaminophen 2.6 and 4 g/day are comparable to naproxen 750 mg/day and ibuprofen 1.2–2.4 g/day, respectively

References

Hand of Clinical Drug Data