Acetaminophen (Oral)

Emergency & Prehospital

• Mild to moderate pain: headache, musculoskeletal and minor trauma pain, dental pain, menstrual cramps
• Moderate to severe pain when the oral route is preferred: when oral is the route you want, NASEMSO's evidence-based guidance makes a conditional recommendation for oral acetaminophen or an oral NSAID.
• Fever with discomfort or added physiologic stress. It lowers the temperature. It does not treat what caused the fever.

ED / ICU / Transport

• Multimodal, opioid-sparing analgesia: scheduled baseline analgesic alongside opioids, NSAIDs or regional techniques
• Pain when NSAIDs are unsafe: cirrhosis, bleeding risk or anticoagulation, peptic ulcer disease, kidney injury, pregnancy
• Step-down from IV acetaminophen applies once the patient can swallow and absorb. Details: acetaminophen IV

Other Uses

• Osteoarthritis and chronic musculoskeletal pain: the label covers minor arthritis pain. That includes the 650 mg extended-release tablet.

Doses vary by protocol; follow local protocols and medical direction. The cited US label or NASEMSO v3.0 is the source for each figure below (see References). Every product counts against the ceilings.

Available Forms

• Tablets and caplets: 325 mg (regular strength) and 500 mg (extra strength)
• Extended-release tablets: 650 mg (8-hour arthritis product); swallow whole, never crush, chew or split
• Oral suspension: 160 mg/5 mL (32 mg/mL) children's liquid. Dose in mL with the device packed with the product. Imported or older products may differ. Read every label
• Adult extra-strength liquid: 500 mg/15 mL (33.3 mg/mL), 12 yr and older, up to 4 doses (4,000 mg)/24 hr; do not confuse with the 160 mg/5 mL children's liquid
• Rectal suppositories: 80 mg, 120 mg, 325 mg and 650 mg (adult)
• Combination products: prescription opioid combinations such as hydrocodone-acetaminophen hold up to 325 mg per tablet. Plenty of OTC cold, flu and sleep products contain it too. Every one of them counts toward the daily maximum.

Adult Dosing

Pediatric Dosing

Weight-based dose checks: pediatric weight-based dosing.

Preparation & Administration

• Before every dose: ask about acetaminophen taken in the last 24 hr, including combination opioids and cold or sleep products; add it to your dose.
• Liquid: measure in mL with an oral syringe or the product's device, never a kitchen spoon. Extended-release: swallow whole. Rectal: insert well up into the rectum.

Contraindications

• Hypersensitivity: known allergy to acetaminophen or a product ingredient, or a prior serious skin reaction (SJS, TEN, AGEP) to it
• Acute liver failure, acute hepatitis or suspected acetaminophen liver injury. For cirrhosis see Special Populations.

Precautions

• Chronic heavy alcohol use (3 or more drinks a day): the liver is at higher risk of injury. Use a reduced daily ceiling per protocol or prescriber.
• Chronic malnutrition, low body weight, dehydration: liver injury is more likely. Use weight-based ceilings.
• Hepatic impairment or active liver disease: aim for the lowest effective dose with a reduced daily total.
• Severe renal impairment (CrCl 30 mL/min or less): you may need longer intervals and a reduced daily total.
• Warfarin: regular use can push the INR up.
• Masking fever: scheduled doses can hide a fever trend in infection surveillance.

Hold / Reassess If

• Total from all sources would exceed 4,000 mg/24 hr (2,000 mg in cirrhosis; 75 mg/kg under 50 kg)
• New rash, blistering or mucosal lesions: stop; do not rechallenge
• AST or ALT rising, jaundice or new right upper quadrant pain: stop and check an acetaminophen level
• Fever over 3 days, or pain over 10 days in adults (over 5 days in children), on self-care: find the cause

Common

• Usually well tolerated at therapeutic doses. In labeled (IV) trials, nausea and vomiting were the most common reactions in adults and children
• Headache, insomnia (adults); constipation, pruritus (children)
• Asymptomatic ALT rise: consider acetaminophen in any transaminase rise you cannot explain. That holds even when the level is undetectable.

Serious / Life-Threatening

Overdose & Toxicity Management

• Presentation: early symptoms are mild or absent, and liver injury shows up 48–72 hr after ingestion. A patient who looks well is no reason to relax. Poison Control: 1-800-222-1222.
• Level: draw a serum acetaminophen level 4 hr or more after an acute ingestion, timed from the first dose of any ingestion within 24 hr; add AST/ALT and INR.
• Nomogram: start acetylcysteine for a level on or above the 150 mcg/mL treatment line at 4 hr. Above the 300 mcg/mL high-risk line, or 30 g or more ingested: discuss higher dosing with toxicology.
• Do not wait past 8 hr: if the dose was over 200 mg/kg or over 10 g and the level will not be back by 8 hr, start acetylcysteine empirically. Unknown time or unreliable history: treat.
• Repeated ingestion over more than 24 hr: the nomogram does not apply; give acetylcysteine if the level is over 20 mcg/mL or AST/ALT is abnormal.
• Extended-release ingestion: if a level drawn 4–12 hr after ingestion is above 10 mcg/mL but below the treatment line, repeat it 4–6 hr after the first. Anticholinergic or opioid co-ingestion: same repeat if those effects are present. Timing rules: the acetaminophen level page.
• Activated charcoal: consider for an acute, potentially liver-toxic ingestion with a protected airway: adults 50–100 g, children 25–50 g PO. Timing: acetylcysteine page.
• Antidote: acetylcysteine IV or PO, at least 300 mg/kg over the first 20–24 hr (dose weight capped at 100 kg), with a 150 mg/kg IV loading dose over at least 1 hr. Continue until stopping criteria are met, not for a fixed 21 hr. Volume adjustment under 41 kg and stopping criteria: acetylcysteine page.
• Children under 6 yr and pregnancy: same nomogram and acetylcysteine criteria; involve Poison Control early.
• Extracorporeal removal: hemodialysis plus acetylcysteine for a level of 900 mcg/mL or more with acidosis or altered consciousness; IV acetylcysteine at least 12.5 mg/kg/hr during hemodialysis (acetylcysteine page).

Clinically Significant Interactions

IV Compatibility

• Not applicable here. This page covers oral and rectal products. For IV use, go to acetaminophen IV.

• Pediatrics: dose by weight, using the 160 mg/5 mL liquid. The Pediatric Dosing table has every dose and ceiling. Oral OTC labels tell caregivers to ask a clinician before dosing under 2 yr. The 80 mg infant suppository label starts its doses at 6 months.
• Neonates: use it only under a neonatal protocol. FDA labeling caps the daily total at 50 mg/kg for babies born at 32 weeks gestation or more.
• Pregnancy: still first-line for pain and fever. Use the lowest effective dose for the shortest time. Untreated fever is linked to miscarriage and birth defects. It advises against NSAIDs and opioids for routine pain and fever in pregnancy. The NSAID risks are fetal kidney effects, early ductus arteriosus closure and low amniotic fluid. The opioid risk is neonatal abstinence syndrome. The Society for Maternal-Fetal Medicine's June 2026 statement finds no established causal link to autism or ADHD. On 22 Sep 2025 the FDA announced a label-change process on that question, and it says causation is not established. The July 2026 Tylenol label does not say that yet.
• Lactation: a good choice for pain and fever while breastfeeding. Milk amounts sit far below infant doses. Adverse effects in breastfed infants appear rare, though one possible infant rash has been reported.
• Older Adults: no age-specific adjustment is established. For frail, low-weight or malnourished older adults, use the 75 mg/kg/day ceiling that applies under 50 kg.
• Renal Impairment: the label gives no oral adjustment for mild to moderate impairment. At CrCl 30 mL/min or less, longer dosing intervals and a reduced daily total may be warranted.
• Hepatic Impairment: in chronic liver disease, including decompensated cirrhosis, AASLD guidance makes acetaminophen 500 mg every 6 hr (max 2,000 mg/day from all sources) the preferred first-line analgesic. Avoid systemic NSAIDs. Chronic heavy alcohol use calls for a reduced daily ceiling per protocol or prescriber. Oral OTC labels say to ask a clinician first.
• Obesity / Dosing Weight: adult doses stay fixed. The 1,000 mg/dose and 4,000 mg/day caps do not climb with weight. Under 50 kg, dose on actual body weight.

• Scope: many EMS pain and fever protocols list oral acetaminophen as a non-opioid option. When oral analgesia is preferred, NASEMSO gives a conditional recommendation for oral acetaminophen or an oral NSAID. It varies by agency protocol.
• Storage & Stability: tablets and liquid store at 20–25°C (68–77°F). Suppositories follow the product label (FeverAll pediatric is 2–27°C/35–80°F). Heat softens suppositories.
• Suspected Overdose: bring all containers; record the product, amount and time of ingestion (or that it is unknown) and whether it was extended-release. Transport even if the patient looks well.
• Handoff Essentials: time and dose given, all other acetaminophen in the last 24 hr, weight for children, and response (pain score, temperature).

Mechanism of Action

• The exact mechanism is not established. It acts mainly in the central nervous system.
• In the brain, it weakly blocks prostaglandin synthesis. Less prostaglandin means less pain signaling and a lower hypothalamic temperature set point. Peripheral COX inhibition is small. The anti-inflammatory effect is weak, and platelet aggregation is not affected.

Pharmacokinetics

Immediate-release PO starts within 1 hr, peaks between 30 min–2 hr, and lasts 4–6 hr. Extended-release PO follows its 8 hr labeled interval. Rectal (PR) onset varies, and duration is 4–6 hr. The half-life runs about 2–3 hr: 2.4 hr in adults, 2.9 hr in adolescents and 3 hr in children. Liver damage and overdose both stretch it out.

• Metabolism: most of it goes through hepatic glucuronidation and sulfation. A small fraction is oxidized, mainly by CYP2E1, into the reactive metabolite NAPQI, and glutathione detoxifies it. In overdose, conjugation saturates and glutathione runs out. NAPQI is then free to injure hepatocytes.
• Elimination: metabolites leave in the urine. More than 90% is excreted within 24 hr, and less than 5% leaves unchanged.

Generic Name

Acetaminophen (paracetamol outside the US)

Brand Names

Tylenol, FeverAll (suppositories); many store-brand generics

Pharmacologic Class

Para-aminophenol derivative; non-opioid analgesic

Therapeutic Class

Analgesic and antipyretic

Controlled Substance

Not controlled

ISMP High-Alert

No

Error-Prone Abbreviations to Avoid

APAP (may not be recognized as acetaminophen; write the full drug name)