Bedside Snapshot

Use It For: Pain when PO is not possible; opioid-sparing multimodal analgesia (trauma, postoperative, prehospital); fever when the enteral route is unavailable
Adult Dose: ≥50 kg: 1,000 mg IV over 15 min every 6 hr or 650 mg every 4 hr (max 4,000 mg/24 hr, all sources)
<50 kg: 15 mg/kg every 6 hr (max 750 mg/dose; 75 mg/kg/24 hr)
Pediatric Dose: 2–12 yr: 15 mg/kg IV every 6 hr or 12.5 mg/kg every 4 hr (max 750 mg/dose; 75 mg/kg/24 hr). Infants: 15 mg/kg every 6 hr (max 60 mg/kg/24 hr). Neonates: 12.5 mg/kg every 6 hr (max 50 mg/kg/24 hr)
Onset / Duration: IV analgesia: 5–10 min / 4–6 hr (peak about 1 hr); IV antipyresis: within 30 min / at least 6 hr
Do Not Give / Hold If: Severe hepatic impairment or severe active liver disease; acetaminophen hypersensitivity; any acetaminophen within 4 hr (6 hr under 2 yr) or the 24-hr max already reached
Watch For: Dose errors (mg vs mL; recheck mg/kg); hypotension in critically ill patients (BP after the infusion); rash or anaphylaxis (stop); liver injury from excess total dose (ALT/AST)
Reversal / Rescue: Overdose or dosing error: level and AST/ALT, call poison center; acetylcysteine 150 mg/kg IV over 1 hr, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr
Must Remember: Count every source and hang only the dose: PO, PR, combination opioids, OTC products and earlier EMS doses count toward the daily max. Under 50 kg, withdraw the mg/kg dose; never hang the full 100 mL

Indications

Emergency & Prehospital

Moderate to severe acute pain: a non-opioid choice, or an opioid-sparing adjunct. It needs IV access first (Paramedic/RN/CCT).
Mild to moderate pain or fever when PO is not possible: vomiting, NPO before surgery, altered mental status.
Trauma or bleeding risk: it has no meaningful platelet effect. When NSAIDs are off the table, this is still an option.
Fever after a febrile seizure in a child who cannot swallow: comfort only. It won't stop a seizure, and it won't prevent one.

ED / ICU / Transport

Multimodal, opioid-sparing analgesia: trauma, rib fractures, burns, postoperative pain (FDA-labeled with opioids for moderate to severe pain)
Fever in critically ill patients: symptom relief only, and only when the enteral route is unavailable. ICU trials show no outcome benefit.
Pain or fever with NSAID contraindications: renal impairment, GI bleeding, anticoagulation, pregnancy ≥20 weeks.

Dosing & Administration

15 mg/kg IV over 15 min; max 750 mg/dose if age ≤12 yr or under 50 kg, 1,000 mg fixed if age ≥13 yr and ≥50 kg.

Available Forms

10 mg/mL, ready to use: 1,000 mg in 100 mL glass vial or flexible bag; no dilution needed
Smaller containers: 500 mg in 50 mL and 650 mg in 65 mL bags (product-specific)
Combination product: acetaminophen 1,000 mg + ibuprofen 300 mg in 100 mL (Combogesic IV), adults only. It counts toward the acetaminophen daily max, and it carries NSAID boxed warnings.
EMS / transport: where stocked, use the 1,000 mg/100 mL container. Every weight-based dose must come out of it.

Adult Dosing

Indication	Dose & Route	Repeat / Max	Notes
Pain or fever, adults and adolescents (≥13 yr) ≥50 kg	1,000 mg IV over 15 min every 6 hr, or 650 mg IV over 15 min every 4 hr	Max 1,000 mg/dose; minimum interval 4 hr; max 4,000 mg/24 hr from all sources	Fixed dose: do not scale up for weight. Same dose as PO; no conversion needed when switching routes.
Pain or fever, adults and adolescents <50 kg	15 mg/kg IV every 6 hr, or 12.5 mg/kg IV every 4 hr, over 15 min	Max 15 mg/kg (750 mg)/dose; max 75 mg/kg (3,750 mg)/24 hr from all sources	Actual body weight. Draw the dose out into a syringe or empty container; never hang the full 100 mL.
Prehospital pain or fever (NASEMSO model guideline; house dosing)	15 mg/kg IV over 15 min; age ≥13 yr and ≥50 kg: 1,000 mg fixed	Max 750 mg/dose if age ≤12 yr or under 50 kg; max 1,000 mg/dose at age ≥13 yr and ≥50 kg; not repeated in the field; minimum interval 4 hr (6 hr under 2 yr); max 75 mg/kg or 4,000 mg per 24 hr from all sources	Minor pain, or adjunct to an opioid or ketamine for moderate to severe pain. Differs from NASEMSO: NASEMSO gives max 1 g for all ages; this text uses the label's 750 mg cap (it binds only at 50 kg and above). Under 2 yr, use the Pediatric Dosing table (neonates 12.5 mg/kg). Ask what acetaminophen was already taken and when.

Pediatric Dosing

Indication	Dose (per kg) & Route	Max Single / Max Total	Notes
Children 2–12 yr: pain or fever	15 mg/kg IV every 6 hr, or 12.5 mg/kg IV every 4 hr, over 15 min	15 mg/kg (max 750 mg) / 75 mg/kg (max 3,750 mg) per 24 hr; minimum interval 4 hr	Syringe pump for doses up to 60 mL (1.5 mL/kg at 15 mg/kg). Label caps children 2–12 yr at 750 mg/dose and 3,750 mg/24 hr even at ≥50 kg.
Infants 29 days–2 yr: fever	15 mg/kg IV every 6 hr, over 15 min	15 mg/kg / 60 mg/kg per 24 hr; minimum interval 6 hr	Analgesic efficacy under 2 yr is not established (label); use for pain under 2 yr is off-label.
Neonates 0–28 days (born ≥32 wk gestation): fever	12.5 mg/kg IV every 6 hr, over 15 min	12.5 mg/kg / 50 mg/kg per 24 hr; minimum interval 6 hr	Born <32 wk: not established (NICU specialist use). UK label uses 7.5 mg/kg (max 30 mg/kg/24 hr) up to 10 kg.
Prehospital: fever after a febrile seizure (NASEMSO Seizures guideline)	15 mg/kg IV or IO over 15 min	Max 650 mg; not repeated in the field	Comfort only; does not stop or prevent seizures. IO use is off-label (EMS protocols). Neonates: 12.5 mg/kg, minimum interval 6 hr (label). Differs from the house analgesia cap (750 mg): NASEMSO Seizures guideline caps this indication at 650 mg.

Not sure of the weight? Use pediatric weight-based dosing to estimate it and check the dose. Renal and hepatic adjustments are in Special Populations.

Preparation & Administration

Infusion time: every dose runs over 15 min (label). The label does not cover a faster infusion.
Doses below the container size: withdraw the dose into a syringe or empty sterile container first. The 100 mL container is not for patients under 50 kg.
Pump: use an infusion pump for every dose. A syringe pump covers pediatric volumes up to 60 mL.
Glass vials: use a vented IV set. When it runs as the primary infusion, watch the end of the infusion for air entry.
No additives: do not add other drugs to the container or infusion device
After opening: once the glass vial is punctured or the contents are transferred, give it within 6 hr (label). Bag products have their own limits. Check the label.
Volume: each 1,000 mg is 100 mL (400 mL/day at the max). Count that volume in fluid-restricted patients. Excipients differ by product. The Sandoz 1,000 mg vial contains mannitol, so check each label.

Contraindications & Precautions

Contraindications

Known hypersensitivity to acetaminophen or any excipient in the IV product
Severe hepatic impairment or severe active liver disease

Precautions

Hepatic risk: hepatic impairment, active liver disease, chronic heavy alcohol use, chronic malnutrition, severe hypovolemia (dehydration, blood loss): reduce the daily total
Severe renal impairment: CrCl ≤30 mL/min: longer interval and lower daily total
Weight under 50 kg: small adults and adolescents need mg/kg dosing. Not 1,000 mg.
Critically ill or unstable: blood pressure falls have been reported after IV acetaminophen. Recheck the BP.
Skin reactions: stop at the first rash. AGEP, SJS and TEN are rare, but they can be fatal.

Hold / Reassess If

Any acetaminophen within the minimum interval, or the next dose would exceed the 24-hr max
New rash, urticaria, facial swelling or wheeze: stop and treat
Clinically important BP fall after a dose: treat and reassess before redosing
Rising ALT/AST or jaundice: stop and check an acetaminophen level

FDA Boxed Warning: medication errors and hepatotoxicity. Dosing errors have caused accidental overdose and death. Do not confuse mg and mL. Dose by weight under 50 kg. Program the pump correctly. Keep the total from all sources under the daily maximum. Acetaminophen can cause acute liver failure. That usually happens above the daily maximum, and often with more than one acetaminophen product.

Adverse Effects & Toxicity

Common

Nausea (34% vs 31% placebo) and vomiting (15% vs 11%) in adult trials
Headache (10%) and insomnia (7%)
Infusion site pain
Children: nausea, vomiting, constipation, pruritus (≥5%)
The antipyretic effect can hide a new fever

Serious / Life-Threatening

Effect	Recognition	Management
Hepatotoxicity / acute liver failure	Excess total dose, often from several products; early nausea and malaise; liver injury may not show for 48–72 hr	Stop; acetaminophen level, ALT/AST, INR; poison center; acetylcysteine
Dosing error overdose	mL given as mg (10-fold), full 100 mL hung for a small child, duplicate orders	Stop; calculate total mg/kg; poison center 1-800-222-1222
Hypotension	BP falls are reported after the infusion in critically ill patients; in the ASTER sepsis trial (1 g IV every 6 hr), hypotension was no more frequent than with placebo (trial abstract)	Stop the infusion if still running; give an IV fluid bolus; start a vasopressor if hypotension persists; consider another antipyretic or analgesic
Anaphylaxis / hypersensitivity	Facial or throat swelling, urticaria, respiratory distress	Stop; epinephrine IM and anaphylaxis care; do not re-expose
Serious skin reactions (AGEP, SJS, TEN)	Rash, blistering, mucosal involvement	Stop permanently; specialist care

Overdose & Toxicity Management

Signs: early on, nausea, vomiting, diaphoresis and malaise. Hepatic necrosis by 48–72 hr. Renal tubular necrosis, hypoglycemia and thrombocytopenia can follow.
IV exposure: the label's Rumack-Matthew nomogram is for an acute ingestion with a known time (Acetadote label, sections 2.1 and 2.2). An IV exposure is different. Send an acetaminophen level and AST/ALT, and call the poison center (1-800-222-1222).
Children under 6 yr: call the poison center for any IV dosing error or unintended large dose. The 2023 US/Canada consensus addresses this age group separately.
Antidote: acetylcysteine IV, same mg/kg for adults and children ≥5 kg: 150 mg/kg over 1 hr, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr; or (≥41 kg) 200 mg/kg over 4 hr, then 100 mg/kg over 16 hr. Whether the two-bag regimen works as well as the three-bag regimen is not known. With early signs of severe liver injury or a large ingestion, the label suggests the three-bag regimen. Cap the dosing weight at 100 kg. Keep going until the stopping criteria are met. After an IV dosing error, the poison center or toxicologist guides acetylcysteine use

Monitoring

Parameter	When / How Often	Target / Act If
Clinical: pain score	Baseline, 30–60 min after the dose, before each repeat	Inadequate relief: add an NSAID, opioid or ketamine rather than repeating acetaminophen early
Clinical: temperature	30–60 min after the dose, then every 4–6 hr	Fever persists or returns early: look for the source; do not shorten the interval
Clinical: BP and HR	Before, at the end of the infusion and about 30 min later in critically ill patients	Clinically important fall: treat; reassess before the next dose
Clinical: skin and airway	During and after each dose	Rash, urticaria or swelling: stop; anaphylaxis care if needed
Infusion safety: dose check	Every dose and at every handoff	Confirm weight, mg/kg, mg and mL, pump rate, and time and amount of the last dose from any source
Laboratory: ALT / AST	Baseline and periodically with hepatic risk factors or repeated dosing; at once if overdose suspected	Rising: stop acetaminophen, send a level, call the poison center
Laboratory: acetaminophen level	Suspected overdose or dosing error	Interpret with the poison center; the label's nomogram covers acute ingestion with a known time (Acetadote label, sections 2.1 and 2.2)
Laboratory: INR	Patients on warfarin receiving repeated doses	Rising INR: adjust warfarin with the prescriber

Interactions & Compatibility

Clinically Significant Interactions

Drug / Class	Effect	What To Do
Other acetaminophen products (PO, PR, hydrocodone or oxycodone combinations, OTC cold remedies, Combogesic IV)	Cumulative dose and hepatotoxicity	Count every source before each dose; do not give with Combogesic IV
CYP2E1 inducers, chronic heavy alcohol use	May increase hepatotoxic potential (clinical effect not established)	Use a reduced daily total; monitor ALT/AST
Warfarin	INR rises reported with chronic 4,000 mg/day	Check INR more often with repeated dosing
Opioids, NSAIDs (ketorolac), ketamine	Additive analgesia; opioid sparing	Combine as a multimodal regimen; monitor for each drug's own effects

IV Compatibility

Give undiluted from the container; do not add other medications to the container or infusion device.
Diazepam and chlorpromazine are physically incompatible. Do not give them at the same time.
Verify with an institutional compatibility resource.

Special Populations

Pediatrics: labeled for pain from 2 years and for fever from birth (neonates born at ≥32 weeks). Most reported IV errors are miscalculated doses in small children. Two patterns stand out: mL given as mg, and full containers. The doses are in the Pediatric Dosing table.
Neonates: 12.5 mg/kg gives exposures similar to 15 mg/kg in older children. Keep a 6-hr minimum interval. Not established for neonates born before 32 weeks.
Pregnancy: oral-use studies show no clear association with birth defects, miscarriage or adverse maternal or fetal outcomes. On September 22, 2025, FDA announced action on a possible link between prenatal use and autism or ADHD. It stated that a causal relationship has not been established. The Sandoz IV label (effective 2021) has no such wording. Use the lowest effective dose for the shortest time. Don't leave significant fever or pain untreated.
Lactation: it passes into milk. Average and maximum neonatal doses are about 1% and 2% of the weight-adjusted maternal dose (after a single oral 1 g dose). Breastfeeding can continue. One infant rash has been reported.
Older Adults: the label shows no overall differences in safety or effectiveness. Frail patients under 50 kg need mg/kg dosing.
Renal Impairment: CrCl ≤30 mL/min calls for a longer dosing interval and a lower daily total (US label). The UK label sets a 6-hr minimum interval.
Hepatic Impairment: contraindicated in severe impairment or severe active liver disease. Otherwise, cut the daily total. The UK label caps adults over 50 kg at 3,000 mg/24 hr with hepatic impairment, chronic alcohol use, chronic malnutrition or dehydration. The US label gives no number.
Obesity / Dosing Weight: ≥50 kg: fixed 1,000 mg dose regardless of weight (max 4,000 mg/day). Under 50 kg: actual body weight.

Field & Transport Considerations

Scope: Paramedic, RN and critical-care transport, where the formulary includes it. It varies by state and agency protocol.
Prehospital Role: for moderate to severe pain, the NAEMSP/NASEMSO evidence-based pain guideline suggests IV acetaminophen over IV opioids (conditional). It suggests IV NSAIDs over IV acetaminophen (conditional). The NASEMSO model guideline gives 15 mg/kg PO or IV (max 1 g) for minor pain or as an adjunct. It leaves acetaminophen out of its 5-min analgesic repeats. Here is where this page differs from NASEMSO. NASEMSO gives max 1 g for all ages. This page caps the dose at 750 mg/dose for age ≤12 yr or under 50 kg (label). Its febrile-seizure guideline caps the dose at 650 mg (PR, IV or IO). Under 2 yr, follow the label-based Pediatric Dosing table (neonates 12.5 mg/kg).
Military (TCCC): CoTCCC Guideline Change 25-03 (2025) uses a two-step model. Step 1 is a non-opioid pill pack for mission-capable casualties. The 2025 abstract names suzetrigine and does not list acetaminophen. Step 2 adds ketamine or esketamine. IV acetaminophen does not appear in the 2025 abstract.
Storage & Stability: 20–25 °C (68–77 °F). Do not refrigerate or freeze (Sandoz label). Other products may differ, including on excursion limits and light protection. Check the product label. Once opened, give it within the time limit (6 hr for the glass vial).
Infusions in Transport: a 15-min infusion on a pump or syringe pump. Vented tubing for glass vials. Start it early, so it finishes before a move or handoff.
Handoff Essentials: time and dose in mg (and mg/kg), weight used, all acetaminophen in the past 24 hr including home OTC and combination products, and the response.

Clinical Pearls

Hang the dose, not the bottle: under 50 kg? Withdraw the mg/kg dose before you start the infusion. A pump set to part of a 100 mL container, or mL read as mg, gives an infant a 10-fold overdose.

IV is faster, not stronger: does IV hit harder? No. The peak runs up to 70% higher than the same oral dose, but total exposure is similar. Use IV when the oral route is not possible. Once the gut works, switch to oral.

Prehospital analgesic choice (FP-C, CCP-C): NAEMSP/NASEMSO suggest IV acetaminophen over IV opioids. They suggest IV NSAIDs over IV acetaminophen. Both are conditional. The only strong recommendation they make: intranasal fentanyl over IV opioids for children without IV access.

Fever in the ICU (CCRN, CFRN): the ASTER sepsis trial found that 1,000 mg IV every 6 hr did not increase days free of organ support. The earlier HEAT trial (fever with suspected infection, 700 ICU patients) showed no mortality benefit. Its 90-day deaths were 15.9% vs 16.6%. So treat the fever for comfort. Don't expect it to change the outcome.

Not for ED migraine: the American Headache Society 2025 update rated IV acetaminophen likely ineffective for migraine in the ED. Reach for prochlorperazine, metoclopramide or ketorolac instead.

Nomogram limits: the revised Rumack-Matthew nomogram covers an acute ingestion with a known time. It applies when the level is available within 8 hours (Acetadote label, sections 2.1 and 2.2). The label says it does not apply to repeated supratherapeutic ingestion (section 2.6). For an IV dosing error, send a level and AST/ALT. Then let the poison center decide on acetylcysteine (2023 US/Canada consensus).

Pharmacology

Mechanism of Action

Thought to act primarily centrally (the precise mechanism is not established, per the Combogesic IV label, section 12.1). The effects are analgesia and antipyresis.
Peripheral prostaglandin inhibition: the label credits the NSAID component, ibuprofen, for this effect (Combogesic IV label, section 12.1). The prehospital guideline (ref 3) suggests IV NSAIDs over IV acetaminophen (conditional).
No significant platelet effect (single doses up to 3,000 mg; 1,000 mg every 6 hr for 48 hr) → no change in bleeding time.

Pharmacokinetics

Route	Onset	Peak	Duration
IV (analgesia)	5–10 min	About 1 hr	4–6 hr
IV (antipyresis)	Within 30 min	—	At least 6 hr

Half-life: adults 2.4 hr. Adolescents 2.9 hr. Children 3 hr. The peak level comes at the end of the 15-min infusion.
Metabolism: it is metabolized in the liver by glucuronidation and sulfation. A small fraction goes via CYP2E1 to NAPQI, which glutathione detoxifies. NAPQI builds up when glutathione runs out (overdose, malnutrition, chronic alcohol use).
Elimination: urine, mostly as conjugates; over 90% within 24 hr, under 5% unchanged.
Protein binding / Vd: 10–25% bound; Vss about 0.8 L/kg in adults, 1.2 L/kg in children.

Names & Classification

Generic Name: Acetaminophen (paracetamol outside the US), injection for IV use
Brand Names: Multiple generics. Combogesic IV (with ibuprofen)
Pharmacologic Class: Non-opioid, non-salicylate analgesic and antipyretic (para-aminophenol derivative)
Therapeutic Class: Analgesic; antipyretic
Controlled Substance: Not controlled
ISMP High-Alert: No (but carries an FDA boxed warning for dosing errors)
Look-Alike / Sound-Alike: No name pair commonly reported; the main errors are mg vs mL and weight-based dose confusion
Error-Prone Abbreviations to Avoid: APAP: write "acetaminophen"

References

Sandoz Inc. (2021). Acetaminophen injection, for intravenous use: Full prescribing information (label effective August 23, 2021; DailyMed version checked October 15, 2026). U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2884e523-5f12-48d6-98dc-3a80cde524f8
B. Braun Melsungen AG. (2025). Paracetamol 10 mg/ml solution for infusion: Summary of product characteristics (text revised April 2025). Electronic Medicines Compendium (UK). https://www.medicines.org.uk/emc/product/15148/smpc
Lindbeck, G., Shah, M. I., Braithwaite, S., Powell, J. R., Panchal, A. R., Browne, L. R., et al. (2023). Evidence-based guidelines for prehospital pain management: Recommendations. Prehospital Emergency Care, 27(2), 144–153. https://doi.org/10.1080/10903127.2021.2018073
National Association of State EMS Officials. (2022). National Model EMS Clinical Guidelines, version 3.0 (Pain Management; Shock; Seizures). https://ems.utah.gov/wp-content/uploads/sites/34/2024/05/National-Model-EMS-Clinical-Guidelines_2022.pdf
Dart, R. C., Mullins, M. E., Matoushek, T., et al. (2023). Management of acetaminophen poisoning in the US and Canada: A consensus statement. JAMA Network Open, 6(8), e2327739. https://doi.org/10.1001/jamanetworkopen.2023.27739
Cumberland Pharmaceuticals Inc. (2025). ACETADOTE (acetylcysteine) injection: Full prescribing information (DailyMed, updated July 2025). U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=472f158a-5ab9-4308-8e49-1116e6ea3d39
Ware, L. B., Files, D. C., Fowler, A., et al., for the NHLBI PETAL Clinical Trials Network. (2024). Acetaminophen for prevention and treatment of organ dysfunction in critically ill patients with sepsis: The ASTER randomized clinical trial. JAMA, 332(5), 390–400. https://pmc.ncbi.nlm.nih.gov/articles/PMC11304120/
Robblee, J., Minen, M. T., Friedman, B. W., Cortel-LeBlanc, M. A., Cortel-LeBlanc, A., & Orr, S. L. (2026). 2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache, 66(1), 53–76. https://doi.org/10.1111/head.70016
Food and Drug Administration, U.S. (2025, September 22). FDA responds to evidence of possible association between autism and acetaminophen use during pregnancy [Press release]. https://www.fda.gov/news-events/press-announcements/fda-responds-evidence-possible-association-between-autism-and-acetaminophen-use-during-pregnancy
Young, P., Saxena, M., Bellomo, R., et al. (2015). Acetaminophen for fever in critically ill patients with suspected infection (HEAT trial). New England Journal of Medicine, 373(23), 2215–2224. https://doi.org/10.1056/NEJMoa1508375
Hikma Pharmaceuticals USA Inc. (2024). COMBOGESIC IV (acetaminophen and ibuprofen) injection: Full prescribing information (label effective November 25, 2024). U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=be408a5a-48e4-43c0-9cb1-bbf830b54f5b
Barbee, G. A., et al. (2026). Analgesia in Tactical Combat Casualty Care (TCCC): TCCC Guideline Change 25-03 [Abstract]. Journal of Special Operations Medicine, 26(2), 97–111. https://doi.org/10.55460/J.Spec.Oper.Med.2026.75L9-4KVD

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