Bedside Snapshot

Use It For: APAP level on or above the 150 treatment line; likely toxic ingestion with level pending or unknown time; repeated supratherapeutic ingestion; acetaminophen-induced liver failure
Adult Dose: Two-bag: 200 mg/kg IV over 4 hr, then 100 mg/kg over 16 hr
Three-bag: 150 mg/kg over 1 hr, 50 mg/kg over 4 hr, 100 mg/kg over 16 hr
High-risk: bag 2 doubled to 200 mg/kg over 16 hr (over 2× line, or 30 g+ modified-release)
Pediatric Dose: Same mg/kg (labeled from 5 kg). 40 kg or less: three-bag only, with reduced volumes (3, 7, 14 mL/kg up to 20 kg) to prevent hyponatremia
Onset / Duration: IV: immediate / protects only while infusing (T½ 5.6 hr). Most effective started within 8 hr of ingestion; still give it late. PO: every 4 hr dosing
Do Not Give / Hold If: Previous hypersensitivity reaction to NAC (label; a prior anaphylactoid reaction is not a contraindication in a new overdose: call the poison center). Stop for angioedema, bronchospasm, hypotension
Watch For: Anaphylactoid reaction during the load (urticaria, wheeze, hypotension); vomiting with PO; fluid overload and low Na⁺ in children; bag-sequence and 10× errors
Reversal / Rescue: Mild reaction: pause, antihistamine, restart; wheeze, angioedema or hypotension: stop, IM epinephrine. Antidote failing: continue past 21 hr, toxicologist, transplant consult. Dialysis (massive level): raise NAC rate
Must Remember: Do not stop automatically at 20–21 hr. Keep the final-bag rate (6.25 mg/kg/hr standard; never step down a high-dose or dialysis rate) until APAP <10 mcg/mL, ALT/AST baseline or down 25–50%, INR <2.0, labs improving

Indications

ED / ICU / Transport

Acute APAP overdose: an APAP level on or above the treatment line of the revised Rumack-Matthew nomogram (150 mcg/mL at 4 hr). Draw it 4–24 hr after a single or staggered ingestion
Staggered ingestion (doses over more than 2 hr): plot from the earliest ingestion time. Start if either level sits above the line. Start too if more than 8 hr have passed since the first dose with no level (ANZ 2020: weak, very low evidence)
Likely toxic ingestion, level pending: start early when the reported dose is over 200 mg/kg or 10 g and waiting would carry you past 8 hr after ingestion
Unknown ingestion time: start now. Levels and AST/ALT decide when to stop
Presentation over 24 hr after ingestion with signs of toxicity, including rising AST/ALT: start while the results are still pending
Repeated supratherapeutic ingestion: APAP above 20 mcg/mL or abnormal AST/ALT. The nomogram does not apply here
Extended-release product: treat if any level is on or above the line. A level drawn 4–12 hr after ingestion that sits above 10 mcg/mL but below the line: repeat it. Label: 8–10 hr; consensus: 4–6 hr after the first level
Anticholinergic or opioid co-ingestion: effects present, and a level above 10 mcg/mL but below the line: repeat it 4–6 hr later
IV acetaminophen dosing error (see IV acetaminophen): the nomogram is not validated for IV exposure. Under age 6, call a poison center after a single IV dose of 90 mg/kg or more, or over 150 mg/kg in 24 hr
Acetaminophen-induced acute liver failure: give NAC even when APAP is undetectable. Late treatment still improved outcome
Pregnancy: the same thresholds and treatment apply as for non-pregnant patients

Other Uses

Non-acetaminophen acute liver failure in adults: IV NAC under hepatology direction. In the main trial, the benefit showed up only in early (coma grade I–II) encephalopathy. This use is off-label. Not recommended in children
Thick airway mucus: nebulized or instilled as an adjunct. Think chronic bronchopulmonary disease, cystic fibrosis, tracheostomy care and mucus plugging. Labeled for inhalation use

Dosing & Administration

Available Forms

IV (Acetadote and generics): 200 mg/mL (20%) in a 30 mL (6 g) vial. It must be diluted before use. Hospital stock: EMS does not usually carry it.
Inhalation or oral solution: 10% (100 mg/mL) and 20% (200 mg/mL), 30 mL vials. Not for injection.

Adult Dosing

Indication	Dose & Route	Repeat / Max	Notes
APAP overdose: two-bag IV (41 kg and up)	Bag 1: 200 mg/kg IV over 4 hr, then bag 2: 100 mg/kg IV over 16 hr	Total 300 mg/kg in 20 hr; dosing weight capped at 100 kg (20,000 mg, then 10,000 mg)	Label regimen (2024). ANZ 2020 recommends it (strong, low evidence). Label volumes 1,000 mL, then 500 mL. Fewer reactions than three-bag; the label says equivalence for preventing liver injury is not established.
APAP overdose: three-bag IV	Bag 1: 150 mg/kg IV over 1 hr; bag 2: 50 mg/kg over 4 hr; bag 3: 100 mg/kg over 16 hr	300 mg/kg in 21 hr; dosing weight capped at 100 kg (15,000 mg, 5,000 mg, 10,000 mg)	Label volumes (41 kg and up): 200 mL, 500 mL, 1,000 mL. Never infuse the load over less than 1 hr. The label suggests it for early severe liver injury or a large ingestion.
High-risk ingestion: APAP above 2 times the treatment line, or 30 g or more, or 500 mg/kg or more, of modified-release product	Bag 2 doubled: 200 mg/kg IV over 16 hr (12.5 mg/kg/hr), after the standard bag 1 (200 mg/kg over 4 hr)	Total 400 mg/kg in 20 hr; dosing weight capped at 100 kg	APAP above 2 times the line is above 300 mcg/mL at 4 hr (ANZ 2020; strong, low evidence). At 3 times the line or more, higher doses may be needed: discuss with a toxicologist or poison center. ACMT 2026 agrees a double or triple dose may be appropriate after massive overdose. Differs from FDA label: the label has no increased-dose regimen.
Continued therapy (stopping criteria not met)	Continue at 6.25 mg/kg/hr (the final bag rate, 100 mg/kg per 16 hr). On the increased-dose regimen or during hemodialysis, keep the higher rate; never step down	No fixed max: continue until all stopping criteria are met	Stopping criteria in Monitoring. Standard course: 300 mg/kg IV in 20–21 hr.
During hemodialysis	IV at 12.5 mg/kg/hr or more while dialysis runs	Minimum 12.5 mg/kg/hr during dialysis; no fixed max	Hemodialysis is recommended for APAP 900 mcg/mL or more with acidosis or altered consciousness. Oral NAC needs no adjustment.
APAP overdose: oral regimen	140 mg/kg PO load, then 70 mg/kg PO every 4 hr for 17 doses	Repeat any dose vomited within 1 hr; labeled course 72 hr; dosing weight capped at 100 kg (14 g load, 7 g maintenance)	Use when IV is unavailable or not tolerated. ACMT 2026 accepts shorter oral courses once stopping criteria are met.
Repeated supratherapeutic ingestion	Same IV regimen as acute overdose	Continue until stopping criteria are met	Treat if APAP is above 20 mcg/mL or AST/ALT is abnormal. Ask the poison center for duration.
Mucolytic (nebulized)	3–5 mL of 20% or 6–10 mL of 10% INH (nebulized), 3–4 times daily	Label range 1–10 mL of 20% (2–20 mL of 10%) every 2–6 hr	Tracheostomy instillation: 1–2 mL of 10–20% every 1–4 hr. Stop if bronchospasm progresses.

Pediatric Dosing

Indication	Dose (per kg) & Route	Max Single / Max Total	Notes
APAP overdose, 5–20 kg (three-bag IV)	150 mg/kg IV in 3 mL/kg over 1 hr; 50 mg/kg in 7 mL/kg over 4 hr; 100 mg/kg in 14 mL/kg over 16 hr	300 mg/kg in 21 hr; continue until stopping criteria are met	Three-bag only. Under 5 kg not studied: poison center or toxicologist. Keep final osmolarity at 150 mOsm/L or more.
APAP overdose, 21–40 kg (three-bag IV)	Same mg/kg doses in 100 mL, 250 mL and 500 mL	300 mg/kg in 21 hr; continue until stopping criteria are met	Reduced volumes prevent fluid overload and hyponatremia.
APAP overdose, 41 kg and up	Adult two-bag or three-bag regimen	150 mg/kg (max 15 g) load in the three-bag regimen; dosing weight capped at 100 kg	Same volumes as adults.
APAP overdose, oral	140 mg/kg PO load, then 70 mg/kg PO every 4 hr for 17 doses	Repeat any dose vomited within 1 hr; adult maximums apply	Under 20 kg: add 3 mL of diluent to each mL of 20% solution (5%).
Non-APAP acute liver failure	Not recommended in children	—	Pediatric trial: no survival benefit and lower 1-year transplant-free survival with NAC, especially under 2 yr.

Check every weight-based dose against pediatric weight-based dosing.

Preparation & Administration

Dilution (IV): the vial is hyperosmolar, so dilute it in 0.45% sodium chloride (preferred), D5W or sterile water for injection. Sterile water runs hypotonic at low concentrations. In children, keep osmolarity at 150 mOsm/L or more and confirm the diluent with pharmacy.
Rate and pump: The three-bag load runs over 1 hr. The two-bag first bag runs over 4 hr. Put each bag on a pump, labeled with its sequence and mg/kg/hr rate.
Oral: mix the 20% solution with 3 parts diet soft drink to make 5% (water by gastric tube), and use it within 1 hr. Vomiting that keeps coming: switch to IV.
Nebulizer: glass, plastic or stainless-steel parts only. Iron, copper and rubber react with NAC. Never use a heated chamber. An opened vial goes in the fridge and gets used within 96 hr.

Dosing Notes:

The rate for each bag: 150 mg/kg across 1 hr = 150 mg/kg/hr; 200 mg/kg across 4 hr = 50 mg/kg/hr; 50 mg/kg across 4 hr = 12.5 mg/kg/hr; 100 mg/kg across 16 hr = 6.25 mg/kg/hr.
ACMT 2026 backs individualizing regimens with a toxicologist. It did not evaluate shortened regimens (SNAP, SARPO). Confirm the regimen and rate at handoff.

Contraindications & Precautions

Contraindications

IV: previous hypersensitivity to acetylcysteine (labeled). A prior anaphylactoid reaction does not count as a contraindication in a later overdose (2023 consensus). Change the rate or route with poison center input.
Oral: none per label. Inhaled: known sensitivity.

Precautions

Asthma: watch closely from the start. Inhaled NAC can cause bronchospasm without warning.
40 kg or less, or fluid restriction: fluid overload drives hyponatremia, seizures and death. Use the reduced label volumes.
Alcohol use, malnutrition, fasting, CYP2E1 inducers (e.g. isoniazid): they may raise susceptibility. Even so, the 2023 consensus and ANZ 2020 do not lower the 150 line. Take borderline cases to a toxicologist.
Oral route: it makes vomiting worse. Consider an antiemetic. Weigh upper-GI bleeding (varices, peptic ulcer) against hepatotoxicity.
Inhaled or instilled: secretions may increase in volume. Have suction ready.
Hepatic encephalopathy: the 2018 oral label says to stop NAC. Current practice keeps IV NAC running in acetaminophen-induced liver failure, where it improves survival.

Hold / Reassess If

Flushing alone: keep infusing and observe.
Urticaria or pruritus without respiratory or circulatory signs: pause, give an antihistamine, restart once resolved.
Wheeze, angioedema, hypotension or anaphylaxis: stop and treat as anaphylaxis. If it returns on restart, call a toxicologist or poison center about an alternative rate or route (e.g. oral NAC). Do not leave a patient who still meets criteria untreated.
Falling Na⁺, edema or seizure in a small child: stop extra volume and review dilution with pharmacy.

Adverse Effects & Toxicity

Common

IV anaphylactoid reactions: 8% of adults and 10% of children in a large Canadian series; 14–18% in a loading-rate trial; most of them come during the load. They are less frequent at higher acetaminophen concentrations.
Two-bag vs three-bag: reactions in 1–5% vs 7–16% in three non-US cohorts (19% vs 23% at one US hospital)
Urticaria or flushing: 6.1% adults, 7.6% children; pruritus: about 4%; respiratory symptoms: about 2%
Nausea and vomiting: 10–15% within 2 hr of an IV load; common with oral NAC
Inhaled: stomatitis, nausea, rhinorrhea, chest tightness, disagreeable odor

Serious / Life-Threatening

Effect	Recognition	Management
Anaphylaxis (0.1% adults, 0.2% children; deaths reported)	Hypotension, angioedema, bronchospasm, respiratory distress, usually during the load	Stop the infusion; IM epinephrine, airway support, IV fluids; restart only after resolution and with expert input
Bronchospasm	Wheeze, chest tightness; asthma or inhaled NAC	Albuterol; during IV NAC, stop and treat as anaphylaxis
Fluid overload and hyponatremia	Falling Na⁺, edema, seizure; children 40 kg or less	Stop extra volume, check Na⁺, use label volumes, treat seizures
NAC overdose (dosing error, e.g. repeated or 10× load)	Anaphylaxis; cerebral edema; hemolytic-uremic syndrome (hemolysis, low platelets, kidney injury)	Stop NAC, supportive care, call the poison center (1-800-222-1222)

Overdose & Toxicity Management

NAC overdose: stop and manage as above. There is no specific antidote. Ask the poison center whether hemodialysis is indicated. Dialysis removal of NAC has been reported only outside NAC overdose.
Antidote failing (rising AST/ALT, persistent APAP, rising INR): keep NAC running past 21 hr at the final-bag rate, and keep any higher or dialysis rate.
Massive ingestion with acidosis or altered consciousness: hemodialysis for APAP 900 mcg/mL or more, with NAC at a higher rate. Fomepizole only with a toxicologist. The data are insufficient for a standard recommendation.
Liver transplant consult: progressive AST/ALT rise with coagulopathy, or encephalopathy despite NAC.

Monitoring

Parameter	When / How Often	Target / Act If
Clinical: vital signs, skin, breathing	Closely through the loading bag, then routinely	Itch alone: pause and treat; wheeze, angioedema or hypotension: stop, treat anaphylaxis
Clinical: mental status	Every assessment	New confusion: check glucose, blood gas, lactate and INR; involve toxicology and a transplant center
Laboratory: APAP level	4 hr or more after ingestion, and repeated as in Indications (extended-release, co-ingestion); repeat before stopping	On or above the treatment line: full course; 10 mcg/mL or more at the planned end: continue
Laboratory: ALT / AST	Baseline, before stopping, then trend	Rising, or neither at baseline nor down 25–50% from peak: continue NAC
Laboratory: INR	Baseline, when AST/ALT is elevated, and before stopping	2.0 or more: continue; rising INR with encephalopathy: transplant center
Laboratory: creatinine, BUN, glucose, electrolytes, bilirubin	Baseline and through treatment	Hypoglycemia: treat; falling Na⁺ in a child: review volumes
Laboratory: pH, lactate, phosphate	If AST/ALT is elevated, the patient is ill, or ingestion is massive	Worsening values: poor prognosis; continue NAC, consult toxicology and transplant
Laboratory: pregnancy test	Everyone who could be pregnant	Positive: same treatment; involve obstetrics
Stopping criteria: ACMT 2026 (all four strongly recommended)	Before the final bag ends, and at each check during extended therapy	Stop only when all are met: APAP <10 mcg/mL; ALT/AST at the patient's baseline or, if elevated, down 25–50% from peak; INR <2.0; creatinine, lactate, pH and phosphate improving

Interactions & Compatibility

Clinically Significant Interactions

Drug / Class	Effect	What To Do
Activated charcoal	Adsorbs oral NAC (oral solution label, 2018)	Give single-dose charcoal for a potentially liver-toxic ingestion unless the airway is unprotected (consensus: 50–100 g adults, 25–50 g children). IV NAC avoids the interaction
Hemodialysis	Removes NAC	IV NAC at 12.5 mg/kg/hr or more during dialysis; no change for oral NAC
Nebulized antibiotics (tetracyclines, erythromycin lactobionate, ampicillin, amphotericin B)	Incompatible with NAC solution	Give from separate solutions; never one nebulizer
Hydrogen peroxide, iodized oil, trypsin, chymotrypsin	Incompatible with NAC solution	Do not mix

IV Compatibility

Diluents: 0.45% sodium chloride (preferred), D5W, sterile water for injection. The vial carries about 30 mg/mL sodium. 0.45% sodium chloride adds about 1,770 mg per liter.
Y-site: the label gives no data. Run NAC on its own line where possible.
Check an institutional compatibility resource.

Special Populations

Pediatrics: labeled for children 5 kg and up. At 40 kg or less, use only the three-bag regimen with reduced volumes, because of hyponatremia risk. Doses: Pediatric Dosing table.
Neonates: dosing under 5 kg has not been studied. Involve a poison center or toxicologist.
Pregnancy: APAP and NAC both cross the placenta. Human data are thin. Animal studies at similar doses showed no fetal harm. Waiting to treat raises risk for mother and fetus, so use the standard thresholds and regimens.
Lactation: there are no data on NAC in human milk. The label says the patient may consider pumping and discarding milk for 30 hr.
Older Adults: no specific adjustment is established.
Renal Impairment: renal clearance is about 30% of the total, and the label has no adjustment. Dialysis removes NAC, so run IV NAC at 12.5 mg/kg/hr or more.
Hepatic Impairment: the half-life rises about 80%, and there is no adjustment. Liver injury is a reason to keep NAC going, not to stop it.
Obesity / Dosing Weight: use actual body weight, capped at 100 kg. The label has no studies of dose adjustment above 100 kg.
Asthma: bronchospasm risk is higher. Keep a bronchodilator at hand.

Field & Transport Considerations

Scope: the ED starts it. Critical-care transport crews and RNs keep the infusion running in transfer. Varies by state and agency protocol.
Prehospital Priorities: bring every container. Extended-release products matter. Record the time and amount ingested, and call the poison center (1-800-222-1222).
Storage & Stability: vials live at 20–25 °C (68–77 °F). A diluted bag holds for 24 hr at room temperature. A pink or purple tint is harmless.
Carried Concentration: never give the 200 mg/mL vial undiluted. Never reuse an opened vial for IV.
Infusions in Transport: confirm the regimen, the current bag, the start time, the mg/kg/hr rate and enough volume for the trip.
Handoff Essentials: ingestion time and product, APAP levels with draw times, charcoal, regimen and bag number, cumulative mg/kg, reactions, latest AST/ALT, INR and Na⁺.

Clinical Pearls

Twenty-one hours is not a stop order: Don't let the clock make the call. Before the last bag runs out, recheck APAP, AST/ALT and INR. In published cases, stopping on schedule while APAP was still detectable or enzymes were rising was followed by hepatotoxicity.

Flushing is not anaphylaxis: Flushing 30–60 min in often fades on its own, so keep infusing. Itch or hives alone: pause, give an antihistamine, and restart once it resolves. Wheeze, angioedema or hypotension? Stop, and treat it as anaphylaxis (IM epinephrine).

Nomogram rules (exam favorite): The nomogram covers single or staggered ingestions under 24 hr, plotted from the earliest ingestion time. The treatment line is 150 mcg/mL at 4 hr, not the original 200. It does not apply to RSI or an unknown time.

History is unreliable: When the amount or timing is in doubt, start NAC. Levels and liver tests will tell you when to stop.

Dialysis clears the antidote: Dialysis pulls NAC out with it. Raise the rate for the whole run (see Adult Dosing).

Pharmacology

Mechanism of Action

Glutathione precursor: NAC restores hepatic glutathione. It also serves as an alternate substrate, conjugating NAPQI (N-acetyl-p-benzoquinone imine), the toxic APAP metabolite. That prevents hepatocyte necrosis.
Established liver failure: mortality drops even after APAP has cleared, presumably through other mechanisms.
Mucolytic: the free sulfhydryl group opens disulfide bonds in mucoproteins, so mucus thins. Activity peaks at pH 7–9.

Pharmacokinetics

Route	Onset	Peak	Duration
IV	Immediate	During the infusion	Only while infused; levels fall with a T½ of 5.6 hr, nearly cleared by 30 hr
PO	Not well defined	Not well defined	Dosed every 4 hr
INH	Local effect in the airway	—	Dosed every 2–6 hr

Half-life: 5.6 hr after IV dosing (adults).
Metabolism: deacetylated to cysteine (a glutathione precursor) and oxidized to disulfides.
Elimination: clearance 0.11 L/hr/kg; renal clearance about 30% of total.
Protein binding / Vd: 66–87% bound; Vd 0.47 L/kg.

Names & Classification

Generic Name: Acetylcysteine (N-acetylcysteine, N-acetyl-L-cysteine, NAC)
Brand Names: Acetadote (IV); generic acetylcysteine injection; generic acetylcysteine solution 10% and 20% for inhalation or oral use (Mucomyst is the historical brand name)
Pharmacologic Class: Thiol amino-acid derivative; glutathione precursor
Therapeutic Class: Antidote (acetaminophen); mucolytic
Controlled Substance: Not controlled
ISMP High-Alert: No
Look-Alike / Sound-Alike: Product mix-up risk: 10%/20% inhalation/oral solution vials (not for injection) vs Acetadote 200 mg/mL IV vials

References

Cumberland Pharmaceuticals. (2025). Acetadote (acetylcysteine) injection, for intravenous use [prescribing information] (revised July 2025; two-bag dosing added November 2024). DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=472f158a-5ab9-4308-8e49-1116e6ea3d39
Hospira. (2018). Acetylcysteine solution, USP, 10% and 20%, for inhalation (mucolytic) or oral administration (acetaminophen antidote) [prescribing information] (label revised September 2018; DailyMed version posted May 2026). DailyMed, National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5558a5f5-e821-473b-7d8a-5d33d09f0586
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
American College of Medical Toxicology; Meadows, J., Hendrickson, R., & Stolbach, A. (2026). ACMT practice statement: Duration of intravenous acetylcysteine therapy following acetaminophen overdose (2026 update). https://www.acmt.net/wp-content/uploads/2026/01/ACMT-Duration-of-IV-NAC-STATEMENT-1_21_26.pdf
Cole, J. B., Oakland, C. L., Lee, S. C., Considine, K. A., Rudis, M. I., Swanson, A. L., & Olives, T. D. (2023). Is two better than three? A systematic review of two-bag intravenous N-acetylcysteine regimens for acetaminophen poisoning. Western Journal of Emergency Medicine, 24(6), 1131–1145. https://doi.org/10.5811/westjem.59099
Chiew, A. L., Reith, D., Pomerleau, A., Wong, A., Isoardi, K. Z., Soderstrom, J., & Buckley, N. A. (2020). Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Medical Journal of Australia, 212(4), 175–183. https://doi.org/10.5694/mja2.50428
Lee, W. M., Hynan, L. S., Rossaro, L., et al. (2009). Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology, 137(3), 856–864. https://doi.org/10.1053/j.gastro.2009.06.006
Squires, R. H., Dhawan, A., Alonso, E., et al. (2013). Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo-controlled clinical trial. Hepatology, 57(4), 1542–1549. https://doi.org/10.1002/hep.26001
Waring, W. S., Stephen, A. F., Robinson, O. D., Dow, M. A., & Pettie, J. M. (2008). Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose. Clinical Toxicology, 46(6), 496–500. https://doi.org/10.1080/15563650701864760
Harrison, P. M., Keays, R., Bray, G. P., Alexander, G. J. M., & Williams, R. (1990). Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine. The Lancet, 335(8705), 1572–1573. https://doi.org/10.1016/0140-6736(90)91388-Q

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N-Acetylcysteine (NAC)