Antidote
Acetylcysteine (Acetadote)
Also called NAC, Acetadote
Indications
- Acetaminophen poisoning, acute or from repeated supratherapeutic ingestion, to prevent or limit liver injury (IV or oral)
- Established acetaminophen liver injury, continued until the liver recovers
- Non-acetaminophen acute liver failure with grade 1–2 encephalopathy (off-label; Lee 2009)
- Mucolytic for thick secretions by nebulizer or instillation (inhalation solution)
Dosing
| Where | Dose |
|---|---|
| Reversal and antidotes | Acetylcysteine: 150 mg/kg over 1 h, then 50 mg/kg over 4 h, then 100 mg/kg over 16 h |
| Unit conversions | NaCl 0.9%: 154 mEq/L sodium; 3%: 513 mEq/L |
Mechanism of action
Acetylcysteine is deacetylated to cysteine, the rate-limiting precursor of glutathione, so it refills the hepatic glutathione that conjugates NAPQI, the reactive metabolite CYP2E1 makes from acetaminophen. As a sulfhydryl donor it can also bind NAPQI directly, and its sulfur may support the sulfation pathway that makes nontoxic acetaminophen sulfate. In established injury, antioxidant and microcirculatory effects help oxygen delivery and use. In the airway the same thiol splits mucoprotein disulfide bonds and thins mucus.
Pharmacology
- Hepatic: nearly fully protective within 8 h of an acute ingestion and still given later
- Immune: concentration-related, non-IgE histamine release (flushing, urticaria, bronchospasm), mostly during the high-rate loading dose
- Hematologic: lowers factors II, VII, IX and X, raising PT and INR 15–30% without liver injury (Nazar 2025)
- Respiratory: the inhaled aerosol can trigger bronchospasm, especially in asthma
- GI: oral doses smell of sulfur and cause vomiting
- Renal: no protection against contrast nephropathy (PRESERVE 2018)
Pharmacokinetics
| Half-life | 5.6 h IV for total drug (label); about 2 h for free reduced drug (Olsson 1988) |
|---|---|
| Distribution | Vd 0.47 L/kg; water-soluble; crosses the placenta |
| Protein binding | 66–87%, much of it as disulfide bonds |
| Metabolism | Deacetylated to cysteine and built into glutathione; also forms disulfides |
| Clearance | 0.11 L/h/kg; about 30% renal |
| Elimination | Urine: 13–38% of an oral radiolabeled dose in 24 h |
| Organ failure | Liver impairment: half-life up 80%, not clinically meaningful (label) |
| Dialysis | Removed by hemodialysis; EXTRIP raises the infusion rate during it |
| Bioavailability | Oral 4–9%, but first pass delivers it to the liver |
Chemistry
- N-acetyl-L-cysteine (MW 163.2), the N-acetyl derivative of L-cysteine with a free thiol (sulfhydryl) group; a single L-enantiomer
- pKa 3.24 (carboxyl) and 9.52 (thiol): an anion at pH 7.4 with an un-ionized thiol; very water-soluble (log P about −0.7)
- Acetadote: 200 mg/mL, pH 6.0–7.5, no EDTA, about 30 mg/mL sodium; at 2,600 mOsm/L it is diluted in 0.45% NaCl (preferred), D5W or sterile water; diluted bags keep 24 h
- Turns pink or purple once punctured without losing potency
Adverse effects and cautions
In the one-pagers
- Toxidromes and AntidotesAcetaminophen and NAC: Level at 4 h or later; on or above 150 mcg/mL at 4 h: give NAC.
- Aerosol Drugs and HumidityMucoactive and bland aerosols: Acetylcysteine 20%, 3–5 mL: Thick secretions: Bronchospasm: give with albuterol
- GI Bleeding, Liver Failure and PancreatitisCirrhosis and liver failure: Acute liver failure: INR 1.5 or more plus encephalopathy in a patient without cirrhosis. Acetaminophen is the top US cause: give acetylcysteine (also helps other causes). Call a transplant center early; check glucose often; ammonia over 150–200 raises cerebral edema risk (HOB 30°, sodium 145–155).
- Acute Kidney InjuryNephrotoxins and ICU causes: IV contrast: risk overstated; IV saline for AKI or eGFR <30 (ACR–NKF 2020); NAC and bicarbonate add nothing (PRESERVE)
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Sources
- FDA label: Acetadote (2025)
- FDA label: acetylcysteine inhalation (2024)
- Olsson 1988 (kinetics)
- Nazar 2025 (PT and INR)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.