ACETYLCYSTEINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACETYLCYSTEINE (ACETYLCYSTEINE).
Acetylcysteine acts as a mucolytic agent by cleaving disulfide bonds in mucoproteins, reducing mucus viscosity. It also serves as a precursor to glutathione, replenishing depleted glutathione stores in acetaminophen overdose, thereby facilitating detoxification of the toxic metabolite NAPQI.
| Metabolism | Acetylcysteine undergoes hepatic metabolism; it is deacetylated to cysteine, which is then metabolized to glutathione. It also undergoes N-acetylation via NAT2 and can be converted to inorganic sulfate. |
| Excretion | Renal: 70% as metabolites (including cysteine, cystine, inorganic sulfate); 30% unchanged in feces (biliary elimination of non-absorbed drug). |
| Half-life | Terminal half-life: 5.6–6.5 hours for total N-acetylcysteine; 2.1–2.6 hours for reduced N-acetylcysteine. Increased in hepatic impairment (up to 8–10 hours). |
| Protein binding | 50–83% bound to plasma proteins (albumin), with extensive distribution into tissues. |
| Volume of Distribution | 0.33–0.47 L/kg (reflects extensive distribution into total body water and moderate tissue binding). |
| Bioavailability | Oral: 6–10% (extensive first-pass metabolism; low due to hepatic and intestinal metabolism); intravenous: 100%; inhalation: limited systemic absorption (<10% of dose). |
| Onset of Action | Oral (acetaminophen overdose): <1 hour for maximum hepatic protection; intravenous: immediate (within minutes) for hemodynamic effects; inhalation: 5–10 minutes for mucolysis. |
| Duration of Action | Oral acetaminophen overdose: hepatoprotective effect ≥4 hours post-dose (requires repeated dosing); intravenous: hemodynamic effects last 2–4 hours; inhalation: mucolysis persists 1–3 hours. |
Acetylcysteine is administered intravenously for acetaminophen overdose: 150 mg/kg in 200 mL D5W over 60 minutes, then 50 mg/kg in 500 mL D5W over 4 hours, then 100 mg/kg in 1000 mL D5W over 16 hours. For mucolytic use via nebulization: 3-5 mL of 20% solution or 6-10 mL of 10% solution, 3-4 times daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; acetylcysteine is not significantly renally eliminated. |
| Liver impairment | No specific dose adjustment for hepatic impairment; monitor for adverse effects in severe hepatic disease. |
| Pediatric use | Same weight-based IV dosing as adults for acetaminophen overdose: 150 mg/kg loading, then 50 mg/kg, then 100 mg/kg over the specified intervals. For nebulization: 3-5 mL of 20% solution or 6-10 mL of 10% solution 3-4 times daily. |
| Geriatric use | No specific dose adjustment; use standard dosing with caution due to potential for decreased hepatic function and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACETYLCYSTEINE (ACETYLCYSTEINE).
| Breastfeeding | Acetylcysteine is excreted into breast milk in low amounts; M/P ratio approximately 0.5. Considered compatible with breastfeeding. No adverse effects reported in nursing infants. |
| Teratogenic Risk | Acetylcysteine is not associated with increased risk of major malformations. Available data from case reports and retrospective studies do not indicate teratogenicity. No risk in first trimester; theoretical benefit in third trimester for meconium passage obstruction. |
| Fetal Monitoring |
■ FDA Black Box Warning
None. Acetylcysteine does not carry an FDA black box warning.
| Common Effects | Nausea Vomiting Heartburn Stomach pain Diarrhea Loss of appetite Dryness in mouth |
| Serious Effects |
["Hypersensitivity to acetylcysteine or any component of the formulation","Acute pulmonary edema (relative contraindication for IV use)"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis, particularly with IV administration","Bronchospasm in asthmatics with inhalation use","Flushing and nausea with IV dosing","Risk of overhydration with IV administration in patients with congestive heart failure or pulmonary edema","Carcinogenicity and mutagenicity: long-term studies are inconclusive"] |
| Food/Dietary | No significant food interactions. Avoid alcohol during treatment for acetaminophen overdose due to increased hepatotoxicity risk. |
Loading safety data…
| Monitor for bronchospasm in mother during intravenous administration. No specific fetal monitoring required for therapeutic doses. |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. Theoretical reduction of oxidative stress may improve outcomes in conditions like endometriosis, but no definitive evidence. |
| Clinical Pearls | Acetylcysteine is the antidote for acetaminophen overdose; administer a loading dose of 150 mg/kg IV over 60 minutes followed by 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. For mucolytic use, nebulized acetylcysteine can cause bronchospasm in asthmatics; pre-treat with a bronchodilator. Oral acetylcysteine may be used for prevention of contrast-induced nephropathy (1.2 g twice daily before and after contrast). |
| Patient Advice | Take oral acetylcysteine exactly as prescribed; do not skip doses. · Nebulized acetylcysteine may cause coughing or throat irritation; rinse mouth after use. · For acetaminophen overdose, treatment must start within 8-10 hours for best effect. · Notify your doctor if you experience wheezing, rash, or vomiting. · Store at room temperature, away from heat and moisture. |