Acetylcysteine

Mucolytic and antidote with antioxidant properties

Acetylcysteine (also N-acetylcysteine, abbreviated NAC) is a derivative of the sulphur-containing amino acid cysteine and one of the most versatile medicines in modern medicine. It is used as a mucolytic (mucus-thinning agent) in respiratory tract conditions with viscous mucus and as a life-saving antidote in poisoning with paracetamol (acetaminophen). In addition, acetylcysteine is used as an antioxidant and precursor to endogenous glutathione in intensive care medicine and nephrology. In Germany, the active ingredient is available under brand names such as ACC, Fluimucil, and numerous generics.

Acetylcysteine is available in various dosage forms: as effervescent tablets, granules, capsules, and syrup for oral ingestion, as inhalation solution for aerosol therapy, and as injection or infusion solution for intravenous use. The combination of mucolytic effect, antioxidant capacity, and antidote property makes acetylcysteine one of the most widely used medicines in the world overall.

Mechanism of Action

Mucolytic effect: Acetylcysteine contains a free thiol group (SH group) capable of cleaving disulphide bridges in the mucin molecules of bronchial mucus. Mucins are high-molecular-weight glycoproteins crosslinked by disulphide bridges, which give mucus its viscous, thick consistency. Through the reductive cleavage of these crosslinks, the mucus is liquefied and can be more easily coughed up from the respiratory tract. Acetylcysteine acts both by topical inhalation directly on the mucus and after oral and intravenous administration via the bloodstream on bronchial secretions.

Antidote in paracetamol poisoning: Paracetamol is broken down in the liver into a highly reactive metabolite (NAPQI) which, in overdose, exhausts the cellular glutathione reserves of liver cells and leads to oxidative damage and liver failure. Acetylcysteine acts here as a precursor for glutathione synthesis: it is converted to cysteine in the cell, which is then used for the re-synthesis of glutathione. Acetylcysteine thus regenerates the antioxidant capacity of hepatocytes and prevents or limits the liver-damaging effect of NAPQI.

Antioxidant and anti-inflammatory effect: As a glutathione precursor and direct thiol compound, acetylcysteine has pronounced antioxidant properties. It directly scavenges reactive oxygen species (ROS) and increases cellular glutathione concentration. This effect is the basis for numerous off-label uses and research approaches.

Indications

• Mucolytic in respiratory diseases: Acute and chronic bronchitis, COPD, cystic fibrosis, bronchiectasis; promoting mucus elimination when expectoration is difficult
• Antidote in paracetamol poisoning: Intravenous administration within 24 hours of ingestion; effective up to 36 hours after ingestion, particularly effective in the first 8 to 10 hours
• Contrast-induced nephropathy (CIN): Off-label prophylaxis before iodinated contrast medium in patients with impaired renal function (evidence contradictory)
• Intensive care medicine: Support in sepsis, acute lung failure (ARDS), hepatorenal syndrome (off-label)
• Ophthalmology: As eye drops in keratoconjunctivitis sicca (dry eyes) and corneal mucin deposits

Dosage and Application

Mucolytic oral (adults): 200 mg three to four times daily or 600 mg once daily as a sustained-release formulation. Children 2 to 6 years: 100 mg two to three times daily. Children 6 to 14 years: 200 mg twice daily or 300 mg once daily. In cystic fibrosis, higher doses (up to 900 mg/day in adults) are frequently used.

Inhalation: 3 to 5 ml of a 10 or 20 percent solution; nebulise two to three times daily.

Antidote in paracetamol poisoning (intravenous): Three-infusion regimen: first infusion 150 mg/kg body weight in 200 ml glucose 5% over 15 to 60 minutes; then 50 mg/kg body weight in 500 ml over 4 hours; then 100 mg/kg body weight in 1000 ml over 16 hours (total dose approx. 300 mg/kg in 21 hours). Newer protocols (2-bag regimen) are under discussion.

Dissolve effervescent tablets completely in water. Take sufficient fluids (at least 1.5 to 2 litres daily), as fluid intake supports the mucolytic effect. Acetylcysteine can be taken with meals; food has no significant influence on absorption.

Side Effects

Oral common: Nausea, vomiting, diarrhoea, heartburn; these gastrointestinal complaints are usually mild and subside when taken with a meal. With effervescent tablets, the sulphur odour typical of acetylcysteine may be perceived as unpleasant.

Inhalation: Bronchospasm (particularly with hyperreactive bronchial system or bronchial asthma); acetylcysteine for inhalation in asthma should therefore only be used under close monitoring and, if necessary, in combination with a bronchodilator. Cough, rhinorrhoea, and stomatitis are possible.

Intravenous use: Anaphylactoid reactions (not true allergies, but pseudo-allergic reactions) occur in up to 30 percent of patients, particularly during the first infusion: flush, urticaria, pruritus, angioedema, bronchoconstriction, tachycardia. These reactions usually resolve on interruption of the infusion and administration of antihistamines; after subsiding, the infusion can be continued more slowly.

Rare: Hypotension, seizures (at high doses), thrombocytopenia.

Interactions

Activated charcoal: In paracetamol overdose, orally given activated charcoal can reduce the absorption of orally given acetylcysteine. Intravenous acetylcysteine is therefore the preferred route of administration.

Antibiotics (amoxicillin, cephalosporins, tetracyclines, aminoglycosides): Acetylcysteine can reduce the efficacy of some antibiotics in vitro. With concurrent oral intake, oral antibiotics should be taken at separate times (at least 2 hours).

Nitroglycerin: Combination can lead to enhanced vasodilation and headache.

Cough-suppressant agents (antitussives such as codeine, dextromethorphan): Should not be taken concurrently, as antitussives inhibit coughing up the mucus liquefied by acetylcysteine. The combination makes no therapeutic sense and can lead to secretion retention.

Special Notes

Pregnancy and breastfeeding: Acetylcysteine is used during pregnancy when the benefit outweighs the risk; in paracetamol poisoning during pregnancy in particular, intravenous acetylcysteine is the treatment of choice. With topical mucolysis and oral intake for uncomplicated respiratory tract conditions, no serious concerns are known according to current knowledge; nonetheless, medical consultation should occur.

Bronchial asthma and hyperreactive bronchial system: Inhaled acetylcysteine can trigger bronchospasm. Patients with asthma should not inhale acetylcysteine or do so only under medical supervision and in combination with a bronchodilator.

Paracetamol poisoning: The earlier acetylcysteine is given, the more effective the antidote. With unclear or delayed presentation (over 8 hours after ingestion), antidote therapy should still be started immediately, as acetylcysteine can show protective effects even later.

Efficacy as a mucolytic: The clinical evidence for the benefit of acetylcysteine as a mucolytic in acute bronchitis and uncomplicated colds is limited. The active ingredient is better documented in chronic diseases with increased mucus production (COPD, cystic fibrosis).

Frequently Asked Questions

Does acetylcysteine really help with coughing?

Acetylcysteine liquefies viscous mucus and can thus facilitate expectoration. The benefit is well documented in diseases with increased viscous mucus production (e.g. COPD, cystic fibrosis). With acute bronchitis or simple colds, the evidence is less clear; however, many patients report subjective improvement.

How is acetylcysteine used in paracetamol poisoning?

In an emergency, acetylcysteine is administered intravenously as a three-phase infusion over approximately 21 hours. Immediate presentation at an emergency department after overdose is crucial, as the efficacy of the antidote decreases with increasing time since ingestion.

Is acetylcysteine the same as NAC?

Yes, NAC (N-acetylcysteine) is the scientific abbreviation for acetylcysteine. Both terms designate exactly the same active ingredient.

References

• Product information ACC akut (Hexal AG), as of 2024
• Prescott LF: Paracetamol overdosage: pharmacological considerations and clinical management. Drugs, 1983
• Acetylcysteine for paracetamol poisoning: NICE Guideline NG109, 2019
• Grandjean EM et al.: Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease. European Respiratory Journal, 2000
• Federal Institute for Drugs and Medical Devices (BfArM): Monograph Acetylcysteine