Aceten

Approved Indications:

• Acetaminophen (Paracetamol) Overdose: Used as an antidote to prevent or reduce liver damage after acute or chronic overdose.
• Mucolytic Agent in Respiratory Disorders: Management of thick, viscous bronchial secretions in conditions such as chronic bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, and pneumonia.
• Prevention of Contrast-Induced Nephropathy (CIN): Used prophylactically in patients undergoing radiographic contrast procedures at high risk of kidney injury.
• Adjunct in Renal Protection: Sometimes used in patients with pre-existing renal impairment to mitigate nephrotoxicity.
• Adjunct in Treatment of Atelectasis: To improve mucus clearance.

Important Off-Label or Clinically Accepted Uses:

• Idiopathic Pulmonary Fibrosis (IPF): As part of combination therapy to reduce lung fibrosis progression.
• Chronic Sinusitis and Otitis Media: Used to reduce mucus viscosity.
• Psychiatric Conditions (Emerging): Investigated for glutamate modulation effects in disorders such as schizophrenia and bipolar disorder.
• Prevention of Nephrotoxicity Induced by Certain Chemotherapeutics: Limited evidence but sometimes employed.

Acetaminophen Overdose:

• Intravenous (IV) Regimen (Standard 21-hour protocol):
  Loading dose: 150 mg/kg IV over 1 hour
  Followed by: 50 mg/kg IV over 4 hours
  Then: 100 mg/kg IV over 16 hours
• Oral Regimen:
  Loading dose: 140 mg/kg orally
  Then: 70 mg/kg every 4 hours for 17 doses

Mucolytic Use:

• Oral: 600 mg once or twice daily, adjusted based on clinical response.
• Inhalation (Nebulization): 3–5 mL of 10% or 20% solution 2–3 times daily via nebulizer.

Prevention of Contrast-Induced Nephropathy:

• 600 mg orally twice daily on the day before and day of contrast administration.

Special Populations:

• Pediatrics: Dose based on weight; for mucolytic use, typically 20–70 mg/kg/day divided doses (max 600 mg/day).
• Elderly: No specific dose adjustments required; monitor renal function.
• Renal Impairment: Use with caution; no standard dose adjustment but monitor closely.
• Hepatic Impairment: Use caution; consider dose reduction in severe hepatic dysfunction.

Routes: Oral, IV, inhalation/nebulization.

Acetylcysteine acts primarily as a precursor to glutathione, a critical intracellular antioxidant. In acetaminophen overdose, it replenishes hepatic glutathione stores depleted by toxic metabolites (NAPQI), enabling detoxification and preventing hepatocellular damage. As a mucolytic, acetylcysteine breaks disulfide bonds in mucoproteins, reducing mucus viscosity and facilitating clearance from the airways. Additionally, acetylcysteine exhibits antioxidant and anti-inflammatory properties, scavenging free radicals and modulating oxidative stress pathways, contributing to tissue protection in various organ systems.

• Absorption: Oral bioavailability is low (~10%) due to significant first-pass metabolism. Peak plasma concentrations occur within 1–2 hours after oral dosing.
• Distribution: Widely distributed, including lung tissue and bronchial secretions. Volume of distribution ~0.33 L/kg.
• Metabolism: Extensively metabolized in the liver mainly via deacetylation to cysteine and further metabolites.
• Elimination: Primarily renal excretion of metabolites; elimination half-life ranges from 5.6 to 6.25 hours.
• Onset of Action: IV administration leads to rapid systemic availability; mucolytic effects in airways begin within minutes to hours depending on route.

• Pregnancy:
  Classified as FDA Pregnancy Category B. Animal studies have not demonstrated risk to the fetus; human data are limited but do not suggest increased risk. Used when clearly needed, such as in acetaminophen overdose.
• Lactation:
  Acetylcysteine is excreted into breast milk in small amounts with no reported adverse effects on the nursing infant. Considered compatible with breastfeeding.

Primary Class: Mucolytic agent / Antidote

• Subclass: Thiol-containing antioxidant; hepatoprotective agent.

• Known hypersensitivity or allergy to acetylcysteine or any excipients in the formulation.
• Use caution or avoid in patients with bronchospasm or reactive airway diseases when using inhaled forms.

• High-Risk Groups: Patients with asthma or reactive airway disease may experience bronchospasm, especially with inhaled formulations. Use with caution and monitor closely.
• Serious Risks:
• Anaphylactoid reactions have been reported with IV administration, especially rapid infusion; monitor for signs of hypersensitivity.
• Hepatic function should be monitored in overdose treatment.
• Monitoring: Liver function tests, renal function, and clinical status in overdose patients. Monitor respiratory status during nebulized administration.
• Early Signs of Severe Events: Rash, hypotension, bronchospasm, angioedema requiring immediate cessation and emergency treatment.

Common Side Effects:

• Gastrointestinal: Nausea, vomiting, abdominal discomfort.
• Respiratory (inhaled): Cough, bronchospasm, rhinorrhea.
• Dermatologic: Rash, urticaria.

Serious/Rare Side Effects:

• Anaphylactoid reactions (flushing, hypotension, bronchospasm) with IV use.
• Angioedema.
• Rare hypersensitivity reactions.
• Fever and chills during IV infusion.

• Drugs:
• May potentiate the effects of activated charcoal in overdose management.
• Theoretically may interact with nitroglycerin, causing additive vasodilation and hypotension.
• Food: No significant interactions.
• Alcohol: No direct interaction, but alcohol use increases risk of liver injury in acetaminophen toxicity, reinforcing need for antidote use.
• Enzyme Systems: No significant CYP450 involvement; metabolized mainly by conjugation and deacetylation.

• Acetaminophen Overdose: Updated FDA guidance reinforces early administration of acetylcysteine for improved outcomes and highlights risk stratification using nomograms.
• Contrast-Induced Nephropathy: Recent guidelines suggest limited benefit; acetylcysteine use is now considered optional rather than standard for CIN prevention.
• Idiopathic Pulmonary Fibrosis: Emerging evidence on combination therapy including acetylcysteine, but recent large trials showed mixed results; no change in official recommendations.
• Ongoing evaluation for psychiatric and neuroprotective roles is underway.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep vial tightly closed until use.
• Inhalation solutions: Protect from freezing.
• Reconstituted IV solutions should be used immediately or stored according to specific protocol (usually refrigerated and used within 24 hours).
• Shake well before use (oral solution).