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# Acetylcysteine
## Overview
Acetylcysteine (N-acetyl-L-cysteine) is a mucolytic agent and the specific antidote for acetaminophen (APAP) toxicity. It acts as a precursor to glutathione, replenishing hepatic stores to prevent the accumulation of the toxic metabolite NAPQI.
## Primary Indications
* **Acetaminophen Overdose:** Antidote for prevention of hepatotoxicity.
* **Mucolytic Therapy:** Adjunctive therapy for patients with abnormal/viscid mucus secretions (e.g., COPD, cystic fibrosis, pneumonia).
* **Renal Protection:** Prevention of contrast-induced nephropathy (evidence is inconsistent; clinical use is controversial).
## Adult Dosing
* **Acetaminophen Overdose (IV):** Three-bag protocol: 150 mg/kg over 60 min, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. **Note:** Always follow institutional protocols (e.g., Rumack-Matthew nomogram/FDA-approved regimen).
* **Acetaminophen Overdose (Oral):** Loading dose 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses.
* **Mucolytic (Nebulized):** 3–5 mL of 20% solution or 6–10 mL of 10% solution 3–4 times daily.
## Pediatric Dosing
* **Acetaminophen Overdose (IV/Oral):** Weight-based dosing identical to adults (150 mg/kg IV loading or 140 mg/kg oral loading). Adjust maintenance infusions based on patient body weight.
* **Mucolytic (Nebulized):** 3–5 mL of 20% solution or 6–10 mL of 10% solution 3–4 times daily.
## Dose Adjustments
* **Hepatic Impairment:** No specific adjustment required for APAP overdose; however, monitor LFTs closely.
* **Renal Impairment:** No standard adjustment for mucolytic use. For APAP overdose, maintain the standard protocol but monitor fluid status carefully, especially in patients with heart failure or fluid overload.
## Contraindications
* Hypersensitivity to acetylcysteine or any component of the formulation.
* Oral administration: History of esophageal varices or uncontrolled gastric hemorrhage (relative contraindication for oral dosing).
## Adverse Effects
* **IV/Systemic:** Anaphylactoid reactions (flushing, urticaria, angioedema, hypotension, bronchospasm), particularly during the initial 150 mg/kg infusion.
* **Inhalation:** Bronchospasm (can be severe in asthmatics), stomatitis, rhinorrhea, nausea, and vomiting.
## Key Drug Interactions
* **Inhaled Antibiotics:** Physically incompatible with certain antibiotics (e.g., tetracyclines, aminoglycosides). If co-administration is necessary, administer at least 1 hour apart.
* **Activated Charcoal:** May decrease effective oral acetylcysteine absorption; if indicated, administer charcoal 1 hour prior to oral acetylcysteine.
## Monitoring
* **For APAP Toxicity:** Serum acetaminophen levels, AST/ALT, bilirubin, prothrombin time (PT/INR), creatinine, and electrolytes.
* **For Anaphylactoid Reactions:** Monitor for flushing or hypotension during the initial IV loading dose; slow the infusion or pause as per protocol.
## Clinical Pearls
* **Managing Anaphylactoid Reactions:** Discontinue infusion and treat with antihistamines, beta-agonists, or epinephrine as needed; often, the infusion can be restarted at a slower rate once the reaction resolves.
* **Odor:** The formulation contains sulfur and has a characteristic "rotten egg" odor, which can trigger nausea.
* **Nebulization:** Always administer with a bronchodilator (e.g., albuterol) if used in patients with hyper-reactive airway disease to mitigate the risk of bronchospasm.
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**Disclaimer:** This information is for educational purposes only. Always consult current institutional protocols, the FDA-approved product labeling, or clinical decision support software (e.g., Lexicomp, Micromedex) before prescribing or administering medication.
