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# Acetylcysteine
## Overview
Acetylcysteine (N-acetylcysteine, NAC) is an mucolytic agent that breaks disulfide bonds in mucoproteins, reducing viscosity. It also acts as an antidote to acetaminophen overdose by replenishing hepatic glutathione stores.
## Primary Indications
* Acetaminophen (APAP) overdose
* Adjunct to mucolytic therapy for respiratory conditions with excessive mucus production (e.g., cystic fibrosis, chronic obstructive pulmonary disease)
## Adult Dosing
**Acetaminophen Overdose:**
* **Intravenous (IV):** Load: 150 mg/kg infused over 60 minutes. Followed by: 50 mg/kg infused over the next 4 hours. Followed by: 100 mg/kg infused over the next 16 hours.
* Maximum dose per infusion is typically capped at 150 mg/kg/hr for the initial load and 50 mg/kg/hr for subsequent infusions. Total dose over 21 hours is approximately 300 mg/kg.
* Some protocols may use a fixed dosing regimen (e.g., 300 mg/kg total dose over 21 hours).
* **Oral (PO):** Load: 140 mg/kg. Followed by: 70 mg/kg every 4 hours for 17 doses (total of 18 doses).
* Maximum single dose typically 700 mg/kg/dose for oral route, but this is rarely reached.
**Mucolytic Therapy:**
* **Intravenous (IV):** 600 mg once daily or 300 mg twice daily. May be increased to 1200 mg once or twice daily based on clinical response.
* **Nebulized (inhaled):** 1-10 mL of a 10-20% solution every 2-6 hours. Alternatively, 3-5 mL of a 20% solution every 3-4 hours.
* **Oral (PO):** 200 mg twice daily to 600 mg three times daily.
## Pediatric Dosing
**Acetaminophen Overdose:**
* **Intravenous (IV):** Same as adult dosing (150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours). Dosing is based on weight, not age.
* **Oral (PO):** Same as adult dosing (140 mg/kg load, then 70 mg/kg every 4 hours for 17 doses).
**Mucolytic Therapy:**
* **Nebulized (inhaled):** 1-10 mL of a 10-20% solution every 2-6 hours. For younger children, smaller volumes may be used.
* **Oral (PO):** Generally 10 mg/kg/dose every 4-6 hours. Maximum 600 mg/day.
## Dose Adjustments
No specific dose adjustments are typically required for renal or hepatic impairment for the acetaminophen overdose protocol. For mucolytic use, dose adjustments may be based on clinical response and tolerability.
## Contraindications
* Hypersensitivity to acetylcysteine or any component of the formulation.
* Active bronchospasm (for nebulized formulations, use with caution and bronchodilator).
## Adverse Effects
* **IV Acetaminophen Antidote:** Anaphylactoid reactions (rash, pruritus, angioedema, bronchospasm, hypotension), nausea, vomiting.
* **Nebulized:** Bronchospasm, rhinorrhea, nausea, vomiting, stomatitis.
* **Oral:** Nausea, vomiting, diarrhea, rash.
## Key Drug Interactions
* **Activated charcoal:** Decreases absorption of oral acetylcysteine.
* **Nitroglycerin:** Potential for increased hypotensive effects.
## Monitoring
* **Acetaminophen Overdose:** Acetaminophen and salicylate levels, liver function tests (LFTs), international normalized ratio (INR), blood glucose, renal function, and clinical signs of hepatic injury.
* **Mucolytic Therapy:** Respiratory status, sputum production, and signs of bronchospasm.
## Clinical Pearls
* The IV formulation for acetaminophen overdose is preferred in patients who are vomiting or unable to tolerate oral medications.
* Anaphylactoid reactions are common with IV acetylcysteine and are often manageable with dose interruption and/or slowed infusion rate.
* Always reconstitute nebulized acetylcysteine according to manufacturer instructions, often with sterile water or saline.
* The oral antidote has a very unpleasant odor and taste, which can lead to non-compliance.
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*Please consult the current prescribing information and relevant institutional protocols for the most up-to-date and comprehensive drug information.*
