What are the recommended dosing regimens, indications, contraindications, and adverse effects of Mucomyst (N‑acetylcysteine) for mucolytic therapy, acetaminophen overdose, and contrast‑induced nephropathy prophylaxis?

Mucomyst (N-Acetylcysteine): Clinical Applications and Evidence-Based Recommendations

Contrast-Induced Nephropathy Prevention: NAC is NOT Recommended

N-acetylcysteine should not be used for prevention of contrast-induced nephropathy—major cardiology and nephrology societies explicitly classify it as ineffective (Class III, Level A evidence). 1, 2

Why NAC Fails for CIN Prevention

• The ACT trial (2,308 patients) demonstrated identical contrast-induced nephropathy rates of 12.7% in both NAC and placebo groups, with no difference in mortality or dialysis requirement (hazard ratio 0.97; 95% CI 0.56-1.69). 3, 2
• Meta-analysis restricted to high-quality trials showed no protective effect (RR 1.05; 95% CI 0.73-1.53), while apparent benefits in earlier studies were confined to trials with high risk of bias. 3, 1
• The American College of Cardiology Foundation/American Heart Association states NAC administration is "not useful" for contrast-induced AKI prevention (Level of Evidence: A). 1, 2
• The European Society of Cardiology classifies NAC as Class III (not indicated) based on Level A evidence. 1, 2

What Actually Works for CIN Prevention

Isotonic saline hydration (1.0-1.5 mL/kg/hour) for 3-12 hours before and 6-24 hours after contrast exposure is the cornerstone of renal protection (Class I recommendation). 1, 4, 2

Additional proven strategies include:

• Minimizing contrast volume to <350 mL or <4 mL/kg, maintaining contrast volume/eGFR ratio <3.4 1, 2
• Using low-osmolar or iso-osmolar contrast media (Class I recommendation) 1, 2
• Short-term high-dose statin therapy (rosuvastatin 20-40 mg, atorvastatin 80 mg, or simvastatin 80 mg) for high-risk patients (Class IIa, Level A) 1, 2
• Discontinuing nephrotoxic medications (NSAIDs, aminoglycosides) 24-48 hours before contrast exposure 1, 4

Common Pitfall to Avoid

The KDOQI commentary notes that while oral NAC is inexpensive and largely devoid of adverse effects, it should never be used instead of intravenous isotonic crystalloid in high-risk patients—hydration remains mandatory. 3 However, given the definitive negative evidence from ACT and updated guidelines, even adjunctive NAC use is no longer supported. 3, 1

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Acetaminophen Overdose: NAC is the Definitive Antidote

N-acetylcysteine is the established treatment for acetaminophen (paracetamol) poisoning and should be administered promptly when overdose is suspected. 5

Pharmacokinetics Relevant to Overdose Management

• After oral dosing (200-400 mg), peak plasma concentrations of 0.35-4 mg/L occur within 1-2 hours. 5
• Volume of distribution is 0.33-0.47 L/kg with approximately 50% protein binding at 4 hours post-dose. 5
• Terminal half-life following oral administration is 6.25 hours. 5
• Approximately 70% of total body clearance is nonrenal, with renal clearance of 0.190-0.211 L/h/kg. 5

Important Interaction

Activated charcoal may interfere with NAC absorption, with up to 96% of the drug adsorbed onto charcoal—this interaction must be considered when both agents are used in overdose management. 5

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Mucolytic Therapy for Chronic Bronchitis

N-acetylcysteine is useful as a mucolytic agent for chronic bronchitis and other pulmonary diseases complicated by viscous mucus production. 5

Standard Mucolytic Dosing

Typical oral doses range from 200-400 mg, achieving therapeutic plasma concentrations within 1-2 hours. 5

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Other Established Indications

N-acetylcysteine has proven efficacy for:

• Prevention of doxorubicin-induced cardiotoxicity 5
• Prevention of hemorrhagic cystitis from oxazaphosphorines 5

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Adverse Effects Profile

Common Side Effects

The most frequently reported adverse effects are gastrointestinal:

• Nausea 5
• Vomiting 5
• Diarrhea 5

Biochemical and Hematological Effects

Biochemical and hematological adverse effects may be observed but are generally not clinically relevant. 5

Serious Adverse Effects with IV Administration

Intravenous NAC is associated with potentially serious adverse effects and should not be routinely administered for contrast-induced nephropathy prevention. 3 This contrasts with oral NAC, which is largely devoid of adverse side effects at doses used for CIN prophylaxis (though such prophylaxis is no longer recommended). 3

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Drug Interactions

Clinically significant interactions have been documented with:

• Acetaminophen (paracetamol) 5
• Glutathione 5
• Anticancer agents 5
• Activated charcoal (up to 96% adsorption) 5

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Contraindications and Precautions

When NOT to Use NAC

Do not use NAC for prevention of postsurgical acute kidney injury in patients with impaired kidney function (KDIGO Grade 1A recommendation). 2

Do not use NAC to prevent AKI in critically ill patients with hypotension (KDIGO Grade 2D recommendation). 2

Renal Function Considerations

NAC metabolism and excretion are well-characterized, with significant nonrenal clearance (70% of total body clearance), making dose adjustments less critical than with renally-eliminated drugs. 5 However, information on whether NAC crosses the blood-brain barrier, placenta, or into breast milk is not available. 5