Drug Interactions of N-acetylcysteine (NAC)
N-acetylcysteine has relatively few significant drug interactions compared to many other medications, but certain precautions should be observed when administering NAC with other drugs to ensure safety and efficacy.
Key Drug Interactions
Concomitant medications with NAC have not been thoroughly studied for stability and safety when mixed together in nebulizer solutions 1
NAC may interact with anticoagulants, antiplatelet agents, and NSAIDs, potentially increasing bleeding risk due to its effects on glutathione pathways and free radical scavenging properties 2
When administering NAC for acetaminophen overdose, oral therapy is contraindicated if:
- Patient is in coma
- Patient is experiencing vomiting
- Activated charcoal has been previously administered orally 3
Pharmacokinetic Considerations
NAC forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides in vivo, which may affect metabolism of other drugs through glutathione-dependent pathways 3, 4
NAC increases glutathione synthesis (from 0.54 to 2.69 μmol/g per hour in experimental models), which can affect detoxification of other medications metabolized through glutathione-dependent pathways 4
NAC serves as a sulfhydryl group donor, which may influence the metabolism of drugs that undergo conjugation with sulfhydryl groups 5
Adverse Reactions with Potential Drug Interaction Implications
Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into NAC infusion in up to 10% of patients 3
Cutaneous anaphylactoid reactions (flushing, rash, pruritus) appear to be more common in patients with lower serum acetaminophen concentrations when receiving NAC for acetaminophen overdose 6
Gastrointestinal side effects including nausea, vomiting, and diarrhea may occur with oral NAC administration, which could affect absorption of concomitantly administered medications 3
Clinical Applications and Interaction Considerations
NAC is primarily used in acetaminophen overdose, where it serves as the mainstay of treatment when administered as an 18-dose oral course or intravenous regimen 5
NAC has chelating properties that may enhance elimination of heavy metals, which could potentially interact with metal-containing medications or supplements 5
NAC has antioxidant properties that may affect oxidative drug metabolism pathways, potentially altering the efficacy or toxicity profiles of drugs metabolized through these pathways 7
When switching between anticoagulant regimens and NAC therapy, careful monitoring is recommended due to potential interactions affecting bleeding risk 2
Precautions and Monitoring
Drug stability and safety of NAC when mixed with other drugs in a nebulizer have not been established, requiring caution when co-administering aerosolized medications 1
Monitor for increased bleeding risk when NAC is administered with anticoagulants, antiplatelet agents, or NSAIDs 2
Consider dose adjustments when administering NAC with drugs that may compete for similar metabolic pathways or when treating patients with hepatic or renal impairment 7