Meta Information
ID:nac
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/nitrates
Target name:
Nitrate Medications
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NAC potentiates the vasodilatory effects of nitrates (e.g., nitroglycerin), which can lead to a dangerous drop in blood pressure (hypotension) and severe headaches.
Actionable advice:
NAC should not be taken with nitrate medications unless under strict medical supervision.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
BACKGROUND: N-acetylcysteine (NAC) has been shown to potentiate the effects of nitroglycerin (NTG) and to have antioxidant activity.
Label source:
PubMed: N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving acute myocardial infarction. Safety and biochemical effects. (PMID 7586252)
Action type:
avoid
Target id:
/condition/bleeding-disorders
Target name:
Bleeding Disorders
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its ability to inhibit platelet aggregation, NAC can increase the risk of bleeding in individuals with pre-existing bleeding disorders like hemophilia.
Actionable advice:
NAC should be avoided with a known bleeding disorder.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.
Label source:
PubMed: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (2006)
Source url:
Exact phrase from label:
Inhibition of platelet ROS by NAC reduced platelet aggregation, activation, and apoptosis, and prolonged bleeding time.
Label source:
PubMed: Thrombosis research (2023)
Source url:
Exact phrase from label:
Both preclinical models demonstrate that NAC prevents thrombus formation in a dose-dependent manner without significantly affecting bleeding time.
Label source:
PubMed: Arteriosclerosis, thrombosis, and vascular biology (2024)
Action type:
avoid
Target id:
/procedure/surgery
Target name:
Scheduled Surgery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
NAC's antiplatelet effects increase the risk of excessive bleeding during and after surgical procedures.
Actionable advice:
NAC should be discontinued at least 2 weeks before any scheduled surgery.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
N-acetylcysteine did not appear to increase the risk of surgical reexploration for bleeding (OR, 1.16; 95% CI, 0.57 to 2.38) or amount of allogeneic blood transfusion required (WMD in units, 0.31; 95% CI, -0.21 to 0.84).
Label source:
PubMed: American journal of kidney diseases : the official journal of the National Kidney Foundation (2009)
Source url:
Exact phrase from label:
Our results revealed that NAC, compared with the placebo, did not provide an additional clinical benefit as an effective antiplatelet agent after PCI.
Label source:
PubMed: American journal of therapeutics (2016)
Source url:
Exact phrase from label:
NAC treatment partly or completely reversed the effects of diabetes. CONCLUSION: Collectively, these results show that the diabetic blood and brain become progressively more susceptible to platelet activation and thrombosis. NAC, given after the establishment of diabetes, may offer protection against the risk for stroke by altering both systemic and vascular prothrombotic responses via enhancing platelet GSH, and GSH-dependent MG elimination, as well as correcting levels of antioxidants such as SOD1 and GPx-1.
Label source:
PubMed: Redox biology (2018)
Action type:
avoid
Target id:
/intervention/activated-charcoal
Target name:
Activated Charcoal
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Activated charcoal is a potent adsorbent that will bind to NAC in the gastrointestinal tract, preventing its absorption into the bloodstream.
Actionable advice:
NAC and activated charcoal should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A reduction in peak NAC level of 29% (P less than .02) and a reduction of total area under the curve (AUC) of 39% (P less than .001) was noted.
Label source:
PubMed: The American journal of emergency medicine (1987)
Source url:
Exact phrase from label:
N-acetylcysteine was adsorbed by activated charcoal, lending in vitro support to previous clinical of activated charcoal for NAC in biologic fluid was significantly greater than in nonbiologic fluid and has important clinical implications.
Label source:
PubMed: Veterinary and human toxicology (1980)
Source url:
Exact phrase from label:
Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal.
Label source:
PubMed: Clinical pharmacokinetics (1991)
Action type:
separate
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NAC has antiplatelet properties that can additively increase the risk of bleeding when combined with medications like warfarin, clopidogrel, or aspirin.
Actionable advice:
This is best used with caution and under medical supervision when taking any blood-thinning medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Major bleeding episodes were not more frequent among patients receiving aspirin plus warfarin than among those receiving warfarin alone, but the incidence of minor bleeding episodes was higher in the combined therapy group.
Label source:
Action type:
informational_none
Target id:
/class/chemotherapy-radiation
Target name:
Cytotoxic Cancer Therapies (Chemotherapy & Radiation)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a potent antioxidant, NAC could theoretically protect cancerous cells from the oxidative damage intended by chemotherapy or radiation, potentially reducing treatment efficacy.
Actionable advice:
NAC is best avoided during active cancer treatment unless specifically directed by an oncologist.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
This trial compared the addition of tamoxifen or placebo to treatment with lumpectomy and radiation therapy for women with DCIS.
Label source:
Action type:
avoid
Target id:
/condition/asthma-copd
Target name:
Asthma and COPD
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
While more common with inhaled NAC, oral NAC can rarely trigger bronchospasm (airway narrowing) in susceptible individuals with asthma.
Actionable advice:
This is best used with caution, starting with a low dose in those with asthma, and discontinued if wheezing occurs.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Exact phrase from label:
NAC infusion should be used cautiously in patients with a history of bronchospasm or asthma.
Label source:
Clinical guidance: StatPearls — N-Acetylcysteine (NBK537183)
Action type:
avoid
Target id:
/condition/peptic-ulcer-disease
Target name:
Peptic Ulcer Disease (PUD)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NAC can break down the protective gastric mucus layer, which may irritate the stomach lining and potentially worsen active peptic ulcers.
Actionable advice:
NAC is best avoided with an active peptic ulcer, or taken with food with a history of ulcers.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Pretreatment with NAC improved the inflammatory, apoptotic, and redox status in a dose-dependent manner
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/28092180/
Action type:
avoid
Target id:
/condition/histamine-intolerance
Target name:
Histamine Intolerance
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NAC can inhibit diamine oxidase (DAO), the primary enzyme for breaking down histamine, potentially worsening symptoms like flushing or headaches in those with histamine intolerance.
Actionable advice:
This is best avoided or used with extreme caution by those with known histamine intolerance.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Expectorants, mucolytics | ambroxol, N-acetylcysteine
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC8308327/
Action type:
avoid
Target id:
/intervention/glycine
Target name:
Glycine
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Glycine is a required precursor alongside cysteine (from NAC) for the synthesis of glutathione; co-administration ensures both building blocks are available.
Actionable advice:
Glycine is best taken at the same time as NAC to support optimal glutathione production (often as a combined GlyNAC supplement).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR).
Label source:
PubMed: Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (PMID 35975308)
Action type:
informational_none
Target id:
/intervention/selenium
Target name:
Selenium
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Selenium is an essential cofactor for the enzyme glutathione peroxidase, which utilizes the glutathione produced from NAC to neutralize oxidative damage.
Actionable advice:
Adequate selenium intake from diet or supplements is a good idea when taking NAC for long-term antioxidant support.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In particular, zinc and selenium function as structural and catalytic cofactors for antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, while vitamins A and D regulate cellular differentiation and calcium-phosphorus metabolism through transcriptional control mechanisms.
Label source:
PubMed: Mineral-Vitamin Complexes in Sheep Nutrition: Patent Analysis and Functional Evaluation for Pregnant Ewes and Lambs. (PMID 41900039)
Action type:
informational_none
Target id:
/intervention/exercise
Target name:
Exercise
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High-dose antioxidant supplementation around the time of exercise may blunt the natural oxidative stress signals that are necessary for training adaptations like mitochondrial biogenesis.
Actionable advice:
NAC is generally best separated from a workout by at least 2 hours to maximize training benefits.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Antioxidant supplementation may hamper exercise-induced cellular adaptations.
Label source:
PubMed: Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. (PMID 23719546)
Action type:
separate
Target id:
/class/ace-inhibitors
Target name:
ACE Inhibitors
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
NAC may enhance the blood pressure-lowering effect of ACE inhibitors, potentially by improving endothelial function and nitric oxide availability.
Actionable advice:
It is a good idea to check blood pressure when starting NAC while on an ACE inhibitor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
8.6 Race
ACE inhibitors, including Zestril, have an effect on blood pressure that is less in black patients than in non blacks.
Label source:
Action type:
monitor
Target id:
/intervention/molybdenum
Target name:
Molybdenum
Severity:
minor
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Molybdenum is a cofactor for sulfite oxidase, an enzyme that metabolizes sulfites, which can be produced during NAC metabolism.
Actionable advice:
Adequate molybdenum intake is generally best maintained, as deficiency could lead to sulfite sensitivity when supplementing with NAC.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Molybdenum cofactor deficiencies (MoCD) are a group of inborn errors of metabolism that result in impaired synthesis of molybdenum cofactor, crucial for the function of three oxidases (sulfite oxidase, xanthine oxidase and aldehyde oxidase).
Label source:
PubMed: Early postnatal hepatocyte transplantation in a child with molybdenum cofactor deficiency type B. (PMID 40121797)
Action type:
informational_none
Target id:
/intervention/carbamazepine
Target name:
Carbamazepine
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There is weak evidence from case reports suggesting that high-dose NAC might increase the clearance of carbamazepine, potentially lowering its therapeutic levels.
Actionable advice:
If taking carbamazepine, discuss NAC use with your doctor as monitoring of drug levels may be warranted.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CYP3A4 inducers can increase the rate of Tegretol metabolism. Drugs that have been shown, or that would be
expected, to decrease plasma carbamazepine levels include cisplatin, doxorubicin HCl, felbamate, fosphenytoin,
rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline.
Label source:
FDA label: Carbamazepine [class-derived from: Carbamazepine]
Action type:
monitor