NAC Does Not Increase INR
N-acetylcysteine (NAC) is not documented to increase INR in patients taking warfarin based on available guideline evidence. The comprehensive 2022 American Heart Association guideline on drug interactions affecting oral anticoagulant use does not list NAC among the numerous medications and supplements known to interact with warfarin 1.
Evidence Analysis
The most recent and authoritative guideline systematically addresses warfarin interactions across multiple drug classes, including 1:
- Antivirals (ritonavir, oseltamivir, efavirenz)
- Cardiovascular medications (statins, fibrates, fish oil)
- Psychotropics (SSRIs, carbamazepine, phenytoin)
- Chemotherapy agents (fluorouracil, capecitabine)
- Herbal supplements (St. John's wort, ginseng, ginkgo, ginger, green tea, cranberry) 2
- Miscellaneous agents (alcohol, omeprazole, danazol) 2
NAC is conspicuously absent from this comprehensive list, suggesting no clinically significant interaction has been established.
Clinical Context
While the absence of documented interaction does not equal proven safety 2, the following considerations apply:
- Known INR-increasing medications are well-characterized and include acetaminophen (≥2 g/day for consecutive days) 3, 4, 5, certain statins 1, and SSRIs 1
- Multiple mechanisms can cause warfarin interactions: CYP2C9 inhibition/induction, protein binding displacement, and alteration of vitamin K-producing gut flora 2
- NAC lacks documentation through any of these established mechanisms
Practical Management Approach
If NAC must be initiated in a warfarin-treated patient:
- Monitor INR within 3-7 days of starting NAC and again at 2-3 weeks, as recommended for any new medication in warfarin-treated patients 2
- Maintain target INR 2.0-3.0 with time in therapeutic range ≥65% 3
- Educate patients that any new medication or supplement should be discussed before initiation 2
Important Caveats
- Supplement data limitations: Most interaction data comes from case reports, making true incidence difficult to establish 2
- INR variability: Even with careful monitoring, 87% of warfarin patients experience at least one INR <1.5, and 49% experience at least one INR >4.0 during therapy 6
- Brief warning periods: Serial INRs are poor predictors of hemorrhagic events, with only a brief period (mean 11.6 days) of slightly elevated INR before bleeding occurs 7