Isoniazid and NAT2
Isoniazid is inactivated by NAT2 acetylation. Slow acetylators accumulate more of the hepatotoxic intermediate and have a several-fold higher rate of drug-induced liver injury.
Why does NAT2 matter for Isoniazid?
Isoniazid is inactivated by NAT2 acetylation. Slow acetylators accumulate more of the hepatotoxic intermediate and have a several-fold higher rate of drug-induced liver injury. NAT2 inactivates drugs by acetylation. Its common haplotypes split people into rapid, intermediate and slow acetylators, and the split is strongly population-dependent: about half of Europeans and South Asians are slow acetylators, against roughly one in ten East Asians. Slow acetylators clear isoniazid, hydralazine, sulfasalazine, dapsone and procainamide more slowly and are more prone to their toxicities, from isoniazid liver injury to hydralazine-induced lupus.
What does CPIC recommend for each NAT2 phenotype on Isoniazid?
The guidance below is the CPIC recommendation for prescribers, reproduced for reference. It is written for a clinician who knows the whole picture — never start, stop or change a medicine on the basis of this page.
| Phenotype | CPIC-based guidance |
|---|---|
| Rapid Acetylator | Standard dose. Monitor for treatment efficacy as rapid acetylators may have lower drug exposure. Consider therapeutic drug monitoring if poor response. |
| Intermediate Acetylator | Standard dose. Standard monitoring for hepatotoxicity (ALT/AST at baseline and periodically). |
| Slow Acetylator | Consider reduced dose or enhanced hepatotoxicity monitoring. Slow acetylators have 4-6× higher risk of isoniazid-induced liver injury. Monitor ALT/AST closely, especially in first 2 months. |
Which NAT2 alleles decide the phenotype?
The phenotype is read from the two NAT2 star alleles a person carries. The full allele table, with the defining variants and their population frequencies, is on the NAT2 gene page.
NAT2 haplotypes are inferred from a panel of seven coding SNPs; consumer chips usually carry the four that define the common slow alleles (rs1801279, rs1801280, rs1799930, rs1799931). Phase — which variants sit on the same chromosome — is not observed directly, so the diplotype is a statistical inference.
Other drugs affected by NAT2
- Hydralazine — Antihypertensive (vasodilator)
- Sulfasalazine — Anti-inflammatory (DMARD)
- Procainamide — Antiarrhythmic
- Dapsone — Anti-infective / Anti-inflammatory
- Caffeine — Stimulant (methylxanthine)
Upload your raw DNA file and see your metaboliser status → · Ask G2: “Does my NAT2 genotype affect Isoniazid?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.