BSN Tracker

isoniazid

Brand: INH, Nydrazid

⚠ BBW Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: antimycobacterial
Organ Systems: infectious-disease

Mechanism of Action

Prodrug activated by mycobacterial catalase-peroxidase (KatG); active intermediate inhibits InhA and KasA, enzymes required for mycolic acid synthesis (a unique component of mycobacterial cell walls); bactericidal against actively dividing mycobacteria.

InhA (enoyl-ACP reductase)KasA (beta-ketoacyl-ACP synthase)

Indications

  • tuberculosis treatment (first-line; always combined with other agents)
  • latent TB infection (LTBI) — 9 months or 3 months with rifapentine/rifampin short-course

Contraindications

  • severe isoniazid-induced liver disease
  • severe hypersensitivity to isoniazid

Adverse Effects

Common

  • peripheral neuropathy (dose-dependent; prevented by pyridoxine B6 supplementation)
  • hepatotoxicity (transient LFT elevation in 10–20%; clinical hepatitis 0.1–2%)
  • rash

Serious

  • hepatotoxicity (drug-induced hepatitis — fatal cases reported; risk increases with age, alcohol use, pre-existing liver disease)
  • peripheral neuropathy (irreversible without pyridoxine)
  • lupus-like syndrome
  • psychosis

Pharmacokinetics (ADME)

Absorption Nearly complete oral absorption; reduced by food and antacids
Distribution Protein binding 10–15%; widely distributed including CSF, caseous tissue; Vd ~0.6 L/kg
Metabolism NAT2 (N-acetyltransferase 2) acetylation — pharmacogenomic: slow acetylators have higher drug levels and more neuropathy; fast acetylators may have lower efficacy and more acetylhydrazine hepatotoxicity
Excretion Renal; metabolites excreted in urine
Half-life 1–4 hours (fast acetylators); 2–5 hours (slow acetylators)
Onset Antituberculous effect: weeks
Peak 1–2 hours
Duration 24 hours
Protein Binding 10–15%
Vd ~0.6 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
phenytoin isoniazid inhibits CYP2C9, increasing phenytoin levels and toxicity major
pyridoxine (B6) isoniazid depletes pyridoxine; supplementation prevents peripheral neuropathy moderate
rifampin combined with isoniazid in TB therapy; rifampin induces isoniazid metabolism via CYP but they are used together for synergy moderate

Nursing Considerations

  1. Administer pyridoxine (vitamin B6) 25–50 mg/day concurrently to prevent peripheral neuropathy — especially important in patients with diabetes, malnutrition, HIV, pregnancy, and renal failure
  2. Monitor LFTs at baseline and monthly in patients with risk factors (age >35, daily alcohol use, chronic liver disease, concurrent hepatotoxic drugs); hold INH if ALT >5x ULN (asymptomatic) or >3x ULN with symptoms
  3. Administer on empty stomach (1 hour before or 2 hours after meals) for maximum absorption; antacids also reduce absorption
  4. Instruct patients not to consume alcohol during TB treatment; report nausea, vomiting, abdominal pain, jaundice, or tingling/numbness in extremities immediately

Clinical Pearls

  • Isoniazid peripheral neuropathy is caused by competitive inhibition of pyridoxine phosphokinase — it is entirely preventable with pyridoxine 25–50 mg/day; neuropathy that does develop may be irreversible
  • NAT2 acetylator status (pharmacogenomic variation) significantly affects isoniazid pharmacokinetics and toxicity profile — slow acetylators have 3–5x higher drug levels with greater neuropathy risk; fast acetylators may have lower efficacy

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Antibiotic Latent TB Infection (LTBI) — 9 Months Or 3 Months With Rifapentine/rifampin Short-course Tuberculosis Treatment (first-line; Always Combined With Other Agents)
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