ISONIAZID


See also "Tuberculosis"

Isoniazid is often abbreviated "INH"

I. Clinical use

  1. For prophylaxis against Tuberculosis in latent TB infection
    1. 300mg QD x 6mos; us. give pyridoxine too to reduce risk of neuropathy
    2. Use in patients over 35yo
      1. Traditionally withheld from pts > 35yo because of risk of INH-induced hepatitis
      2. In a retrospective study of 3377 pts with latent TB who were treated with INH x 6mos, incidence of hepatotoxicity (AST levels > 5x normal) were .44% for 25-34yo, .85 for 35-49yo, and 2.1 for > 50yo.  Baseline AST levels > 40U/L ass'd with RR of 5 for hepatotoxicity (Chest 128;116, 2005--JW)
      3. In a risk-analysis model, INH prophylaxis modestly increased life expectancy (& decreased health care costs) for pts, even at 50 or 70y of age; Benefits might be greater if risk of secondary transmission were taken into account (Ann. Int. Med. 127:1051, 1997--JW)

II. Adverse effects

  1. Hepatotoxicity
    1. Symptomatic hepatitis-Uncommon
      1. In one prospective cohort of 11,141 pts tx'd with INH for prophylaxis for positive PPD, incidence of hepatotoxicity (defined as AST > 5x normal or hepatitis sx resolving with w/d of INH) was 0.1%; risk was slightly higher among elderly pts (JAMA 281:1014, 1999--JW)
    2. Asymptomatic transaminase elevations are more common
    3. Alcohol consumption increases risk of hepatotoxicity
    4. When giving INH, Get baseline LFTs
    5. Consider stopping if clinical signs of liver disease ensue
  2. Peripheral Neuropathy
    1. Co-administration of pyridoxine 25-50mg/d may reduce this risk
  3. Overdose
    1. Most common presentation of acute overdose in children is sz; antidote is parenteral pyridoxine in a dose equal to mg of INH ingested; 5g if unknown