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isoniazid

isoniazid

introduction

P/K

  • readily and completely absorbed when given orally (but reduced when taken with food)
  • peak blood levels within 1-2hrs
  • plasma half-life 1-4hrs, longer if slow inactivators, impaired hepatic or renal function
  • readily crosses BBB and placenta
  • metabolised primarily by acetylation and dehydrazination
    • rate of acetylation is genetically determined:
      • 50% of Blacks and Caucasians are slow inactivators who may have higher blood levels of the drug, and thus an increase in toxic reactions
      • most Eskimos and Orientals are rapid inactivators but this is not clinically relevant
    • newborn infants have limited acetylation capacity, which results in a prolonged elimination half-life of isoniazid

C/I

  • drug-induced hepatitis or HS reactions to INH
  • PH severe reactions to INH such as drug fever, arthritis
  • acute liver disease of unknown origin

precautions

  • severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment
    • risk increases with age and daily alcohol consumption
  • carefully monitor in patients who:
    • are receiving phenytoin or carbamazepine concurrently
    • are daily users of alcohol
    • have severe renal dysfunction
    • have chronic liver disease
    • are > 50yrs age
  • ophthalmological examinations (including ophthalmoscopy) should be done before isoniazid is started and periodically thereafter, even without occurrence of visual symptoms as there is risk of optic neuritis.
  • category A in pregnancy - should be prescribed during pregnancy only when therapeutically necessary
  • lactation - monitor infants as INH passes readily into breast milk
  • newborn infants have limited acetylation capacity and thus at risk of toxicity

interactions

adverse effects

usual dose

  • adults: 4-6mg/kg daily in divided doses (max. 300mg/day)
    • in TB meningitis, up to 10mg/kg/day can be given for 1st 1-2 wks of Rx
  • children: 5-20mg/kg daily in divided doses
isoniazid.txt · Last modified: 2014/04/10 03:57 by 127.0.0.1

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