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Isoniazid

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Isoniazid, INH, Isonicotinic Acid Hydrazide

  • See Also
  1. Isoniazid Overdose
  2. Latent Tuberculosis
  3. Active Tuberculosis
  • Indications
  1. Latent Tuberculosis Prophylaxis
  2. Multi-drug Tuberculosis Treatment Regimen
  • Contraindications
  1. G6PD Deficiency
  2. Severe hepatic insufficiency (reduce INH dose)
  3. Active hepatitis
  4. End-stage liver disease
  • Mechanism
  1. Isoniazid was first introduced in 1952 to treat Mycobacterium tuberculosis
  2. Bactericidal agent interferes with formation of Mycobacteria cell walls (via mycolic acid synthesis blockade)
  3. Structurally similar to Pyridoxine (Vitamin B6) and Niacin (Vitamin B3)
  4. Inhibits Pyridoxine kinase, depleting active Pyridoxal Phosphate
    1. Pyridoxal Phosphate is Cofactor important in the formation of GABA from Glutamate
  • Medications
  1. Tablets: 100 and 300 mg
  2. Syrup: 50 mg/5 ml
  1. See Active Tuberculosis
  2. See Tuberculosis for specific dosing protocols and durations of treatment
  3. Tuberculosis treatment is a multi-drug regimen of which Isoniazid is a part
  4. Daily Dosing
    1. Adult: 5 mg/kg (up to 300 mg) orally or IM daily
    2. Child: 10 to 15 mg/kg (up to 300 mg) orally daily
  5. Intermittent Dosing
    1. Adult: 15 mg/kg (up to 900 mg) orally twice to three times weekly
  1. See Latent Tuberculosis
  2. Daily Dosing
    1. Adult: 300 mg orally daily
    2. Child: 10 mg/kg (up to 300 mg) orally daily
  3. Intermittent Dosing (off label, but part of ATS guidelines)
    1. Use only for directly observed dosing, in non-HIV patients for adults (and children age>12 years)
    2. Isoniazid 15 mg/kg (up to 900 mg) once weekly AND
    3. Rifapentine
  • Adverse Effects
  • Hepatic
  1. Hepatotoxicity
    1. Subclinical Hepatitis: 10%
    2. Clinical Hepatitis: 1%
    3. Risk increases with age and Alcohol intake
  2. Progressive liver damage
    1. Under age 20 years: rare
    2. Age 30 to 50 years: 1.5%
    3. Age over 50 years: 2.5%
  3. Common presenting symptoms of drug-induced hepatotoxicity
    1. Nausea or Vomiting
    2. Abdominal Pain (>50% of patients)
    3. Fever (10%)
    4. Rash (5%)
  • Adverse Effects
  • Neurologic
  1. Peripheral Neuropathy
    1. See prevention below
    2. Vitamin B6 (Pyridoxine) is important for Neurotransmitter synthesis (as well as Amino Acid synthesis)
      1. Isoniazid increases Pyridoxine urinary excretion and depletion, resulting in Peripheral Neuropathy
  2. Insomnia
  3. Restlessness
  4. Muscle Twitching
  5. Urinary Retention
  6. Seizures
  7. Psychosis
  8. Monoamine toxicity (MAO Inhibitor-like reaction)
    1. Presents with Flushing
    2. Avoid concurrent aged cheese and wine
  • Adverse Effects
  • Miscellaneous
  1. Lupus-Like Syndrome
  2. Hypersensitivity Reactions
    1. Hemolytic Anemia
    2. Stevens-Johnson Syndrome
  1. Indications for concurrent Vitamin B6 supplementation (Neuropathy risks)
    1. Pregnancy
    2. Breast Feeding infants
    3. Diabetes Mellitus
    4. Alcoholism
    5. Comorbid other Neuropathy
    6. Uremia
    7. Malnutrition
    8. HIV Infection
    9. Epilepsy
  2. Vitamin B6 (Pyridoxine)
    1. Pyridoxine 10 mg/day per 100 mg of INH
    2. Typical dose is 25-50 mg orally daily
  • Drug Interactions
  1. Phenytoin (Dilantin)
    1. INH Increases blood level and toxicity
  2. Disulfiram (Antabuse)
  1. Significant liver function abnormalities exceed 3-5 times normal with Isoniazid
    1. Stop Isoniazid if this occurs
  2. Baseline Liver Function Tests
    1. Controversial (some experts do not recommend baseline LFTs)
    2. Others recommend baseline testing and then monthly if abnormal baseline LFTs or if otherwise indicated (as below)
  3. Obtain monthly Liver Function Tests if:
    1. Abnormal baseline Liver Function Test
    2. Age >35 years
    3. History suggestive of Possible liver disorder
    4. Human Immunodeficiency Virus (HIV)
    5. Pregnancy
    6. Postpartum (within 3 months)
    7. Women who are bloack or hispanic
    8. Chronic Liver Disease
      1. Viral Hepatitis (Hepatitis B or Hepatitis C)
      2. Alcoholic Hepatitis
      3. Cirrhosis
  • Resources
  1. Isoniazid Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9499f1cf-2f46-4047-8b71-90aee7dee854
  • References
  1. (2019) Presc Lett, Resource #350309, Tuberculosis Treatment in Adults: FAQ
  2. (2012) Med Lett Drugs Ther 10(116): 29-36
  3. (2000) MMWR Recomm Rep 49(RR-6): 1-51 [PubMed]