Isoniazid

Aka: Isoniazid, INH

1. Indications
   1. Tuberculosis Prophylaxis
   2. Multi-drug Tuberculosis Treatment regimen
2. Background
   1. Structurally similar to Pyridoxine
   2. Interferes with formation of Mycobacteria cell walls
3. Contraindications
   1. G6PD Deficiency
   2. Severe hepatic insufficiency (reduce INH dose)
   3. Active hepatitis
   4. End-stage liver disease
4. Dosing
   1. See Tuberculosis for specific dosing protocols and durations of treatment
   2. Daily dosing
      1. Adult: 300 mg PO or IM
      2. Child: 5 mg/kg (up to 300 mg daily)
   3. Intermittent dosing
      1. Adult: 900 mg orally twice weekly (15 mg/kg twice weekly)
5. 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%)
6. Adverse Effects: Neurologic
   1. Peripheral Neuropathy
      1. See prevention below
   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
7. Prevention: Peripheral Neuropathy
   1. Indications for concurrent Vitamin B6 supplementation (Neuropathy risks)
      1. Pregnancy
      2. Diabetes Mellitus
      3. Alcoholism
      4. Comorbid other Neuropathy
      5. Uremia
      6. Malnutrition
      7. HIV Infection
      8. Epilepsy
   2. Vitamin B6 (Pyridoxine)
      1. Pyridoxine 10 mg/day per 100 mg of INH
      2. Typical dose is 25-50 mg orally daily
8. Drug Interactions
   1. Phenytoin (Dilantin)
      1. INH Increases blood level and toxicity
   2. Disulfiram (Antabuse)
9. Monitoring: Liver Function Tests
   1. Significant liver function abnormalities exceed 3-5 times normal with Isoniazid
   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. History suggestive of Possible liver disorder
      3. Human Immunodeficiency Virus (HIV)
      4. Pregnancy
      5. Postpartum (within 3 months)
      6. Chronic Liver Disease
         1. Viral Hepatitis (Hepatitis B or Hepatitis C)
         2. Alcoholic Hepatitis
         3. Cirrhosis
10. References
    1. (2000) MMWR Recomm Rep 49(RR-6): 1-51 [PubMed]