II. Indications

  1. Tuberculosis Prophylaxis
  2. Multi-drug Tuberculosis Treatment regimen

III. Background

  1. Structurally similar to Pyridoxine
  2. Interferes with formation of Mycobacteria cell walls

IV. Contraindications

  1. G6PD Deficiency
  2. Severe hepatic insufficiency (reduce INH dose)
  3. Active hepatitis
  4. End-stage liver disease

V. 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)

VI. 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%)

VII. 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

VIII. 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

IX. Drug Interactions

  1. Phenytoin (Dilantin)
    1. INH Increases blood level and toxicity
  2. Disulfiram (Antabuse)

X. 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

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Cost: Medications

isoniazid (on 5/18/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
ISONIAZID 100 MG TABLET Generic $0.09 each
ISONIAZID 300 MG TABLET Generic $0.17 each
ISONIAZID 50 MG/5 ML SOLUTION Generic $0.26 per ml

Ontology: isoniazid (C0022209)

Definition (CHV) Antibacterial agent used primarily as a tuberculostatic
Definition (CHV) Antibacterial agent used primarily as a tuberculostatic
Definition (NCI) A synthetic derivative of nicotinic acid with anti-mycobacterial properties. Although its mechanism of action is still unclear, isoniazid appears to block the synthesis of mycolic acids, major components of the mycobacterial cell wall. This agent is only active against actively growing mycobacteria because, as a pro-drug, it requires activation in susceptible mycobacterial species. Isoniazid also interferes with mycobacterial metabolism of vitamin B6. Resistance occurs due to decreased bacterial wall penetration. (NCI04)
Definition (MSH) Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.
Definition (CSP) antibacterial agent used primarily as a tuberculostatic.
Definition (PDQ) A synthetic derivative of nicotinic acid with anti-mycobacterial properties. Although its mechanism of action is still unclear, isoniazid appears to block the synthesis of mycolic acids, major components of the mycobacterial cell wall. This agent is only active against actively growing mycobacteria because, as a pro-drug, it requires activation in susceptible mycobacterial species. Isoniazid also interferes with mycobacterial metabolism of vitamin B6. Resistance occurs due to decreased bacterial wall penetration. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39484&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39484&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C600" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D007538
SnomedCT 387472004, 81335000
LNC LP15831-8, MTHU008094
English Hydrazide, Isonicotinic Acid, Isoniazid, Isonicotinic Acid Hydrazide, 4-Pyridinecarboxylic acid, hydrazide, isonicotinyl hydrazine, isonicotinic acid hydrazide, Isonicotinyl Hydrazine, isoniazid (medication), ISONIAZID, Isoniazid [Chemical/Ingredient], inh, INA - Isoniazid, INAH - Isoniazid, INH, Isonicotinic acid hydrazide, Isonicotinylhydrazide, Isoniazid (product), Isoniazid (substance), isoniazid
Swedish Isoniazid
Czech isoniazid
Finnish Isoniatsidi
Russian IZONIAZID, IZONIKOTINOVOI KISLOTY GIDRAZID, ИЗОНИАЗИД, ИЗОНИКОТИНОВОЙ КИСЛОТЫ ГИДРАЗИД
Japanese イソニアジド, ピリジン-4-カルボヒドラジド, イソニコチン酸ヒドラジド
Spanish Isoniazida, Hidrazida del Ácido Isonicotínico, Hidracida del Ácido Isonicotínico, Isoniacida, isoniacida (sustancia), isoniacida, isoniazida (producto), isoniazida (sustancia), isoniazida, isonicotinilhidrazina, ácido isonicotínco hidrazina
Polish Izoniazyd, Hydrazyd kwasu izonikotynowego
French Isoniazide
German Isoniazid, Isonicotinsäurehydrazid
Italian Isoniazide
Portuguese Hidrazida do Ácido Isonicotínico, Isoniazida