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Systematic (IUPAC) name
Clinical data
  • C
Routes of
oral, intramuscular, intravenous
Legal status
Legal status
  • prescription only (US)
Pharmacokinetic data
Protein binding Very low (0-10%)
Metabolism liver; CYP450: 2C19, 3A4 inhibitor
Biological half-life 0.5-1.6h (fast acetylators), 2-5h (slow acetylators)
Excretion urine (primarily), feces
CAS Number 54-85-3
ATC code J04AC01 (WHO)
PubChem CID 3767
DrugBank APRD01055
ChemSpider 3635
Chemical data
Formula C6H7N3O
Molar mass 137.139 g/mol[[Script error: No such module "String".]]
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Isoniazid (Laniazid, Nydrazid), also known as isonicotinylhydrazine (INH), is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis. Isoniazid is never used on its own to treat active tuberculosis because resistance quickly develops. Isoniazid also has an antidepressant effect, and it was one of the first antidepressants discovered.

The compound was first synthesised in the early 20th century,[1] but its activity against tuberculosis was first reported in the early 1950s and three pharmaceutical companies attempted unsuccessfully to simultaneously patent the drug[2] (most prominently, Roche, who launched their version, Rimifon, in 1952). With the introduction of isoniazid, a cure for tuberculosis was first considered reasonable.

Isoniazid is available in tablet, syrup, and injectable forms (given intramuscularly or intravenously). Isoniazid is available worldwide, is inexpensive and is generally well tolerated. It is manufactured from isonicotinic acid, which is produced from 4-methylpyridine.[3]


Isoniazid may be prepared by the base hydrolysis of 4-cyanopyridine to give the amide, followed by displacement of ammonia by hydrazine:[4]


Mechanism of action

Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme called KatG.[5] KatG couples the isonicotinic acyl with NADH to form isonicotinic acyl-NADH complex. This complex binds tightly to the enoyl-acyl carrier protein reductase known as InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase. This process inhibits the synthesis of mycolic acid, required for the mycobacterial cell wall. A range of radicals are produced by KatG activation of Isoniazid, including nitric oxide[6] which has also been shown to be important in the action of another antimycobacterial prodrug PA-824.[7]

Isoniazid is bactericidal to rapidly-dividing mycobacteria but is bacteriostatic if the mycobacterium is slow-growing.[citation needed] Isoniazid inhibits the P450 system.Template:Pharmacology,Harvey 4th edition


Isoniazid reaches therapeutic concentrations in serum, cerebrospinal fluid (CSF), and within caseous granulomas. Isoniazid is metabolized in the liver via acetylation. There are two forms of the enzyme responsible for acetylation, so that some patients metabolize the drug more quickly than others. Hence, the half-life is bimodal with peaks at 1 hour and 3 hours in the US population. The metabolites are excreted in the urine. Doses do not usually have to be adjusted in case of renal failure.


The standard dose of isoniazid in adults is 5 mg/kg/day (max 300 mg daily). When prescribed intermittently (twice or thrice weekly) the dose is 15 mg/kg (max 900 mg daily). Patients with slow clearance of the drug (via acetylation as described above) may require reduced dosages to avoid toxicity. The recommended dose for children is 8 to 12 mg/kg/day.[8]

Side effects

Adverse reactions include rash, abnormal liver function tests, hepatitis, sideroblastic anemia, high anion gap metabolic acidosis, peripheral neuropathy, mild central nervous system (CNS) effects, drug interactions resulting in increased phenytoin (Dilantin) or disulfiram (Antabuse) levels and intractable seizures (status epilepticus).

Peripheral neuropathy and CNS effects are associated with the use of isoniazid and are due to pyridoxine (vitamin B6) depletion, but are uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10–50 mg/day) with isoniazid.

Hepatotoxicity of INH is by nitrogen group in its chemical structure,as it is metabolized in liver and gets converted in to ammonium molecule which causes hepatitis.

Hepatotoxicity can be avoided with close clinical monitoring of the patient, specifically nausea, vomiting, abdominal pain and appetite. Isoniazid is metabolized by the liver mainly by acetylation and dehydrazination. The N-acetylhydrazine metabolite is believed to be responsible for the hepatotoxic effects seen in patients treated with isoniazid. The rate of acetylation is genetically determined. Approximately 50% of blacks and Caucasians are slow inactivators; the majority of Inuit and Asians are rapid inactivators. The half-life in fast acetylators is 1 to 2 hours while in slow acetylators it is 2 to 5 hours. Elimination is largely independent of renal function, however the half-life may be prolonged in liver disease. The rate of acetylation has not been shown to significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood concentrations with chronic administration of the drug, with an increased risk of toxicity. Isoniazid and its metabolites are excreted in the urine with 75 to 95% of the dose excreted in 24 hours. Small amounts are also excreted in saliva, sputum and feces. Isoniazid is removed by hemodialysis and peritoneal dialysis.[9]

Headache, poor concentration, weight-gain, poor memory and depression have all been associated with isoniazid use. All patients and health-care workers should be aware of these serious adverse effects, especially if suicidal thinking or behavior are suspected.[10][11][12]

INH is known to reduce cytochrome P450 and in theory promote the efficacy of Contraceptives. Therapy is often combined with Rifampin. Rifampin increases the P450 enzyme and can reduce the efficacy of contraceptives. Alternative means of birth control should be used when taking these medications.

As p450 is required for porphyrin synthesis its deficiency leads to poor heam formation in early RBCs leads to sideroblastic anemia.

Synonyms and abbreviations

  • Isonicotinyl hydrazine
  • Isonicotinic acid hydrazide
  • INH
  • H (for "hydrazide", and also the WHO standard abbreviation)

See also


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External links

See Chapter 6, Treatment of LTBI Regimens - Isoniazid::
See Chapter 7 - Treatment of TB Disease Monitoring - Adverse Reactions to First-Line TB Drugs - Isoniazid::
See Table 5 First-Line Anti-TB Medications

da:Isoniazid de:Isoniazid es:Isoniacida fa:ایزونیازید fr:Isoniazide it:Isoniazide nl:Isoniazide ja:イソニアジド nn:Isoniazid pl:Izoniazyd pt:Isoniazida ru:Изониазид sv:Isoniazid

  1. Meyer H, Mally J (1912). "On hydrazine derivatives and pyridine carbonic acids". Monatshefte Chemie verwandte Teile anderer Wissenschaften (in German). 23: 393–414. 
  2. Hans L Riede (2009). "Fourth-generation fluoroquinolones in tuberculosis". Lancet. 373 (9670): 1148–1149. doi:10.1016/S0140-6736(09)60559-6. 
  3. Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura (2007). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. New York: John Wiley & Sons. [page needed]
  4. T. P. Sycheva, T. N. Pavlova and M. N. Shchukina (1972). "Synthesis of isoniazid from 4-cyanopyridine". Pharmaceutical Chemistry Journal. 6 (11): 696–698. doi:10.1007/BF00771896. 
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