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Isoniazid

Isoniazid is a first-line antituberculous medication used in the prevention and treatment of tuberculosis. It is often prescribed under the name INH. The chemical name is isonicotinyl hydrazine or isonicotinic acid hydrazide. more...

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It is available in tablet, syrup, and injectable forms (given via intramuscular injection), available world-wide, inexpensive to produce, and is generally well tolerated.

Mechanism of action

Isoniazid is a prodrug and must be activated by bacterial catalase. The active form inhibits the synthesis of mycolic acid in the mycobacterial cell wall.

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 quicker 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.

Isoniazid is bactericidal to rapidly-dividing mycobacteria, but is bacteriostatic if the mycobacterium is slow-growing.

Side effects

Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects, and drug interactions resulting in increased phenytoin (Dilantin) or disulfiram (Antabuse) levels.

Peripheral neuropathy and CNS effects are associated with the use of isoniazid and is due to pyridoxine (vitamin B6) depletion, but is 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.

Reference

  • Core Curriculum on Tuberculosis (2000) Division of Tuberculosis Elimination, Centers for Disease Control and Prevention

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

  • Isoniazid Overdose: Recognition and Management American Family Physician 1998 Feb 15

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The Acetylator Genes and Drug Response (Oxford Monographs on Medical Genetics) $14.74 Weekly therapy in continuation phase OK for low-risk TB: CDC likely to recommend regimen of 900 mg isoniazid, 600 mg rifapentine. (Those without HIV Infection). ... : An article from: Internal Medicine News $5.95
Gale Encyclopedia of Medicine : Tuberculosis $5.99

Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection : a 7-year evaluation from a public health tuberculosis clinic
Objectives: To determine the overall incidence of isoniazid (INN) hepatotoxicity in a public health tuberculosis clinic over a 7-year period, and to ...
Pyrazinamide and rifampin vs isoniazid for the treatment of latent tuberculosis : improved completion rates but more hepatotoxicity - clinical investigations
Context: American Thoracic Society guidelines recommend a 9-month course of therapy with isoniazid for treatment of persons with latent tuberculosis ...
Molecular Dynamics Simulation Studies of the Wild-Type, I21V, and I16T Mutants of Isoniazid-Resistant Mycobacterium tuberculosis Enoyl Reductase (InhA)
ABSTRACT The increasing prevalence of tuberculosis in many areas of the world, associated with the rise in drug-resistant Mycobacterium tuberculosis (MTB) ...
Chemical Stability of Isoniazid in an Oral Liquid Dosage Form
Abstract The chemical stability of isoniazid in an oral liquid dosage form was studied by means of a specially developed stability-indicating high-performance ...
Treatment of Isoniazid-Resistant Tuberculosis in Southeastern Texas - )
Background: Isoniazid-resistant tuberculosis (INHr-TB) can be treated successfully with several treatment regimens. However, the optimal regimen and ...
Treatment Completion and Costs of a Randomized Trial of Rifampin for 4 Months versus Isoniazid for 9 Months
There is little published information regarding treatment completion, safety, and efficacy of rifampin administered daily for 4 months-a recommended alternative ...
Safety Of Isoniazid Preventive Treatment In Certain High Risk Groups - Statistical Data Included
Mohan P Philip, MD(*); F Schmidt, MD; G Greenberg, MD; D Nazon, MD; S Nagaraju, MD and C Kunavarappu, MD. Pulmonary Medicine, Interfaith Medical Center, ...
Recall of Isoniazid Used for Antimicrobial Susceptibility Testing for Tuberculosis - Brief Article
Becton Dickinson Biosciences (Sparks, Maryland) has issued a voluntary recall of a lot of isoniazid [INH] (drug lot no. 9335260) used for antimicrobial ...

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