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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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Safety Of Isoniazid Preventive Treatment In Certain High Risk Groups - Statistical Data Included
From CHEST, 10/1/00 by Mohan P Philip

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, Brooklyn, NY.

PURPOSE: To study the effects of Isoniazid (INH) prophylaxis (PRx) on liver function tests (LFTs) in certain high risk groups.

METHODS: We reviewed the records of 41 patients (pts) who recieved INH PRx in directly observed therapy. The pts were divided into 2 groups (grp); grp 1 (n = 19) included those without any risk factors (RF) and grp 2 (n=22) with RF. The RF included Human Immune deficiency Virus (HIV), history of alcohol use (etoh) and Hepatitis C (HCV) positive (pos). All pts met the CDC criteria for Purified Protein Derivative (PPD) pos and received INH PRx irrespective of age. LFTs were followed at monthly intervals. Pts with pretreatment LFTs greater than or equal to ([is greater than or equal to]) 3times (t) normal (nl) values were excluded. LFT's [is greater than or equal to] 5t nl were considered significant, however the criteria to stop INH PBx was a continuous increase of LFT's beyond 5t nl or symptomatic hepatitis.

RESULTS: There was no increase of LFTs in the 19 pts in grp 1. 3 pts out of 22 in grp 2 (14%) had LFTs [greater than or equal to] 5t and all 3 were etoh, and among them 1 was also HIVpos and HCV pos. INH PRx was stopped in only one pt, because the LFTs increased to [is greater than or equal to] 10t nl. The remaining 19 pts in grp 2 (86%) did not develop abnl LFTs. There was a total of 17 pts with etoh in the study, of whom 3/17(18%) developed abnl LFTs and 14/17 (82%) did not. Of the total 41 pts studied, 33 were [is greater than or equal to] 35 years (yrs),and 2/33 (6%) developed abnl LFTs, whereas 8 pts were less than 35 yrs and 1/8 (13%) developed abnl LFTs.

CONCLUSION: Although, only a relatively small percentage of pts (13%) with RF developed abnl LFTs, all of them were etoh. HIV and HCV in the absence of etoh were not associated with increased LFTs. Age per se does not confer an increased risk . Etoh is the main risk for INH hepatotoxicity.

CLINICAL IMPLICATIONS: The overall rate of hepatotoxicity associated with INH PRx in clinically monitored pts remains low, even in those with RF .Pts with etoh are at higher risk. Clinicians should have greater confidence in the safety of INH PRx and more people should benefit from INH PRx.

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