Isoniazid: An overview
- Richard H Drew, PharmD, MS, FCCP
Richard H Drew, PharmD, MS, FCCP
- Professor, Campbell University College of Pharmacy and Health Sciences
- Associate Professor and Clinical Pharmacist, Infectious Diseases
- Duke University Medical Center
Isoniazid is used for treatment of tuberculosis (as part of combination therapy) or for latent tuberculosis infection (as monotherapy or part of combination therapy). Less frequently, isoniazid may be used as part of a combination regimen for nontuberculous mycobacterial infections.
Basic issues related to clinical use of isoniazid will be reviewed here. The clinical settings in which isoniazid may be used are discussed separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults" and "Treatment of latent tuberculosis infection in HIV-uninfected adults" and "Treatment of pulmonary tuberculosis in HIV-infected adults" and "Treatment of latent tuberculosis infection in HIV-infected adults" and "Treatment of Mycobacterium avium complex lung infection".)
Mechanism of action — The antimicrobial activity of isoniazid (INH) is selective for mycobacteria, likely due to its ability to inhibit mycolic acid synthesis, which interferes with cell wall synthesis, thereby producing a bactericidal effect . INH also disrupts DNA, lipid, carbohydrate, and nicotinamide adenine dinucleotide (NAD) synthesis and/or metabolism.
Spectrum of activity — INH is active against intracellular and extracellular Mycobacterium tuberculosis. The organism is considered most susceptible to INH during its logarithmic phase of growth . The minimum inhibitory concentration (MIC) of M. tuberculosis for INH ranges from 0.01 to 0.25 mcg/mL. The MICs and minimum bactericidal concentrations (MBCs) for the organism are equivalent for most isolates .
Of the atypical mycobacteria spp, M. kansasii and M. xenopi are considered the most susceptible, while M. avium complex is generally resistant to INH.
- Berning SE, Peloquin CA. Antimycobacterial agents: Isoniazid. In: Antimicrobial Therapy and Vaccines, Yu V, Merigan T, Barriere S (Eds), Williams and Wilkins, Baltimore 1998.
- Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Ann Intern Med 1997; 127:289.
- Ellard GA, Gammon PT. Pharmacokinetics of isoniazid metabolism in man. J Pharmacokinet Biopharm 1976; 4:83.
- Grange JM, Winstanley PA, Davies PD. Clinically significant drug interactions with antituberculosis agents. Drug Saf 1994; 11:242.
- Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000; 161:S221.
- Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998; 47:1.
- Zhang Y, Vilcheze C, Jacobs WR. Mechanisms of drug resistance in Mycobacterium tuberculosis. In: Tuberculosis and the Tubercle Bacillus, Cole ST, Eisenach KD, McMurray DN, Jacobs WR (Eds), ASM Press, Washington, DC 2005.
- Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2013. US Department of Health and Human Services, Atlanta, GA 2013. http://www.cdc.gov/tb/statistics/reports/2013/pdf/report2013.pdf (Accessed on May 04, 2015).
- Centers for Disease Control and Prevention (CDC). Impact of a shortage of first-line antituberculosis medication on tuberculosis control - United States, 2012-2013. MMWR Morb Mortal Wkly Rep 2013; 62:398.
- Centers for Disease Control and Prevention. Emergency Preparedness and Response. http://emergency.cdc.gov/HAN/han00340.asp (Accessed on July 16, 2013).
- Centers for Disease Control and Prevention. Tuberculosis. http://www.cdc.gov/tb/ (Accessed on July 16, 2013).
- Mechanism of action
- Spectrum of activity
- Drug interactions
- CLINICAL USE
- Dosing and administration
- Clinical monitoring
- Special populations
- - Patients with hepatic dysfunction
- - Pregnant or breastfeeding women
- Adverse reactions
- - Neurologic reactions
- - Hepatotoxicity
- - Other reactions
- Drug resistance
- Drug shortages
- INFORMATION FOR PATIENTS