Isoniazid Hepatotoxicity Differential Diagnoses

  • Author: Richard A Weisiger, MD, PhD; Chief Editor: Julian Katz, MD   more...
 
Updated: May 23, 2012
 
 

Diagnostic Considerations

Diagnosis of isoniazid (isonicotinic acid hydrazide [INH]) hepatotoxicity requires exclusion of other causes of hepatitis.

Potential toxicity from other drugs must be considered. Exclude exogenous hepatotoxins, such as chlorinated hydrocarbons, poisonous mushrooms, and halothane (where it is still used), through a careful review of the patient’s history. Other drugs commonly used with INH that also may produce hepatotoxicity include protease inhibitors (for treating HIV) and pyrazinamide.

Other causes of seizures should also be considered.

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Richard A Weisiger, MD, PhD  Director, GI and Liver Faculty Practice, Professor, Department of Internal Medicine, University of California, San Francisco, School of Medicine

Richard A Weisiger, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases and American Society for Clinical Investigation

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD  Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Additional Contributors

John G Benitez, MD, MPH, FACMT, FAACT, FACPM, FAAEM, Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH, FACMT, FAACT, FACPM, FAAEM, is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Terence David Lewis, MBBS, FRACP, FRCPC, FACP Program Director, Internal Medicine Residency, & Assistant Chairman, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, Loma Linda University Medical Center

Terence David Lewis, MBBS, FRACP, FRCPC, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, and Sigma Xi

Disclosure: Nothing to disclose.

C Crawford Mechem, MD, MS, FACEP Associate Professor, Department of Emergency Medicine, University of Pennsylvania School of Medicine; Emergency Medical Services Medical Director, Philadelphia Fire Department

C Crawford Mechem, MD, MS, FACEP is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Binita R Shah, MD, FAAP Professor of Clinical Pediatrics and Emergency Medicine, SUNY Health Sciences Center at Brooklyn; Director of Pediatric Emergency Medicine, Departments of Emergency Medicine and Pediatrics, Kings County Hospital Center

Binita R Shah, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

David Tran, MD Attending Physician, Department of Emergency Medicine, North Shore-LIJ Plainview Hospital

David Tran, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

William T Zempsky, MD Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center

William T Zempsky, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

References

  1. Agrawal RL, Dwivedi NC, Agrawal M, Jain S, Agrawal A. Accidental isoniazid poisoning--a report. Indian J Tuberc. Apr 2008;55(2):94-6. [Medline].

  2. Tostmann A, Boeree MJ, Peters WH, Roelofs HM, Aarnoutse RE, van der Ven AJ, et al. Isoniazid and its toxic metabolite hydrazine induce in vitro pyrazinamide toxicity. Int J Antimicrob Agents. Jun 2008;31(6):577-80. [Medline].

  3. Roy PD, Majumder M, Roy B. Pharmacogenomics of anti-TB drugs-related hepatotoxicity. Pharmacogenomics. Mar 2008;9(3):311-21. [Medline].

  4. Taylor Z, Nolan CM, Blumberg HM. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. Nov 4 2005;54:1-81. [Medline].

  5. Schwab CE, Tuschl H. In vitro studies on the toxicity of isoniazid in different cell lines. Hum Exp Toxicol. Nov 2003;22(11):607-15. [Medline].

  6. Ben Mahmoud L, Ghozzi H, Kamoun A, Hakim A, Hachicha H, Hammami S, et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatotoxicity in Tunisian patients with tuberculosis. Pathol Biol (Paris). Aug 17 2011;[Medline].

  7. Vuilleumier N, Rossier MF, Chiappe A, Degoumois F, Dayer P, Mermillod B, et al. CYP2E1 genotype and isoniazid-induced hepatotoxicity in patients treated for latent tuberculosis. Eur J Clin Pharmacol. Jun 2006;62(6):423-9. [Medline].

  8. Yamada S, Tang M, Richardson K, et al. Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population. Pharmacogenomics. Sep 2009;10(9):1433-45. [Medline].

  9. Yue J, Peng R. Does CYP2E1 play a major role in the aggravation of isoniazid toxicity by rifampicin in human hepatocytes?. Br J Pharmacol. Jun 2009;157(3):331-3. [Medline].

  10. Ozick LA, Jacob L, Comer GM, Lee TP, Ben-Zvi J, Donelson SS, et al. Hepatotoxicity from isoniazid and rifampin in inner-city AIDS patients. Am J Gastroenterol. Nov 1995;90(11):1978-80. [Medline].

  11. Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Goel RC, et al. Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N-acetylcysteine. Hum Exp Toxicol. Sep 2000;19(9):517-22. [Medline].

  12. Menzies D, Long R, Trajman A, et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Ann Intern Med. Nov 18 2008;149(10):689-97. [Medline].

  13. Kim SH, Kim SH, Bahn JW, et al. Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis. Pharmacogenomics. Nov 2009;10(11):1767-79. [Medline].

  14. Kopanoff DE, Snider DE Jr, Caras GJ. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis. Jun 1978;117(6):991-1001. [Medline].

  15. Forget EJ, Menzies D. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf. Mar 2006;5(2):231-49. [Medline].

  16. Litovitz TL, Schmitz BF, Bailey KM. 1989 annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med. Sep 1990;8(5):394-442. [Medline].

  17. Litovitz TL, Bailey KM, Schmitz BF, Holm KC, Klein-Schwartz W. 1990 annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med. Sep 1991;9(5):461-509. [Medline].

  18. Litovitz TL, Holm KC, Bailey KM, Schmitz BF. 1991 annual report of the American Association of Poison Control Centers National Data Collection System. Am J Emerg Med. Sep 1992;10(5):452-505. [Medline].

  19. Litovitz TL, Holm KC, Clancy C, Schmitz BF, Clark LR, Oderda GM. 1992 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1993;11(5):494-555. [Medline].

  20. Litovitz TL, Clark LR, Soloway RA. 1993 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1994;12(5):546-84. [Medline].

  21. Litovitz TL, Felberg L, Soloway RA, Ford M, Geller R. 1994 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1995;13(5):551-97. [Medline].

  22. Litovitz TL, Felberg L, White S, Klein-Schwartz W. 1995 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1996;14(5):487-537. [Medline].

  23. Litovitz TL, Smilkstein M, Felberg L, Klein-Schwartz W, Berlin R, Morgan JL. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1997;15(5):447-500. [Medline].

  24. Litovitz TL, Klein-Schwartz W, Dyer KS, Shannon M, Lee S, Powers M. 1997 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 1998;16(5):443-97. [Medline].

  25. Thundiyil JG, Kearney TE, Olson KR. Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System. J Med Toxicol. Mar 2007;3(1):15-9. [Medline].

  26. Stuart RL, Wilson J, Grayson ML. Isoniazid toxicity in health care workers. Clin Infect Dis. Apr 1999;28(4):895-7. [Medline].

  27. Fountain FF, Tolley E, Chrisman CR, Self TH. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest. Jul 2005;128(1):116-23. [Medline].

  28. Sullivan EA, Geoffroy P, Weisman R, Hoffman R, Frieden TR. Isoniazid poisonings in New York City. J Emerg Med. Jan-Feb 1998;16(1):57-9. [Medline].

  29. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med. Jun 1 2003;167(11):1472-7. [Medline].

  30. Romero JA, Kuczler FJ Jr. Isoniazid overdose: recognition and management. Am Fam Physician. Feb 15 1998;57(4):749-52. [Medline].

  31. Kalaci A, Duru M, Karazincir S, Sevinç TT, Kuvandik G, Balci A. Thoracic spine compression fracture during isoniazid-induced seizures: case report. Pediatr Emerg Care. Dec 2008;24(12):842-4. [Medline].

  32. Santucci KA, Shah BR, Linakis JG. Acute isoniazid exposures and antidote availability. Pediatr Emerg Care. Apr 1999;15(2):99-101. [Medline].

  33. [Guideline] Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med. Oct 15 2006;174(8):935-52. [Medline].

  34. Esfahani K, Aspler A, Menzies D, Schwartzman K. Potential cost-effectiveness of rifampin vs. isoniazid for latent tuberculosis: implications for future clinical trials. Int J Tuberc Lung Dis. Oct 2011;15(10):1340-6. [Medline].

 
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Metabolism of isoniazid.
Risk of developing overt hepatitis (%) versus age (y). Risks are much greater for older persons. Data are from a series of 13,838 patients on prophylactic isoniazid therapy reported by Kopanoff and coworkers (1978).
Risk of developing overt hepatitis versus duration of therapy. Most hepatitis presents early in the course of therapy.
Isoniazid metabolism.
Gamma-aminobutyric acid (GABA) synthesis.
 
 
 
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