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Tyrosinemia Medication

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Aug 13, 2015
 

Medication Summary

In addition to dietary treatment, appropriate medical therapy involves the use of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a highly potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase.

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Tyrosine Degradation Inhibitor

Class Summary

NTBC prevents the formation of fumarylacetoacetate from tyrosine. Results from an international study initiated in 1992 resulted in the US Food and Drug Administration (FDA) approving the drug in January 2002.

An open-label study of 207 patients (aged 0-21.7 y; median age, 9 mo) showed a dramatic improvement in overall survival for patients younger than 2 months who presented with hereditary tyrosinemia type I and who were treated with nitisinone and dietary restriction, as compared with historical control subjects (29% vs 88% survival probabilities at 2 and 4 y).[15]

Nitisinone (Orfadin)

 

Adjunct to dietary restrictions to treat hereditary tyrosinemia type-1. Highly potent reversible inhibitor of 4-hydroxyphenylpyruvate dioxygenase. Prevents formation of catabolic intermediates from tyrosine (ie, maleylacetoacetate, fumarylacetoacetate) that are converted to toxic metabolites (ie, succinylacetone, succinyl acetoacetate) and that are responsible for observed liver and kidney toxicity.

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Contributor Information and Disclosures
Author

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

References
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