Wilson Disease Medication

  • Author: Richard K Gilroy, MBBS, FRACP; Chief Editor: Julian Katz, MD   more...
 
Updated: Mar 1, 2012
 

Medication Summary

The mainstay of therapy for Wilson disease is the use of chelating agents and medications that block copper absorption from the gastrointestinal (GI) tract.

Zinc and penicillamine are lifelong medications for patients with Wilson disease. Dosages vary with the severity of the disorder. Patients who do not respond to zinc therapy and who have increased activities of liver enzymes should be identified so that chelating agents may be added to the therapeutic regimen.[14, 15]

Other medications used to treat Wilson disease include anticholinergics, baclofen, gamma-aminobutyric acid (GABA) antagonists, and levodopa, to treat parkinsonism and dystonia symptoms; antiepileptics to treat seizures; and neuroleptics to treat psychiatric symptoms. In addition, protein restriction, lactulose, or both are used to treat hepatic encephalopathy.

Next

Chelating Agents

Class Summary

Chelating agents bind excess copper. Ammonium tetrathiomolybdate is being used under the investigational new drug approval of the US Food and Drug Administration (FDA) at the University of Michigan as an initial treatment for patients who present with neurologic or psychiatric manifestations. This drug works as a chelating agent and as an inhibitor of copper absorption from the GI tract.[16]

View full drug information

Penicillamine (Cuprimine, Depen)

 

Penicillamine forms soluble complexes with metals excreted in urine. It was the drug of choice before newer regimens were available. Because of extensive toxicities, alternative agents are used. It must be administered with pyridoxine 25 mg by mouth daily.

View full drug information

Trientine (Syprine)

 

Trientine is an effective oral chelator used to induce cupruresis. It is useful for patients who cannot tolerate penicillamine. It is indicated in Wilson disease if the initial presentation is hepatic. It should be administered with zinc.

Previous
Next

Nutrients

Class Summary

Nutrients are essential to normal growth and development, and they play a role in many metabolic processes.

View full drug information

Zinc (Orazinc, Zincate)

 

Zinc is a cofactor for more than 70 types of enzymes. It is approved for patients initially treated with a chelating agent. It should be used for maintenance after initial therapy. Zinc acetate is the drug of choice in presymptomatic, pregnant, pediatric populations, and in some instance for maintenance in compliant patients who have undergone copper chelation therapy. It is a second-line therapy in patients with neurologic manifestations who do not tolerate chelation as a consequence of deterioration on this therapy.

View full drug information

Pyridoxine (Aminoxin, Pyri-500)

 

Pyridoxine is involved in synthesis of GABA within the CNS.

View full drug information

Dimercaprol (BAL in Oil)

 

Dimercaprol is for refractory cases of Wilson disease that are not responding to first- or second-line treatment.

Previous
 
Contributor Information and Disclosures
Author

Richard K Gilroy, MBBS, FRACP  Associate Professor, Medical Director of Liver Transplantation and Hepatology, Department of Internal Medicine, Kansas University Medical Center

Disclosure: genetech, gilead, NPS pharmaceuticals Salary Speaking and teaching

Coauthor(s)

Rahil Shah, MD  Consulting Staff, Lebanon Endoscopy Center

Rahil Shah, MD is a member of the following medical societies: American College of Gastroenterology and American Society for Gastrointestinal Endoscopy

Disclosure: Takeda Consulting fee Speaking and teaching

Michael H Piper, MD, FACG, FACP  Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates PLC

Michael H Piper, MD, FACG, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, and Michigan State Medical Society

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

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 American Society of Human Genetics

Disclosure: Nothing to disclose.

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Beth A Carter, MD Assistant Professor of Pediatrics, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine; Medical Director, Pediatric Intestinal Rehabilitation Program, Texas Children's Hospital

Beth A Carter, MD is a member of the following medical societies: American Gastroenterological Association, American Liver Foundation, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Robert J Fingerote, MD, MSc, FRCPC Consultant, Clinical Evaluation Division, Biologic and Gene Therapies, Directorate Health Canada; Consulting Staff, Department of Medicine, Division of Gastroenterology, York Central Hospital, Ontario

Robert J Fingerote, MD, MSc, FRCPC is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada

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

References

  1. Schilsky ML. Wilson disease: Current status and the future. Biochimie. Jul 30 2009;[Medline].

  2. Bowcock AM, Farrer LA, Hebert JM, Agger M, Sternlieb I, Scheinberg IH, et al. Eight closely linked loci place the Wilson disease locus within 13q14-q21. Am J Hum Genet. Nov 1988;43(5):664-74. [Medline]. [Full Text].

  3. Stapelbroek JM, Bollen CW, van Amstel JK, et al. The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis. J Hepatol. Nov 2004;41(5):758-63. [Medline].

  4. Stuehler B, Reichert J, Stremmel W, Schaefer M. Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med (Berl). Sep 2004;82(9):629-34. [Medline].

  5. Merle U, Schaefer M, Ferenci P, Stremmel W. Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut. Jan 2007;56(1):115-20. [Medline]. [Full Text].

  6. Manolaki N, Nikolopoulou G, Daikos GL, Panagiotakaki E, Tzetis M, Roma E, et al. Wilson disease in children: analysis of 57 cases. J Pediatr Gastroenterol Nutr. Jan 2009;48(1):72-7. [Medline].

  7. Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. Jun 2008;47(6):2089-111. [Medline].

  8. Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation. Transplantation. Jan 27 2009;87(2):261-7. [Medline].

  9. Walshe JM. Copper: its role in the pathogenesis of liver disease. Semin Liver Dis. Aug 1984;4(3):252-63. [Medline].

  10. Dastych M, Prochazkova D, Pokorny A, Zdrazil L. Copper and zinc in the serum, urine, and hair of patients with Wilson's disease treated with penicillamine and zinc. Biol Trace Elem Res. Jun 27 2009;epub ahead of print. [Medline].

  11. Soni D, Shukla G, Singh S, Goyal V, Behari M. Cardiovascular and sudomotor autonomic dysfunction in Wilson's disease-Limited correlation with clinical severity. Auton Neurosci. Aug 7 2009;epub ahead of print. [Medline].

  12. Tarnacka B, Szeszkowski W, Golebiowski M, Czlonkowska A. Metabolic changes in 37 newly diagnosed Wilson's disease patients assessed by magnetic resonance spectroscopy. Parkinsonism Relat Disord. Sep 2009;15(8):582-6. [Medline].

  13. Sen S, Felldin M, Steiner C, et al. Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease. Liver Transpl. Oct 2002;8(10):962-7. [Medline].

  14. Weiss KH, Gotthardt DN, Klemm D, Merle U, Ferenci-Foerster D, Schaefer M, et al. Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease. Gastroenterology. Apr 2011;140(4):1189-1198.e1. [Medline].

  15. da Costa Mdo D, Spitz M, Bacheschi LA, Leite CC, Lucato LT, Barbosa ER. Wilson's disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI. Neuroradiology. Oct 2009;51(10):627-33. [Medline].

  16. Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, et al. Treatment of Wilson's disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a comparison with trientine. Transl Res. Aug 2009;154(2):70-7. [Medline].

 
Previous
Next
 
Computed tomography (CT) scan in a 15-year-old boy who presented with central nervous system findings consistent with Wilson disease. The CT scan reveals hypodense regions in the basal ganglia (caudate nucleus, putamen, globus pallidus). The differential diagnosis based on this image alone included leukodystrophy, vasculitis, and, less likely, infection. Ventricular enlargement and posterior fossa atrophy may also be seen on brain CT scans in a patient with Wilson disease. The extent of involvement as depicted on CT scans does not provide prognostic information.
Approach to the diagnosis of Wilson disease (WD) in a patient with unexplained liver disease. KF = Kayser-Fleischer ring; CPN = ceruloplasmin. From the American Association for the Study of Liver Diseases Practice Guidelines.
In this particular case, there is abundant Mallory hyaline. Another notable finding is the moderate to marked chronic inflammation which involved most portal tracts and periportal/perinodular areas.
Prismaflex eXeed II adds citrate anticoagulation with integrated calcium management. Image courtesy of Gambro.
Molecular adsorbents recirculating system (MARS) circuit.
Biopsy specimen showing hepatocellular injury in an explant specimen from a patient transplanted for Wilson Disease.
Biopsy specimen showing a more detailed image of the cellular injury in acute Wilson disease.
Wilson disease biopsy specimen with rhodanine stain.
Wilson disease biopsy specimen with rhodanine stain (stain specific for copper deposition).
Table. Prognostic Index in Fulminant Wilsonian Hepatitis
Score01234
Serum bilirubin (reference range, 3-20 mmol/L)< 100100-150151-200201-300>300
Serum aspartate transaminase (reference range, 7-40 IU/L)< 100100-150151-200201-300>300
Prothrombin time prolongation (seconds)< 44-89-1213-20>30
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.