title: Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease.
abstract: OBJECTIVE
  To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease.
  
  
  METHODS
  A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure.
  
  
  CONCLUSIONS
  Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed.
  
  
  CONCLUSIONS
  In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: C C
authors.initials: CC
authors.lastname: Ping
authors.forename: Y
authors.initials: Y
authors.lastname: Hassan
authors.forename: N A
authors.initials: NA
authors.lastname: Aziz
authors.forename: R
authors.initials: R
authors.lastname: Ghazali
authors.forename: A
authors.initials: A
authors.lastname: Awaisu
mesh_terms: D000328:Adult; D002614:Chelating Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017809:Fatal Outcome; D005260:Female; D006527:Hepatolenticular Degeneration / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology*; D008296:Malaysia; D009965:Orphan Drug Production; D010396:Penicillamine / Q000009:adverse effects* / Q000627:therapeutic use*; D012008:Recurrence; D014131:Trace Elements / Q000600:supply & distribution; D014266:Trientine / Q000600:supply & distribution; D015032:Zinc / Q000600:supply & distribution
chemical_list: D002614:Chelating Agents; D014131:Trace Elements; D010396:Penicillamine; D015032:Zinc; D014266:Trientine