About Wilson's Disease

What Is Wilson’s Disease?

Wilson’s disease (WD) is a genetic disease that prevents the body from metabolizing copper, which then builds up to toxic levels in the liver, brain, and/or other organs.1 Copper is an essential metal. It is an important cofactor for many proteins, and is vital to the development and maintenance of the central nervous system.2 However, the average diet contains more copper than the body needs: typical intake is 2–5 mg/d, while the recommended intake is 0.9 mg/d.1 The liver processes the necessary amount and excretes what is left over.1
  • WD is a rare disease, with a US prevalence of approximately 11,000 cases
  • Worldwide, an average of 30 individuals per million are affected1
  • More than 500 different mutations can cause WD, but all of them affect the gene ATP7B, which can be found on chromosome 13 in human cells1,3
  • This gene produces the copper transporting P-type ATPase (ATP7B) protein, which is necessary for the removal of copper from the body1
  • The mutations causing defective function of ATP7B are autosomal recessive4
WD is fatal if left untreated.1 Its diagnosis is often overlooked due to the multisystem protean manifestations of the disease.5,6 Diagnosis will require a liver biopsy, with other tests available to help confirm the diagnosis.1 WD can be treated effectively with a low copper diet and chelating agents.7
 
References
  1. Roberts EA, Schilsky ML. AASLD Practice Guidelines. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-2111.
  2. Desai V, Kaler SG. Role of copper in human neurological disorders. Am J Clin Nutr. 2008;88(suppl):855S-858S.
  3. Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC. Wilson’s disease: a review of what we have learned. World J Hepatol. 2015;7(29):2859-2870.
  4. National Institute of Diabetes and Digestive and Kidney Diseases. Wilson Disease. http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/wilson-disease/Pages/facts.aspx#sec10. Accessed May 25, 2016.
  5. Basu D, Gangopadhyay PK. Wilson’s disease: aspects of diagnosis and treatment. J Assoc Physicians India. 2015;63(5):94.
  6. Lin L, Wang D, Ding N, Zheng C. Hepatic manifestations in Wilson’s disease: report of 110 cases. Hepatogastroenterology. 2015;62(139):657-660.
  7. Wilson Disease Association. Diet and nutrition. http://www.wilsonsdisease.org/wilson-disease/wilsondisease-diet.php. Accessed July 1, 2016.
Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity.

INDICATION

CUPRIMINE® (Penicillamine) is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that CUPRIMINE® is not of value in ankylosing spondylitis.

IMPORTANT SAFETY INFORMATION

  • Except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Mothers on therapy with penicillamine should not nurse their infants.
  • Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency.
  • The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis.
  • Routine urinalysis, white and differential blood cell count, hemoglobin determination, direct platelet count, together with monitoring of the patient's skin, lymph nodes and body temperature, must be done twice weekly for five months and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding.
  • A reduction in WBC count below 3500/mm3 requires discontinuation. Platelet count below 100,000/mm3 even in absence of clinical bleeding; or a progressive fall in either platelet or WBC count in three successive determinations requires at least temporary cessation of therapy.
  • Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome.
  • Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy. In Wilson's disease, these are recommended every three months, at least during the first year of treatment.
  • Onset of new or worsening of existing neurological symptoms has been reported during initiation of therapy with CUPRIMINE®.
  • When pemphigus is suspected, CUPRIMINE® should be discontinued.
  • Pregnancy Category D - Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine should not be administered to pregnant women with cystinuria or rheumatoid arthritis and should be discontinued promptly in patients in whom pregnancy is suspected or diagnosed. Penicillamine has been shown to be teratogenic in rats when given doses 6 times higher than the highest dose recommended for humans.
  • Penicillamine for Wilson’s disease should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Reported experience shows that continued treatment with penicillamine throughout pregnancy protects the mother against relapse of the Wilson's disease, and discontinuation of penicillamine has deleterious effects on the mother, which may be fatal.
  • Some patients may experience drug fever with or without macular cutaneous eruptions. Penicillamine should be temporarily discontinued in these patients if being treated for Wilson's disease or cystinuria until the reaction subsides. In the case of drug fever in rheumatoid arthritis patients, because other treatments are available, penicillamine should be discontinued.
  • The skin and mucous membranes should be observed for allergic reactions. Early and late rashes have occurred. Less commonly, a late rash may be seen, usually after six months or more of treatment, and requires discontinuation of penicillamine.
  • The appearance of a drug eruption accompanied by fever, arthralgia, lymphadenopathy or other allergic manifestations usually requires discontinuation of penicillamine.
  • Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone because these drugs are also associated with similar serious hematologic and renal adverse reactions. Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine but not necessarily of the same type.
  • Patients who are allergic to penicillin may theoretically have cross-sensitivity to penicillamine.
  • Patients with Wilson's disease or cystinuria should be given 25 mg/day of pyridoxine during therapy, since penicillamine increases the requirement for this vitamin. Patients also may receive benefit from a multivitamin preparation. In Wilson's disease, multivitamin preparations must be copper-free. Rheumatoid arthritis patients whose nutrition is impaired should also be given a daily supplement of pyridoxine. Mineral supplements should not be given, since they may block the response to penicillamine.
  • Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal.
  • Reported incidences for the most commonly occurring adverse reactions in rheumatoid arthritis patients based on 17 representative clinical trials reported in the literature (1270 patients) include events related to Allergy: pruritis, rashes, pemphigus; Gastrointestinal: anorexia, epigastric pain, nausea, vomiting, or occasional diarrhea, hepatic dysfunction, effect on taste perception and oral ulcerations; Hematological: leukopenia, thrombocytopenia leading to fatalities; Renal: proteinuria and/or hematuria progressing to nephrotic syndrome, renal failure; Central Nervous System: tinnitus, optic neuritis, peripheral sensory and motor neuropathies, muscular weakness, visual and psychic disturbances, mental disorders, and agitation and anxiety; Neuromuscular: myasthenia gravis, dystonia. Other: Adverse reactions reported rarely include thrombophlebitis, hyperpyrexia, alopecia, lichen planus, polymyositis, dermatomyositis, mammary hyperplasia, elastosis perforans serpiginosa, toxic epidermal necrolysis, anetoderma, and Goodpasture's syndrome. Vasculitis, including fatal renal vasculitis, allergic alveolitis, obliterative bronchiolitis, interstitial pneumonitis, pulmonary fibrosis, and bronchial asthma also has been reported.
Please click here to see full Prescribing Information for CUPRIMINE® capsules.
 

©2016 Valeant Pharmaceuticals North America LLC. All Rights Reserved. CUP.0031.USA.16

 

INDICATIONS

Cuprimine® (Penicillamine) is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that Cuprimine is not of value in ankylosing spondylitis.

IMPORTANT SAFETY INFORMATION

Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity.

  • Except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Mothers on therapy with penicillamine should not nurse their infants.
  • Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency.
  • The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis.
  • Routine urinalysis, white and differential blood cell count, hemoglobin determination, direct platelet count, together with monitoring of the patient's skin, lymph nodes and body temperature, must be done twice weekly for five months and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding.
  • A reduction in WBC count below 3500/mm3 requires discontinuation. Platelet count below 100,000/mm3 even in absence of clinical bleeding; or a progressive fall in either platelet or WBC count in three successive determinations requires at least temporary cessation of therapy.
  • Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome.
  • Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy. In Wilson's disease, these are recommended every three months, at least during the first year of treatment.
  • Onset of new or worsening of existing neurological symptoms has been reported during initiation of therapy with Cuprimine.
  • When pemphigus is suspected, Cuprimine should be discontinued.
  • Pregnancy Category D - Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine should not be administered to pregnant women with cystinuria or rheumatoid arthritis and should be discontinued promptly in patients in whom pregnancy is suspected or diagnosed. Penicillamine has been shown to be teratogenic in rats when given doses 6 times higher than the highest dose recommended for humans. enicillamine for Wilson’s disease should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Reported experience shows that continued treatment with penicillamine throughout pregnancy protects the mother against relapse of the Wilson's disease, and discontinuation of penicillamine has deleterious effects on the mother, which may be fatal.
  • Some patients may experience drug fever with or without macular cutaneous eruptions. Penicillamine should be temporarily discontinued in these patients if being treated for Wilson's disease or cystinuria until the reaction subsides. In the case of drug fever in rheumatoid arthritis patients, because other treatments are available, penicillamine should be discontinued.
  • The skin and mucous membranes should be observed for allergic reactions. Early and late rashes have occurred. Less commonly, a late rash may be seen, usually after six months or more of treatment, and requires discontinuation of penicillamine.
  • The appearance of a drug eruption accompanied by fever, arthralgia, lymphadenopathy or other allergic manifestations usually requires discontinuation of penicillamine.
  • Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone because these drugs are also associated with similar serious hematologic and renal adverse reactions. Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine but not necessarily of the same type.
  • Patients who are allergic to penicillin may theoretically have cross-sensitivity to penicillamine.
  • Patients with Wilson's disease or cystinuria should be given 25 mg/day of pyridoxine during therapy, since penicillamine increases the requirement for this vitamin. Patients also may receive benefit from a multivitamin preparation. In Wilson's disease, multivitamin preparations must be copper-free. Rheumatoid arthritis patients whose nutrition is impaired should also be given a daily supplement of pyridoxine. Mineral supplements should not be given, since they may block the response to penicillamine.
  • Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal.
  • Reported incidences for the most commonly occurring adverse reactions in rheumatoid arthritis patients based on 17 representative clinical trials reported in the literature (1270 patients) include events related to Allergy: pruritis, rashes, pemphigus; Gastrointestinal: anorexia, epigastric pain, nausea, vomiting, or occasional diarrhea, hepatic dysfunction, effect on taste perception and oral ulcerations; Hematological: leukopenia, thrombocytopenia leading to fatalities; Renal: proteinuria and/or hematuria progressing to nephrotic syndrome, renal failure; Central Nervous System: tinnitus, optic neuritis, peripheral sensory and motor neuropathies, muscular weakness, visual and psychic disturbances, mental disorders, and agitation and anxiety; Neuromuscular: myasthenia gravis, dystonia. Other: Adverse reactions reported rarely include thrombophlebitis, hyperpyrexia, alopecia, lichen planus, polymyositis, dermatomyositis, mammary hyperplasia, elastosis perforans serpiginosa, toxic epidermal necrolysis, anetoderma, and Goodpasture's syndrome. Vasculitis, including fatal renal vasculitis, allergic alveolitis, obliterative bronchiolitis, interstitial pneumonitis, pulmonary fibrosis, and bronchial asthma also has been reported.
Please click here to see full Prescribing Information for Cuprimine capsules.
 

INDICATIONS

Cuprimine® (Penicillamine) is indicated in the treatment of Wilson's disease, cystinuria, and in patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Available evidence suggests that Cuprimine is not of value in ankylosing spondylitis.

IMPORTANT SAFETY INFORMATION

Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations, and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity.

  • Except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Mothers on therapy with penicillamine should not nurse their infants.
  • Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency.
  • The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis.
  • Routine urinalysis, white and differential blood cell count, hemoglobin determination, direct platelet count, together with monitoring of the patient's skin, lymph nodes and body temperature, must be done twice weekly for five months and monthly thereafter. Patients should be instructed to report promptly the development of signs and symptoms of granulocytopenia and/or thrombocytopenia such as fever, sore throat, chills, bruising or bleeding.
  • A reduction in WBC count below 3500/mm3 requires discontinuation. Platelet count below 100,000/mm3 even in absence of clinical bleeding; or a progressive fall in either platelet or WBC count in three successive determinations requires at least temporary cessation of therapy.
  • Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to a nephrotic syndrome.
  • Because of rare reports of intrahepatic cholestasis and toxic hepatitis, liver function tests are recommended every six months for the duration of therapy. In Wilson's disease, these are recommended every three months, at least during the first year of treatment.
  • Onset of new or worsening of existing neurological symptoms has been reported during initiation of therapy with Cuprimine.
  • When pemphigus is suspected, Cuprimine should be discontinued.
  • Pregnancy Category D - Penicillamine can cause fetal harm when administered to a pregnant woman. Penicillamine should not be administered to pregnant women with cystinuria or rheumatoid arthritis and should be discontinued promptly in patients in whom pregnancy is suspected or diagnosed. Penicillamine has been shown to be teratogenic in rats when given doses 6 times higher than the highest dose recommended for humans. enicillamine for Wilson’s disease should be used in women of childbearing potential only when the expected benefits outweigh the possible hazards. Reported experience shows that continued treatment with penicillamine throughout pregnancy protects the mother against relapse of the Wilson's disease, and discontinuation of penicillamine has deleterious effects on the mother, which may be fatal.
  • Some patients may experience drug fever with or without macular cutaneous eruptions. Penicillamine should be temporarily discontinued in these patients if being treated for Wilson's disease or cystinuria until the reaction subsides. In the case of drug fever in rheumatoid arthritis patients, because other treatments are available, penicillamine should be discontinued.
  • The skin and mucous membranes should be observed for allergic reactions. Early and late rashes have occurred. Less commonly, a late rash may be seen, usually after six months or more of treatment, and requires discontinuation of penicillamine.
  • The appearance of a drug eruption accompanied by fever, arthralgia, lymphadenopathy or other allergic manifestations usually requires discontinuation of penicillamine.
  • Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone because these drugs are also associated with similar serious hematologic and renal adverse reactions. Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine but not necessarily of the same type.
  • Patients who are allergic to penicillin may theoretically have cross-sensitivity to penicillamine.
  • Patients with Wilson's disease or cystinuria should be given 25 mg/day of pyridoxine during therapy, since penicillamine increases the requirement for this vitamin. Patients also may receive benefit from a multivitamin preparation. In Wilson's disease, multivitamin preparations must be copper-free. Rheumatoid arthritis patients whose nutrition is impaired should also be given a daily supplement of pyridoxine. Mineral supplements should not be given, since they may block the response to penicillamine.
  • Penicillamine is a drug with a high incidence of untoward reactions, some of which are potentially fatal.
  • Reported incidences for the most commonly occurring adverse reactions in rheumatoid arthritis patients based on 17 representative clinical trials reported in the literature (1270 patients) include events related to Allergy: pruritis, rashes, pemphigus; Gastrointestinal: anorexia, epigastric pain, nausea, vomiting, or occasional diarrhea, hepatic dysfunction, effect on taste perception and oral ulcerations; Hematological: leukopenia, thrombocytopenia leading to fatalities; Renal: proteinuria and/or hematuria progressing to nephrotic syndrome, renal failure; Central Nervous System: tinnitus, optic neuritis, peripheral sensory and motor neuropathies, muscular weakness, visual and psychic disturbances, mental disorders, and agitation and anxiety; Neuromuscular: myasthenia gravis, dystonia. Other: Adverse reactions reported rarely include thrombophlebitis, hyperpyrexia, alopecia, lichen planus, polymyositis, dermatomyositis, mammary hyperplasia, elastosis perforans serpiginosa, toxic epidermal necrolysis, anetoderma, and Goodpasture's syndrome. Vasculitis, including fatal renal vasculitis, allergic alveolitis, obliterative bronchiolitis, interstitial pneumonitis, pulmonary fibrosis, and bronchial asthma also has been reported.
Please click here to see full Prescribing Information for Cuprimine capsules.