• Wilson's disease is caused by a mutation in the ATP7B gene, which makes an enzyme that is involved in copper (Cu++) transport1,2
  • Cu++, which is normally eliminated through the bile ducts, accumulates in many organs, but predominately in the liver and brain1,2
  • Symptoms usually appear between the ages of 5 and 35, although patients have been diagnosed as young as 3 years of age and as old as 80 years of age1-4
  • Diagnosis is often challenging, as there is no single specific clinical or biochemical test indicative of this disease. This fact has led to the under-recognition and misdiagnosis of Wilson's disease1-3

Recognize the signs and symptoms to diagnose Wilson's disease early before liver and subsequently neurological damage occurs

Symptoms and clinical presentation vary widely

Patients with Wilson's disease may have hepatic, neurologic, and/or psychiatric symptoms in varying combinations

For younger patients, the clinical manifestations of Wilson's disease are most commonly hepatic. Children with Wilson's disease often present with chronic liver disease and abnormal liver tests.2

As patients get older, neurologic and psychiatric symptoms more commonly occur. Some common neurologic manifestations of Wilson's disease include tremor, gait abnormalities, and discoordination, dystonia, Parkinsonism, choreiform movements, drooling, dysphonia, dysarthria, and dysphasia. Behavioral and psychiatric manifestations may include depression, altered behavior and personality, impulsiveness and labile mood, sexual exhibitionism, and frank psychosis.2

Recognize these disease hallmarks for early diagnosis
and intervention

  • Presence of liver disease3-5
  • Neurological and psychiatric disorders3-5
  • Kayser-Fleischer rings3-5

    Golden-brownish pigment in cornea caused by copper deposits

  • Wilson facies3-5

    Facetious (false) smile, pseudo-laughter, open mouth and drooling saliva, reduced eye blinking and a dull look

The majority of
patients with Wilson's
disease present
symptomatically
between the ages of 5
and 35, but patients
may present at any age.
References

1. Srinivas, K. Sinha, S. Taly, A.B. et al. Dominant psychiatric manifestations in Wilson's disease: A diagnostic and therapeutic challenge. J Neurol Sci. 266 (2008) 104-108. 2. Schilsky M. Wilson Disease: Clinical Manifestations, Diagnosis, and Treatment. Clinical Liver Disease. Vol 3, No 5, May 2014. 3. Roberts EA, Schilsky ML. AASLD Practice Guidelines. Diagnosis and treatment of Wilson disease: an update. Hepatology 2008;47(6):2089-111. 4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Wilson's Disease. J Hepatol 2012;56:671-685. 5. Aggarwal A, Bhatt M. Update on Wilson disease. In Metal Related Neurodegenerative Disease, Bhatia K, Schneider S (eds.). Int Rev Neurobiol 2013;110:313-48.

Wilson's disease is a genetic disorder

Family screening is important when a patient is diagnosed with Wilson's disease. A person's risk of being a carrier or having Wilson's disease increases when his or her family has a known history of Wilson's disease. First-degree relatives must be screened for Wilson's disease.5

Screening should include:

  • liver function tests (including liver enzymes)
  • serum ceruloplasmin
  • copper concentration
  • urinary copper excretion over a 24-hour period

Some people may not know about a family history of the condition because the mutation is often passed to a child by a parent who is a carrier.5

ALL CHILDREN OF A WILSON'S DISEASE PARENT ARE AUTOMATICALLY CARRIERS OF THE DISEASE

The prevalence of Wilson's disease in the United States
is approximately 7000 - 9000 patients7
References

1. Roberts EA, Schilsky ML. AASLD Practice Guidelines. Diagnosis and treatment of Wilson disease: an update. Hepatology 2008;47(6):2089-111. 2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Wilson’s Disease. J Hepatol 2012;56:671-685. 3. Aggarwal A, Bhatt M. Update on Wilson disease. In Metal Related Neurodegenerative Disease, Bhatia K, Schneider S (eds.). Int Rev Neurobiol 2013;110:313-48. 4. Ala A, Borjigin J, Rochwarger A, Schilsky M. Wilson disease in septuagenarian siblings: raising the bar for diagnosis. Hepatology 2005;41:668-70. 5. Schilsky, M. Ala, A. Genetic Testing for Wilson Disease: Availability and Utility. Curr Gastroenterol Rep (2010) 12:57–61. 6. National Institute of Diabetes and Digestive and Kidney Diseases. Wilson Disease. https://www.niddk.nih.gov/health-information/liver-disease/wilson-disease. Accessed April 18, 2018. 7. Ferenci P, Askari F. Whom and how to screen for Wilson disease. Expert Rev. Gastroenterol. Hepatol. 8(5), 513-520 (2014).


Please visit wilsondiseasefacts.com for more information.

important safety Information

Wilson's disease (WD), the most common inherited disorder of copper metabolism, results from a failure of the copper excretory pathway. This leads to toxic accumulation of copper in the liver and eventually other organs. 1 The worldwide prevalence of WD is estimated to be one in 30,000 individuals.2

The condition can be treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body. CLOVIQUE™ (trientine hydrochloride) is a chelating agent indicated for treatment of patients with WD who are intolerant of the first-line treatment, penicillamine.3

Indications and Usage

CLOVIQUE™ may be used to treat Wilson's disease in patients who cannot take the medication penicillamine. Clinical experience with trientine hydrochloride is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defined. CLOVIQUE™ and penicillamine cannot be considered interchangeable. CLOVIQUE™ should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.

Unlike penicillamine, CLOVIQUE™ is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, trientine hydrochloride was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.

CLOVIQUE™ is not indicated for treatment of biliary cirrhosis.

Important Safety Information

  • CLOVIQUE™ is contraindicated in patients hypersensitive to CLOVIQUE™ or any components of the formulation. Patients should be observed closely for signs of possible hypersensitivity.
  • Patients receiving CLOVIQUE™ should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia.
  • The treatment can be monitored by the determination of free copper in the serum. Therapy may be monitored with a 24-hour urinary copper analysis periodically (i.e., every 6-12 months).
  • CLOVIQUE™ contains a color additive FD&C Yellow #5 (tartrazine) that may cause allergic-type reactions (including bronchial asthma) in certain people. It is frequently seen in patients who also have aspirin hypersensitivity.
  • Patients should be directed to take CLOVIQUE™ on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed. For the first month of treatment, the patient should have his temperature taken nightly, and he should be asked to report any symptom such as fever or skin eruption.
  • In general, mineral supplements should not be given since they may block the absorption of CLOVIQUE™.
  • CLOVIQUE™ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • The following adverse reactions have been reported in a clinical study using trientine hydrochloride: iron deficiency, systemic lupus erythematosus. In addition, dystonia, muscular spasm, myasthenia gravis have been reported in marketed use.
  • CLOVIQUE™ carton should be kept refrigerated at 2C - 8°C (36°F - 46°F).
  • For patient convenience, individual blister pack (or tray) may be stored for a maximum single period of 30 days at or below room temperature (25°C (77°F)) with protection from sources of heat and humidity. Capsules stored at room temperature should be discarded after 30 days.

Please see full Prescribing Information for CLOVIQUE™ Capsules.

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. You may also contact Kadmon Pharmaceuticals, LLC at 1-877-377-7862 to report negative side effects.

References:
  1. Gaffney D, Fell GS, O'Reilly DS. ACP Best Practice No 163. Wilson's disease: acute and presymptomatic laboratory diagnosis and monitoring. J Clin Pathol. 2000;53(11):807-812.

  2. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson's Disease. J Hepatol. 2012;56(3):671-685.

  3. Clovique™ Package Insert. Kadmon Pharmaceuticals, LLC 2018,

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