• Wilson's disease is caused by a mutation in the ATP7B gene, which makes an enzyme that is involved in copper (Cu++) transport2,5,6
  • Cu++, which is normally eliminated through the bile ducts, accumulates in many organs, but predominately in the liver and brain2,6
  • Symptoms usually appear between the ages of 5 and 356; although patients have been diagnosed as young as age 3 and as old as age 803,4,7,8
  • Diagnosis is often challenging, as there is no single specific clinical or biochemical test indicative of this disease.9 This fact has led to the underrecognition and misdiagnosis of Wilson's disease2,3,8

Recognize the signs and symptoms of Wilson's disease to help with early diagnosis before patients sustain liver and subsequent neurologic damage2,3,8

Symptoms and clinical presentation vary widely3-5

Patients with Wilson's disease may have hepatic, neurologic and/or psychiatric symptoms in varying combinations3-5

For younger patients, the clinical manifestations of Wilson's disease are mostly hepatic. Children with Wilson's disease often present with chronic liver disease and abnormal liver tests.10

As patients get older, neurologic and psychiatric symptoms occur more frequently.10 Some of the common neurologic manifestations of Wilson's disease include tremor, gait abnormalities, discoordination, dystonia, Parkinsonism, choreiform movements, drooling, dysphonia, dysarthria and dysphagia. Behavioral and psychiatric manifestations may include depression, altered behavior and personality, impulsiveness and labile mood, sexual exhibitionism and frank psychosis.4,10

Recognize these disease hallmarks for early diagnosis
and intervention

  • Presence of liver disease3,4
  • Neurologic and psychiatric disorders3,4
  • Kayser-Fleischer rings4

    Golden-brown pigment in cornea caused by copper deposits11

  • Wilson facies5

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

Most patients with Wilson's disease present symptomatically between the ages of 5 and 35; however, patients may present at any age.6

Wilson's disease is a genetic disorder1

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.3,12

Screening should include4

  • 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.13

ALL CHILDREN OF A PARENT WITH WILSON'S DISEASE ARE CARRIERS OF THE DISEASE10

The prevalence of Wilson's disease in the United States
is approximately 7000 to 9000 patients9
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References

1. Olivarez L, Caggana M, Pass KA, Ferguson P, Brewer GJ. Estimate of the frequency of Wilson's disease in the US Caucasian population: a mutation analysis approach. Ann Hum Genet . 2001;65(Pt 5):459-463. doi:10.1017/S0003480001008764 2. Zimbrean PC, Schilsky ML. Psychiatric aspects of Wilson disease: a review. Gen Hosp Psychiatry. 2014;36(1):53-62. doi:10.1016/j.genhosppsych.2013.08.007 3. Hedera P. Update on the clinical management of Wilson's disease. Appl Clin Genet. 2017;10:9-19. doi:10.2147/TACG.S79121 4. Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-2111. doi:10.1002/hep.22261 5. Aggarwal A, Bhatt M. Update on Wilson disease. Int Rev Neurobiol. 2013;110:313-348. doi:10.1016/B978-0-12-410502-7.00014-4 6.Patil M, Sheth KA, Krishnamurthy AC, Devarbhavi H. A review and current perspective on Wilson disease. J Clin Exp Hepatol. 2013;3(4):321-336. doi:10.1016/j.jceh.2013.06.002 7.Millard H, Zimbrean P, Martin A. Delay in diagnosis of Wilson disease in children with insidious psychiatric symptoms: a case report and review of the literature. Psychosomatics. 2015;56(6):700-705. doi:10.1016/j.psym.2015.07.008 8. Srinivas K, Sinha S, Taly AB, et al. Dominant psychiatric manifestations in Wilson's disease: a diagnostic and therapeutic challenge! J Neurol Sci. 2008;266(1-2):104-108. doi:10.1016/j.jns.2007.09.009 9. Ferenci P. Whom and how to screen for Wilson disease. Expert Rev Gastroenterol Hepatol. 2014;8(5):513-520. doi:10.1586/17474124.2014.899898 10. Schilsky ML. Wilson disease: clinical manifestations, diagnosis, and treatment. Clin Liver Dis (Hoboken). 2014;3(5):104-107. doi:10.1002/cld.349 11. Joshi G, Dhingra D, Tekchandani U, Kaushik S. Kayser-Fleischer ring in Wilson's disease. QJM. 2019;112(8):629. doi:10.1093/qjmed/hcz027 12. Inheritance. Wilson Disease Association. Accessed April 9, 2020. https://www.wilsondisease.org/about-wilson-disease/inheritance 13. Schilsky ML, Ala A. Genetic testing for Wilson disease: availability and utility. Curr Gastroenterol Rep. 2010;12(1):57-61. doi:10.1007/s11894-009-0084-5

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. CLOVIQUETM (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

CLOVIQUETM 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. CLOVIQUETM and penicillamine cannot be considered interchangeable. CLOVIQUETM should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.

Unlike penicillamine, CLOVIQUETM 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.

CLOVIQUETM is not indicated for treatment of biliary cirrhosis.

Important Safety Information

  • CLOVIQUETM is contraindicated in patients hypersensitive to CLOVIQUETM or any components of the formulation. Patients should be observed closely for signs of possible hypersensitivity.
  • Patients receiving CLOVIQUETM 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).
  • CLOVIQUETM 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 CLOVIQUETM 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 CLOVIQUETM.
  • CLOVIQUETM 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.
  • CLOVIQUETM carton should be kept refrigerated at 2°C - 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 CLOVIQUETM 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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