Trientine is a highly hygroscopic molecule and increased water absorption could lead to degradation of trientine hydrochloride (HCl) capsules. An in-use real-world stability study for trientine HCl capsules stored in a bottle demonstrated nearly 2x the water accumulation when compared to CLOVIQUE™ blister packaging. The differences in water accumulation observed over 63 days were in spite of the bottled capsules being evaluated under refrigeration (2°C – 8°C) while the blister pack capsules were evaluated at higher temperatures (25°C, 30°C, 40°C) to simulate a real-world, variable room temperature environment. CLOVIQUE™ individual blister packaged capsules are preserved in a unit dose protected from air and humidity and therefore, were reported to have lower water absorption.*

*Data on file.

CLOVIQUE™
Room Temperature Stable Blister Pack

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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,

©2018 Kadmon Pharmaceuticals, Inc.

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