Wilson disease: Children and Adolescents: Oral: Initial: 20 mg/kg/day (round dose to the nearest 250 mg) in 2 to 3 divided doses; maximum initial daily dose: 1,000 mg/day; titrate dose based on clinical response and free serum copper (non-ceruloplasmin bound copper) concentrations and/or 24-hour urinary copper excretion; usual maintenance dose: 900 to 1,500 mg/day in 2 to 3 divided doses (AASLD [Roberts 2008]; EASL 2012; ESPGHAN [Socha 2018]).
Maximum daily dose:
Children: 1,500 mg/day (AASLD [Roberts 2008]; EASL 2012; ESPGHAN [Socha 2018])
Adolescents: 2,000 mg/day
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Trientine: Drug information")
Wilson disease: Oral: Initial: 750 to 1,250 mg/day in divided doses 2 to 4 times daily; increase dose if clinical response not adequate or the concentration of free serum copper is persistently >20 mcg/dL; maximum dose: 2,000 mg/day. AASLD practice guidelines suggest typical doses of 750 to 1,500 mg/day in 2 to 3 divided doses with maintenance therapy of 750 to 1,000 mg/day (AASLD [Roberts 2008]). Optimal long-term maintenance dosage should be determined at 6- to 12-month intervals.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Clovique: 250 mg [DSC]
Syprine: 250 mg
Generic: 250 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 250 mg
Cuvrior tablets: FDA approved April 2022; availability anticipated in the third quarter of 2022. Information pertaining to this product within the monograph is pending revision. Cuvrior is indicated for the treatment of adult patients with stable Wilson’s disease who are de-coppered and tolerant to penicillamine. Consult the prescribing information for additional information.
Oral: Administer on an empty stomach at least 1 hour before or at least 2 hours after meals and at least 1 hour apart from any other drug, food, or milk; however, administration closer to meals may be considered if it improves adherence (AASLD [Roberts 2008]; EASL 2012; manufacturer's labeling). Swallow capsule whole with water; do not chew or open capsule. Any skin exposed to the contents of a capsule should be promptly washed with water.
Oral: Administer at least1 hour before or 2 hours after meals and at least 1 hour apart from any drug, food, or milk. Do not open or chew capsule, swallow whole with water; any skin exposed to the contents of a capsule should be promptly washed with water. May be taken closer to meals if needed to improve adherence (AASLD [Roberts 2008]; EASL 2012).
Store at 2°C to 8°C (36°F to 46°F). Note: Although an AB rated generic to Syprine, the manufacturer's labeling for Dr. Reddy's generic capsules states to store at 20°C to 25°C (68°F to 77°F).
Additional product-specific storage information: Clovique: Individual blister pack (or tray) may be stored for a maximum single period of 30 days at or below 25ºC (77ºF); protect from heat and humidity.
Treatment of Wilson disease in patients intolerant to penicillamine (FDA approved in ages ≥6 years and adults).
Trientine may be confused with TRENtal®, tretinoin
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Central nervous system: Dystonia, myasthenia gravis, neurological deterioration (worsening; European Association for the Study of the Liver 2012)
Endocrine & metabolic: Iron deficiency
Gastrointestinal: Gastritis (Roberts 2008)
Hypersensitivity: Fixed drug eruption (Roberts 2008)
Neuromuscular & skeletal: Muscle spasm, systemic lupus erythematosus
<1%, postmarketing, and/or case reports: Aplastic anemia (Roberts 2008), pancytopenia (Roberts 2008), sideroblastic anemia (reversible; Roberts 2008)
Hypersensitivity to trientine or any component of the formulation.
Concerns related to adverse effects:
• Anemia: May cause iron-deficiency anemia; monitor closely, especially in females.
• Copper deficiency: Induced by treatment; may lead to hepatic iron overload and/or sideroblastic anemia; reassess dose (AASLD [Roberts 2008]).
• Neurologic worsening: May occur with treatment initiation; less common than with penicillamine (AASLD [Roberts 2008]).
Other warnings/precautions:
• Hypersensitivity: Not reported with use; however, industrial workers exposed to trientine for prolonged periods have reported asthma, bronchitis, and dermatitis.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Polyvalent Cation Containing Products: May decrease the serum concentration of Trientine. Management: Avoid concomitant use of trientine and polyvalent cations. If oral iron supplements are required, separate the administration by 2 hours. For other oral polyvalent cations, give trientine 1 hour before, or 1 to 2 hours after the polyvalent cation. Risk D: Consider therapy modification
Food, dairy products, or other sources of polyvalent cations will be chelated by trientine. Management: Should be taken 1 hour before or 2 hours after meals and at least 1 hour apart from any drug, food, or milk. May be taken closer to meals if needed to improve adherence (AASLD [Roberts 2008]; EASL 2012).
Should be taken 1 hour before or 2 hours after meals and at least 1 hour apart from any drug, food, or milk.
Treatment of Wilson disease should be maintained during pregnancy; dose reduction (25% to 50% of prepregnancy dose) should be considered (AASLD [Roberts 2008]).
Periodic 24-hour urinary copper assessment (at least yearly; more frequently until stable, if dose is adjusted, or if there is a question of compliance); serum non-ceruloplasmin bound copper; physical exam, LFTs, CBC, INR, and urinalysis (weekly during initiation, then every 1 to 3 months until remission, followed by every 3 to 6 months); periodic ophthalmic exam (AASLD [Roberts 2008]; EASL 2012); fever and skin changes during the first month of therapy
Adequate treatment: Serum non-ceruloplasmin bound copper <15 mcg/dL (Serum non-ceruloplasmin bound copper = Total copper - ceruloplasmin copper); 24-hour urinary copper excretion 200 to 500 mcg (3 to 8 micromoles)/day (AASLD [Roberts 2008]; ESPGHAN [Socha 2018])
Trientine is an oral chelating agent structurally dissimilar from penicillamine and other available chelating agents; an effective oral chelator of copper used to induce adequate cupriuresis
Absorption: Poor (AASLD [Roberts 2008]).
Metabolism: To acetyltrien (chelating activity significantly less than parent) (AASLD [Roberts 2008]).
Excretion: Urine (1% as parent; 8% as metabolite) (AASLD [Roberts 2008]).
Capsules (Syprine Oral)
250 mg (per each): $255.20
Capsules (Trientine HCl Oral)
250 mg (per each): $229.43 - $242.44
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