Wilson disease (alternative agent): Note: Trientine hydrochloride capsules (Clovique and generics, Syprine) are not substitutable on a mg-per-mg basis with trientine tetrahydrochloride tablets (Cuvrior) due to differences in bioavailability and amount of trientine base in each formulation (AASLD [Schilsky 2022]; Mohr 2023; manufacturer’s labeling).
Trientine hydrochloride capsules (Clovique and generics, Syprine): Oral: Initial: 750 to 1,250 mg/day or 15 to 20 mg/kg/day in 2 to 4 divided doses (AASLD [Schilsky 2022]; manufacturer's labeling). Increase dose over a 2- to 3-week period based on clinical response up to a maximum of 2 g/day; usual maintenance dose: 10 to 15 mg/kg/day in 2 to 3 divided doses (AASLD [Schilsky 2022]).
Trientine tetrahydrochloride tablets (Cuvrior):
Initial dosage (patients switching from penicillamine): Oral: Discontinue penicillamine and initiate trientine tetrahydrochloride at 300 to 3,000 mg/day in 2 equally divided doses based on penicillamine total daily dose according to the table below.
Current penicillamine total daily dosage |
Initial trientine tetrahydrochloride (Cuvrior) total daily dosagea |
---|---|
a Total daily dose should be divided equally into 2 doses; if the number of tablets cannot be equally divided between doses, then administer the higher dose in the morning and the lower dose in the evening. | |
125 mg/day |
300 mg/day |
250 mg/day |
600 mg/day |
375 mg/day |
900 mg/day |
500 mg/day |
900 mg/day |
625 mg/day |
1,200 mg/day |
750 mg/day |
1,500 mg/day |
875 mg/day |
1,800 mg/day |
1,000 mg/day |
2,100 mg/day |
1,125 mg/day |
2,400 mg/day |
1,375 mg/day |
2,700 mg/day |
≥1,500 mg/day |
3,000 mg/day |
Dosage titration: Adjust total daily dose based on clinical response up to a maximum of 3 g/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing. Use with caution; initiate at lower end of the dosing range.
(For additional information see "Trientine: Pediatric drug information")
Note: Trientine is available in 2 formulations; the trientine hydrochloride capsule (Clovique and generics, Syprine) and trientine tetrahydrochloride tablet (Cuvrior) are not bioequivalent due to differences in amount of trientine base delivered per dose and bioavailability (AASLD [Schilsky 2022]; Mohr 2023; manufacturer's labeling). Dosing is product specific; use caution; the tetrahydrochloride tablets (Cuvrior) are only approved in adults.
Wilson disease: Children and Adolescents: Trientine hydrochloride capsules (Clovique and generics, Syprine): 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: 10 to 15 mg/kg/day or 900 to 1,500 mg/day in 2 to 3 divided doses (AASLD [Schilsky 2022]; EASL 2012; ESPGHAN [Socha 2018]).
Maximum daily dose:
Children: 1,500 mg/day.
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.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash
Gastrointestinal: Abdominal pain, change in bowel habits (including abnormal stools, constipation, and soft stools)
1% to 10%:
Dermatologic: Alopecia
Hematologic: Anemia
Nervous system: Emotional lability
Frequency not defined:
Endocrine & metabolic: Iron deficiency
Neuromuscular & skeletal: Systemic lupus erythematosus
Postmarketing:
Dermatologic: Fixed drug eruption (Roberts 2008)
Gastrointestinal: Colitis (Boga 2015), gastritis (Roberts 2008)
Hematologic & oncologic: Aplastic anemia (Roberts 2008), pancytopenia (Roberts 2008), sideroblastic anemia (reversible) (Roberts 2008)
Nervous system: Myasthenia gravis, neurological deterioration (worsening) (European Association for the Study of the Liver 2012)
Neuromuscular & skeletal: Dystonia, muscle spasm, rhabdomyolysis (Aslan 2019)
Hypersensitivity to trientine or any component of the formulation.
Concerns related to adverse effects:
• Copper deficiency: Induced by treatment; may lead to hepatic iron overload and/or sideroblastic anemia; reassess dose (AASLD [Schilsky 2022]).
• Hypersensitivity: Hypersensitivity reactions, characterized by rash, have been reported with trientine tetrahydrochloride (Cuvrior). Hypersensitivity has not been reported with trientine hydrochloride (Clovique and generics, Syprine); however, industrial workers exposed to trientine for prolonged periods have reported asthma, bronchitis, and dermatitis.
• Iron deficiency: May cause iron-deficiency potentially resulting in anemia, especially in menstruating or pregnant females.
• Neurologic worsening: May occur with treatment initiation; less common than with penicillamine (AASLD [Schilsky 2022]).
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, 500 mg
Tablet, Oral, as tetrahydrochloride:
Cuvrior: 300 mg [scored]
May be product dependent
Capsules (Syprine Oral)
250 mg (per each): $255.20
Capsules (Trientine HCl Oral)
250 mg (per each): $229.43 - $242.44
500 mg (per each): $460.00
Tablets (Cuvrior Oral)
300 mg (per each): $240.66
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 250 mg
Oral: Administer at least 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 [Schilsky 2022]; EASL 2012).
Trientine hydrochloride capsules (Clovique and generics, Syprine): 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.
Trientine tetrahydrochloride tablets (Cuvrior): Swallow whole; do not crush, chew, or dissolve tablets. Scored tablet may be divided into 2 equal halves.
Oral: Trientine hydrochloride capsules (Clovique and generics, Syprine): 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 [Schilsky 2022]; 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.
Wilson disease:
Trientine hydrochloride capsules (Clovique and generics, Syprine): Treatment of patients with Wilson disease who are intolerant to penicillamine.
Limitations of use: Not recommended in cystinuria or rheumatoid arthritis; not indicated for biliary cirrhosis.
Trientine tetrahydrochloride tablets (Cuvrior): Treatment of adult patients with stable Wilson disease who are decoppered and tolerant to penicillamine.
Trientine may be confused with TRENtal®, tretinoin
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 [Schilsky 2022]; EASL 2012).
Treatment of Wilson disease should be maintained during pregnancy; dose reduction (25% to 50% of prepregnancy dose) should be considered (AASLD [Schilsky 2022]).
It is not known if trientine is present in breast milk. The manufacturer recommends that caution be exercised when administering trientine to breastfeeding patients.
Should be taken 1 hour before or 2 hours after meals and at least 1 hour apart from any drug, food, or milk.
Periodic 24-hour urinary copper assessment (every 6 to 12 months); serum non-ceruloplasmin bound copper (NCC) at baseline, 3 months after treatment initiation, and approximately every 6 months thereafter; liver biochemistries; CBC; tests of liver synthetic function (eg, INR); urinalysis (AASLD [Schilsky 2022]); fever and skin changes during the first month of therapy.
Treatment efficacy : Adequacy of the initial dose is monitored by the rate of urinary copper excretion; 24-hour urinary copper excretion may exceed 1,000 mcg per 24 hours at treatment initiation and decrease as copper stores are depleted (eg, ~150 to 500 mcg per 24 hours during maintenance therapy) (AASLD [Schilsky 2022]).
Lack of efficacy: Nonadherence versus poor trientine absorption may need to be investigated if urinary copper excretion rises over time (eg >500 mcg per 24 hours) in conjunction with a rise in serum copper and NCC (eg >15 mcg/dL) despite appropriately titrated trientine dosage (AASLD [Schilsky 2022]).
Overtreatment: Overtreatment may need to be investigated if urinary copper excretion is <100 mcg per 24 hours and/or serum copper levels and NCC (eg <5 mcg/dL) are lower than expected (AASLD [Schilsky 2022]).
Trientine is an oral chelating agent structurally dissimilar from penicillamine and other available chelating agents. Induces cupriuresis by chelating with copper to form stable, soluble complexes that are excreted in the urine; also chelates copper in the intestinal tract to decrease copper absorption.
Absorption: Poor (AASLD [Schilsky 2022]); trientine tetrahydrochloride is absorbed faster and to a greater extent than trientine hydrochloride (Weiss 2021).
Metabolism: To acetyltrien (chelating activity significantly less than parent) (AASLD [Schilsky 2022]).
Half-life elimination: Trientine hydrochloride (as Univar [international product]): Mean 23.2 hours (Weiss 2021); Trientine tetrahydrochloride: 13.8 to 16.5 hours.
Time to peak, serum: Trientine hydrochloride (as Univar [international product]): Median: 3 hours (range: 1.25 to 6.02 hours) (Weiss 2021); Trientine tetrahydrochloride: 1.25 to 2 hours.
Excretion: Urine (1% as parent; 8% as metabolite) (AASLD [Schilsky 2022]).
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