Your activity: 6 p.v.

Trientine: Drug information

Trientine: Drug information
(For additional information see "Trientine: Patient drug information" and see "Trientine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Clovique [DSC];
  • Syprine
Brand Names: Canada
  • MAR-Trientine;
  • Waymade-Trientine
Pharmacologic Category
  • Chelating Agent
Dosing: Adult
Wilson disease

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.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Pediatric

(For additional information see "Trientine: Pediatric drug information")

Wilson disease

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

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing. Use with caution; initiate at lower end of the dosing range.

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Generic: 250 mg

Product Availability

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.

Administration: Adult

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).

Administration: Pediatric

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.

Use: Labeled Indications

Wilson disease: 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.

Medication Safety Issues
Sound-alike/look-alike issues:

Trientine may be confused with TRENtal®, tretinoin

Adverse Reactions

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)

Contraindications

Hypersensitivity to trientine or any component of the formulation.

Warnings/Precautions

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.

Metabolism/Transport Effects

None known.

Drug Interactions

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.

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 Interactions

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).

Pregnancy Considerations

Treatment of Wilson disease should be maintained during pregnancy; dose reduction (25% to 50% of prepregnancy dose) should be considered (AASLD [Roberts 2008]).

Breastfeeding Considerations

It is not known if trientine is present in breast milk. The manufacturer recommends that caution be exercised when administering trientine to breastfeeding patients.

Dietary Considerations

Should be taken 1 hour before or 2 hours after meals and at least 1 hour apart from any drug, food, or milk.

Monitoring Parameters

Periodic 24-hour urinary copper assessment (every 6 to 12 months); serum non-ceruloplasmin bound copper; LFTs; CBC; INR; urinalysis (AASLD [Roberts 2008]); fever and skin changes during the first month of therapy.

Reference Range

Urinary copper excretion: 200 to 500 mcg (3 to 8 micromoles) per day (AASLD [Roberts 2008]).

Mechanism of Action

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

Pharmacokinetics

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]).

Pricing: US

Capsules (Syprine Oral)

250 mg (per each): $255.20

Capsules (Trientine HCl Oral)

250 mg (per each): $229.43 - $242.44

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.

Brand Names: International
  • Metacu (TW);
  • Metalite (JP, TW);
  • Syprine (KR, SG)


For country code abbreviations (show table)
  1. Clovique (trientine hydrochloride) [prescribing information]. Warrendale, PA: Kadmon Pharmaceuticals; December 2018.
  2. Condamine L, Hermine O, Alvin P, Levine M, Rey C, Courtecuisse V. Acquired sideroblastic anaemia during treatment of Wilson's disease with triethylene tetramine dihydrochloride. Br J Haematol. 1993;83(1):166-168. [PubMed 8435326]
  3. Dahlman T, Hartvig P, Löfholm M, Nordlinder H, Lööf L, Westermark K. Long-term treatment of Wilson's disease with triethylene tetramine dihydrochloride (trientine). QJM. 1995;88(9):609-616. [PubMed 7583074]
  4. European Association for Study of Liver. EASL clinical practice guidelines: Wilson's disease. J Hepatol. 2012;56(3):671-685. doi:10.1016/j.jhep.2011.11.007 [PubMed 22340672]10.1016/j.jhep.2011.11.007
  5. Kodama H, Murata Y, Iitsuka T, et al, “Metabolism of Administrated Triethylene Tetramine Dihydrochloride In Humans,” Life Sci, 1997, 61(9):899-907. [PubMed 9284083]
  6. Perry AR, Pagliuca A, Fitzsimons EJ, Mufti GJ, Williams R. Acquired sideroblastic anaemia induced by a copper-chelating agent. Int J Hematol. 1996;64(1):69-72. [PubMed 8757970]
  7. Roberts EA, Schilsky ML; American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008;47(6):2089-2111. [PubMed 18506894]
  8. Shiono Y, Hayashi H, Wakusawa S, Yano M. Ultrastructural identification of iron and copper accumulation in the liver of a male patient with Wilson disease. Med Electron Microsc. 2001;34(1):54-60. [PubMed 11479773]
  9. Socha P, Janczyk W, Dhawan A, et al. Wilson's Disease in Children: A Position Paper by the Hepatology Committee of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018;66(2):334-344. doi: 10.1097/MPG.0000000000001787. [PubMed 29341979]
  10. Syprine (trientine hydrochloride) [prescribing information]. Bridgewater, NJ: Bausch Health US, LLC; September 2020.
  11. Trientine hydrochloride capsules [prescribing information]. Princeton, NJ: Dr. Reddy's Laboratories; July 2019.
  12. Walshe JM, “Treatment of Wilson's Disease With Trientine (Triethylene Tetramine) Dihydrochloride,” Lancet, 1982, 1(8273):643-7. [PubMed 6121964]
Topic 10019 Version 207.0