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Trientine

Pronunciation

(TRYE en teen)

Index Terms

  • 2,2,2-tetramine
  • Trien
  • Trientine HCl
  • Trientine Hydrochloride
  • Triethylene Tetramine Dihydrochloride

Dosage Forms

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

Capsule, Oral, as hydrochloride:

Syprine: 250 mg

Brand Names: U.S.

  • Syprine

Pharmacologic Category

  • Chelating Agent

Pharmacology

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 (Roberts 2008)

Metabolism

To acetyltrien (chelating activity significantly less than parent) (Roberts 2008)

Excretion

Urine (1% as parent; 8% as metabolite) (Roberts 2008)

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.

Contraindications

Hypersensitivity to trientine or any component of the formulation.

Dosing: Adult

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 (Roberts 2008). Optimal long-term maintenance dosage should be determined at 6- to 12-month intervals.

Dosing: Geriatric

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

Dosing: Pediatric

Wilson disease: Children and Adolescents: Oral: Initial: 500 to 750 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 in children ≤12 years: 1,500 mg/day. AASLD practice guidelines suggest 20 mg/kg/day rounded off to the nearest 250 mg, given in 2 to 3 divided doses (Roberts 2008). Optimal long-term maintenance dosage should be determined at 6- to 12-month intervals.

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

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

Administration

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.

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.

Storage

Store at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Antacids: May decrease the absorption of Trientine. Management: Separate trientine dosing from other oral drugs (eg, antacids) by at least 1 hour. Monitor for decreased therapeutic effects of trientine if an antacid is initiated/dose increased, or increased effects if an antacid is discontinued/dose decreased. Consider therapy modification

Calcium Salts: May decrease the serum concentration of Trientine. Trientine may decrease the serum concentration of Calcium Salts. Consider therapy modification

Carbonic Anhydrase Inhibitor Diuretics: May decrease the serum concentration of Trientine. Monitor therapy

Iron Salts: Trientine may decrease the serum concentration of Iron Salts. Iron Salts may decrease the serum concentration of Trientine. Management: Trientine manufacturer recommends avoiding concurrent use with oral iron salts due to the risk for impaired GI absorption of both trientine and the iron salt. Short courses of iron may be used; however, separate administration by at least 2 hours. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Magnesium Salts: Trientine may decrease the serum concentration of Magnesium Salts. Magnesium Salts may decrease the serum concentration of Trientine. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Trientine. Management: Trientine manufacturer recommends avoiding concurrent administration with oral minerals due to the risk for impaired GI absorption of both trientine and the mineral. Short courses of iron may be used; however, separate administration by at least 2 hours. Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Trientine. Management: Trientine manufacturer recommends avoiding concurrent administration with oral minerals. The recommendation is that trientine be taken at least one hour before or two hours after meals and at least one hour apart from any drug, food, or milk. Consider therapy modification

Zinc Salts: Trientine may decrease the serum concentration of Zinc Salts. Zinc Salts may decrease the serum concentration of Trientine. Consider therapy modification

Adverse Reactions

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)

Warnings/Precautions

Concerns related to adverse effects:

• Anemia: May cause iron-deficiency anemia; monitor closely, especially women.

• Copper deficiency: Induced by treatment; may lead to hepatic iron overload and/or sideroblastic anemia; reassess dose (Roberts 2008).

• Neurologic worsening: May occur with treatment initiation; less common than with penicillamine (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.

Monitoring Parameters

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

Pregnancy Considerations

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

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of lupus (rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, angina or shortness of breath, or swelling in the arms or legs), difficulty moving, muscle spasm, severe loss of strength and energy, or muscle weakness (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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