Trientine

Class: Heavy Metal Antagonists
Chemical Name: N'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine;dihydrochloride
Molecular Formula: C₆H₂₀Cl₂N₄
CAS Number: 38260-01-4
Brands: Syprine

Medically reviewed by Drugs.com. Last updated on Jan 25, 2021.

• Uses
• Dosage
• Cautions
• Interactions
• Pharmacokinetics
• Patient advice
• Preparations

Introduction

Heavy metal antagonist; selective copper-chelating agent.^{1 3 5 9}

Uses for Trientine

Wilson Disease

Used to promote excretion of copper in patients with Wilson disease (hepatolenticular degeneration) who are intolerant of penicillamine^{1 3 4 5} (designated an orphan drug by FDA for this use).² Manufacturer states that trientine should be used when continued treatment with penicillamine is no longer possible (e.g., because of intolerable or life-threatening adverse effects).¹

American Association for the Study of Liver Diseases (AASLD) recommends a chelating agent (penicillamine or trientine) for initial therapy of symptomatic patients.³ Penicillamine traditionally used as the chelating agent of choice, but is associated with many adverse effects.³ Trientine may be better tolerated and should be considered in patients who cannot take penicillamine.^{3 4 5 10}

Disease manifestations, particularly neurologic symptoms, may worsen during initial therapy.^{3 4 5 8}

Once symptoms and laboratory abnormalities stabilize with initial chelating therapy (typically after 2–6 months, but potentially up to 5 years), patients may continue on a lower dosage of the chelating agent or switch to zinc for maintenance therapy.^{3 4 8}

Because substantial morbidity and mortality can be prevented by treating asymptomatic/presymptomatic patients, AASLD and other experts recommend that such patients also be treated with a chelating agent (generally at a lower dosage than that used in symptomatic patients) or zinc.^{3 4 5}

Treatment is lifelong unless a liver transplant is performed.^{3 4 5 8} Discontinuance of therapy may result in clinical decompensation and/or death.^{3 5 8}

Use in conjunction with low copper diet.^{1 3 5}

Not recommended in the treatment of cystinuria or rheumatoid arthritis due to lack of efficacy in these conditions.¹

Not indicated for treatment of biliary cirrhosis.¹

Trientine Dosage and Administration

General

• Clinical experience is limited; administer under regular medical supervision.¹

• Measure body temperature nightly for the first month of therapy.¹ (See Advice to Patients.)

Administration

Oral Administration

Administer orally on an empty stomach, at least 1 hour before or 2 hours after meals, and at least 1 hour apart from any other drug, food, or milk.¹

Swallow capsules whole with water; do not open or chew.¹ Potential for contact dermatitis with contents of capsule; wash any site of exposure with water.¹

Administer total daily dosage in divided doses 2–4 times daily.¹

Dosage

Dosage of trientine hydrochloride is expressed in terms of the salt.¹

Recommended dosage regimens are based on limited clinical experience; studies have not been conducted evaluating specific doses and/or dosing intervals.^{1 3}

Pediatric Patients

Wilson Disease

Oral

Manufacturer recommends initial dosage of 500–750 mg daily, administered in 2–4 divided doses.¹ A weight-based dosage of 20 mg/kg daily, rounded to the nearest 250 mg and administered in 2–3 divided doses, also has been used.^{3 5}

May increase up to maximum recommended dosage.¹ (See Prescribing Limits under Dosage and Administration.)

Once disease symptoms and laboratory abnormalities stabilize, may continue on a lower dosage for maintenance therapy.^{3 4 5}

Individualize dosage based on urinary copper excretion and serum free copper concentrations in order to maintain negative copper balance.¹ Serum free copper concentrations <10 mcg/dL usually are indicative of adequate maintenance dosage.¹ Increase dosage only if inadequate clinical response or if serum free copper concentrations persistently >20 mcg/dL.¹

Monitor 24-hour urinary copper analysis periodically (i.e., every 6–12 months).¹ Under a low copper diet, 24-hour urinary copper excretion of 0.5–1 mg usually indicates negative copper balance;¹ patients on adequate maintenance treatment should have a 24-hour urinary copper excretion of about 0.2–0.5 mg.^{3 5}

Adults

Wilson Disease

Oral

Manufacturer recommends initial dosage of 750 mg to 1.25 g daily, administered in 2–4 divided doses.¹

May increase up to maximum recommended dosage.¹ (See Prescribing Limits under Dosage and Administration.)

Once disease symptoms and laboratory abnormalities stabilize, may continue on a lower dosage for maintenance therapy.^{3 4 5} Typical maintenance dosages generally are in the range of 750 mg to 1 g daily in 2–3 divided doses.^{3 5}

Individualize dosage based on urinary copper excretion and serum free copper concentrations in order to maintain negative copper balance.¹ Serum free copper concentrations <10 mcg/dL usually are indicative of adequate maintenance dosage.¹ Increase dosage only if inadequate clinical response or if serum free copper concentrations persistently >20 mcg/dL.¹

Monitor 24-hour urinary copper analysis periodically (i.e., every 6–12 months).¹ Under a low copper diet, 24-hour urinary copper excretion of 0.5–1 mg usually indicates negative copper balance;¹ patients on adequate maintenance treatment should have a 24-hour urinary copper excretion of about 0.2–0.5 mg.^{3 5}

Prescribing Limits

Pediatric Patients

Wilson Disease

Oral

1.5 g daily (patients ≤12 years of age).¹

Adults

Wilson Disease

Oral

2 g daily.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

No specific dosage recommendations at this time.¹

Geriatric Patients

No specific dosage recommendations at this time.¹

Pregnant Women

Some experts recommend dosage reduction.³ (See Pregnancy under Cautions.)

Cautions for Trientine

Contraindications

• Hypersensitivity to trientine hydrochloride or any ingredient in the formulation.¹

Warnings/Precautions

Iron Deficiency

Iron deficiency may occur, particularly in children and menstruating women; low copper diet also may contribute.¹

Monitor closely for iron deficiency anemia.¹ May treat iron deficiency with short courses of iron supplementation; however, separate administration of iron and trientine by ≥2 hours.¹ (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity reactions not reported in patients with Wilson disease; however, asthma, bronchitis, and dermatitis reported after prolonged environmental exposure to trientine when used as an epoxy resin hardener.¹

Monitor closely for possible hypersensitivity reactions.¹

Specific Populations

Pregnancy

No adequate data in pregnant women; use during pregnancy only when clearly needed.¹ Teratogenic effects observed in animals.¹

AASLD states that treatment for Wilson disease should be continued during pregnancy because interruption of therapy can result in acute liver failure.^{3 5 10} Limited clinical experience indicates successful pregnancy outcomes when trientine was used during pregnancy.^{3 4} AASLD recommends that dosage be reduced to the minimum necessary (e.g., 25–50% of the prepregnancy dosage), particularly during the third trimester, to promote better wound healing if cesarean section is performed.^{3 5 10} Monitor patient frequently.^{3 5}

Lactation

Not known whether trientine is distributed into milk.¹ Use caution in nursing women.¹

Pediatric Use

Has been used clinically in patients as young as 6 years of age with no reported adverse experiences.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Common Adverse Effects

Iron deficiency.¹

Interactions for Trientine

Specific Drugs

Formal drug interaction studies not conducted to date.⁹

Trientine Pharmacokinetics

Absorption

Bioavailability

Poorly absorbed following oral administration; peak plasma concentrations occur between 0.8–4 hours.⁹

Onset

Increased cupruresis most evident during the first 12 hours following oral administration with highest rate of cupruresis occurring within the first 4 hours.^{6 7}

Food

Food inhibits absorption.^{5 9}

Elimination

Metabolism

Metabolized to 2 major acetyl metabolites, DAT and MAT; MAT also has chelating properties, but is a substantially weaker chelator of copper, iron, and zinc than parent drug.⁹

Elimination Route

Excreted in urine as unchanged drug (1%) and metabolites (8%).^{3 7}

Half-life

1.3–4 hours following single dosing^{6 9} and about 10 hours following steady-state dosing at 1.2 g daily.^{7 9}

Stability

Storage

Oral

Capsules

2–8°C in tightly closed container.¹

Actions

• Selective copper chelating agent that is structurally distinct from penicillamine; chelates copper to form stable complex that is excreted by the kidneys.^{1 3 5 9}

• Removes excess copper in patients with Wilson disease.^{1 3 5 9}

• On a molar basis, appears to be less potent than penicillamine as a cupriuretic agent.¹

• Also chelates other metals including iron and zinc.^{3 5}

Advice to Patients

• Importance of swallowing capsules whole with water, and not chewing or opening.¹

• Because contents of the capsule may cause contact dermatitis, immediately wash any site of skin exposure with water.¹

• Importance of patients measuring their body temperature nightly for the first month of treatment and reporting any symptoms such as fever or skin eruption.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements (e.g., iron, mineral supplements), as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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