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
Introduction
Heavy metal antagonist; selective copper-chelating agent.
Uses for Trientine
Wilson Disease
Used to promote excretion of copper in patients with Wilson disease (hepatolenticular degeneration) who are intolerant of penicillamine (designated an orphan drug by FDA for this use). 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).
American Association for the Study of Liver Diseases (AASLD) recommends a chelating agent (penicillamine or trientine) for initial therapy of symptomatic patients. Penicillamine traditionally used as the chelating agent of choice, but is associated with many adverse effects. Trientine may be better tolerated and should be considered in patients who cannot take penicillamine.
Disease manifestations, particularly neurologic symptoms, may worsen during initial therapy.
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.
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.
Treatment is lifelong unless a liver transplant is performed. Discontinuance of therapy may result in clinical decompensation and/or death.
Use in conjunction with low copper diet.
Not recommended in the treatment of cystinuria or rheumatoid arthritis due to lack of efficacy in these conditions.
Not indicated for treatment of biliary cirrhosis.
Trientine Dosage and Administration
General
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Clinical experience is limited; administer under regular medical supervision.
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Measure body temperature nightly for the first month of therapy. (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.
Swallow capsules whole with water; do not open or chew. Potential for contact dermatitis with contents of capsule; wash any site of exposure with water.
Administer total daily dosage in divided doses 2–4 times daily.
Dosage
Dosage of trientine hydrochloride is expressed in terms of the salt.
Recommended dosage regimens are based on limited clinical experience; studies have not been conducted evaluating specific doses and/or dosing intervals.
Pediatric Patients
Wilson Disease
Oral
Manufacturer recommends initial dosage of 500–750 mg daily, administered in 2–4 divided doses. 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.
May increase up to maximum recommended dosage. (See Prescribing Limits under Dosage and Administration.)
Once disease symptoms and laboratory abnormalities stabilize, may continue on a lower dosage for maintenance therapy.
Individualize dosage based on urinary copper excretion and serum free copper concentrations in order to maintain negative copper balance. Serum free copper concentrations <10 mcg/dL usually are indicative of adequate maintenance dosage. Increase dosage only if inadequate clinical response or if serum free copper concentrations persistently >20 mcg/dL.
Monitor 24-hour urinary copper analysis periodically (i.e., every 6–12 months). Under a low copper diet, 24-hour urinary copper excretion of 0.5–1 mg usually indicates negative copper balance; patients on adequate maintenance treatment should have a 24-hour urinary copper excretion of about 0.2–0.5 mg.
Adults
Wilson Disease
Oral
Manufacturer recommends initial dosage of 750 mg to 1.25 g daily, administered in 2–4 divided doses.
May increase up to maximum recommended dosage. (See Prescribing Limits under Dosage and Administration.)
Once disease symptoms and laboratory abnormalities stabilize, may continue on a lower dosage for maintenance therapy. Typical maintenance dosages generally are in the range of 750 mg to 1 g daily in 2–3 divided doses.
Individualize dosage based on urinary copper excretion and serum free copper concentrations in order to maintain negative copper balance. Serum free copper concentrations <10 mcg/dL usually are indicative of adequate maintenance dosage. Increase dosage only if inadequate clinical response or if serum free copper concentrations persistently >20 mcg/dL.
Monitor 24-hour urinary copper analysis periodically (i.e., every 6–12 months). Under a low copper diet, 24-hour urinary copper excretion of 0.5–1 mg usually indicates negative copper balance; patients on adequate maintenance treatment should have a 24-hour urinary copper excretion of about 0.2–0.5 mg.
Prescribing Limits
Pediatric Patients
Wilson Disease
Oral
1.5 g daily (patients ≤12 years of age).
Adults
Wilson Disease
Oral
2 g daily.
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.
Renal Impairment
No specific dosage recommendations at this time.
Geriatric Patients
No specific dosage recommendations at this time.
Pregnant Women
Some experts recommend dosage reduction. (See Pregnancy under Cautions.)
Cautions for Trientine
Contraindications
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Hypersensitivity to trientine hydrochloride or any ingredient in the formulation.
Warnings/Precautions
Iron Deficiency
Iron deficiency may occur, particularly in children and menstruating women; low copper diet also may contribute.
Monitor closely for iron deficiency anemia. May treat iron deficiency with short courses of iron supplementation; however, separate administration of iron and trientine by ≥2 hours. (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.
Monitor closely for possible hypersensitivity reactions.
Specific Populations
Pregnancy
No adequate data in pregnant women; use during pregnancy only when clearly needed. Teratogenic effects observed in animals.
AASLD states that treatment for Wilson disease should be continued during pregnancy because interruption of therapy can result in acute liver failure. Limited clinical experience indicates successful pregnancy outcomes when trientine was used during pregnancy. 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. Monitor patient frequently.
Lactation
Not known whether trientine is distributed into milk. Use caution in nursing women.
Pediatric Use
Has been used clinically in patients as young as 6 years of age with no reported adverse experiences.
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Common Adverse Effects
Iron deficiency.
Interactions for Trientine
Specific Drugs
Formal drug interaction studies not conducted to date.
Drug |
Interaction |
Comments |
---|---|---|
Mineral supplements (e.g., iron) |
May inhibit absorption of trientine Complex with iron potentially toxic |
Avoid concomitant use If iron supplementation is necessary, separate administration by ≥2 hours |
Trientine Pharmacokinetics
Absorption
Bioavailability
Poorly absorbed following oral administration; peak plasma concentrations occur between 0.8–4 hours.
Onset
Increased cupruresis most evident during the first 12 hours following oral administration with highest rate of cupruresis occurring within the first 4 hours.
Food
Food inhibits absorption.
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.
Elimination Route
Excreted in urine as unchanged drug (1%) and metabolites (8%).
Half-life
1.3–4 hours following single dosing and about 10 hours following steady-state dosing at 1.2 g daily.
Stability
Storage
Oral
Capsules
2–8°C in tightly closed container.
Actions
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Selective copper chelating agent that is structurally distinct from penicillamine; chelates copper to form stable complex that is excreted by the kidneys.
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Removes excess copper in patients with Wilson disease.
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On a molar basis, appears to be less potent than penicillamine as a cupriuretic agent.
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Also chelates other metals including iron and zinc.
Advice to Patients
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Importance of swallowing capsules whole with water, and not chewing or opening.
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Because contents of the capsule may cause contact dermatitis, immediately wash any site of skin exposure with water.
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Importance of patients measuring their body temperature nightly for the first month of treatment and reporting any symptoms such as fever or skin eruption.
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Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
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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.
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Importance of informing patients of other important precautionary information. (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
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Capsules |
250 mg* |
Syprine |
Valeant |
Trientine Hydrochloride Capsules |
AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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