General

Pronunciation:
trye-en-teen

Trade Name(s)

• Cuvrior
• Syprine

Ther. Class.

antidotes

Pharm. Class.

chelating agents

Indications

•  Cuvrior: Stable Wilson disease in patients who are decoppered and tolerant to penicillamine.
•  Syprine: Wilson disease in patients who are intolerant to penicillamine.

Action

Forms a complex with absorbed copper, which is then eliminated from the body through the urine. Also binds to copper in the GI tract, reducing its absorption.

Therapeutic Effect(s):

Reduction of copper concentrations in the bloodstream.

Pharmacokinetics

Absorption: Poorly absorbed from GI tract.

Distribution: Unknown.

Metabolism and Excretion: Acetylated into two major active metabolites. Trientine and active metabolites are excreted into urine.

Half-life: 13.8–16.5 hr

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity.

Use Cautiously in:

• Lactation:  Safety not established in breastfeeding;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

Derm: rash, alopecia

GI: abdominal pain, constipation

Hemat: anemia

Neuro: mood swings

Misc: copper deficiency, hypersensitivity reactions, iron deficiency, systemic lupus erythematosus

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

May bind to other medications; avoid concurrent use with  iron supplements,  zinc supplements,  calcium supplements, and  magnesium supplements. If oral iron needs to be administered, separate iron from trientine by ≥2 hr. If administration of oral zinc, calcium, or magnesium supplements unavoidable, administer trientine ≥1 hr before or ≥2 hr after supplement. Administer trientine ≥1 hr apart from any other oral medication.

Route/Dosage

Trientine formulations are not interchangeable on a mg-to-mg basis.

Cuvrior

PO (Adults): Starting dose of trientine depends on dose of penicillamine that patient will be switching from. Discontinue penicillamine before starting trientine.  Previous penicillamine dose 125 mg/day: 300 mg in the morning;  Previous penicillamine dose 250 mg/day: 300 mg twice daily;  Previous penicillamine dose 375 mg/day or 500 mg/day: 600 mg in the morning and 300 mg in the evening;  Previous penicillamine dose 625 mg/day: 600 mg twice daily;  Previous penicillamine dose 750 mg/day: 900 mg in the morning and 600 mg in the evening;  Previous penicillamine dose 875 mg/day: 900 mg twice daily;  Previous penicillamine dose 1000 mg/day: 1200 mg in the morning and 900 mg in the evening;  Previous penicillamine dose 1125 mg/day or 1250 mg/day: 1200 mg twice daily;  Previous penicillamine dose 1375 mg/day: 1500 mg in the morning and 1200 mg in the evening;  Previous penicillamine dose ≥1500 mg/day: 1500 mg twice daily. Adjust total daily dosage based on clinical assessment and laboratory monitoring of copper. Daily dose should not exceed 3000 mg/day.

Syprine

PO (Adults): 750–1250 mg/day given in 2–4 divided doses. Adjust total daily dosage based on clinical assessment and laboratory monitoring of copper. Daily dose should not exceed 2000 mg/day.

Availability (generic available)

Tablets (Cuvrior): 300 mg

Capsules (Syprine): 250 mg

Assessment

• Assess for improvement of symptoms (neurological or hepatic symptoms).
• Monitor for copper deficiency, especially in pregnant patients when appropriate control of levels is required to ensure proper growth and mental development.
• Monitor for iron deficiency, especially in menstruating or pregnant patients, or as a result of the low-copper diet recommendation for Wilson disease.
• Monitor body temperature nightly during first mo of therapy. Report any fevers.
• Monitor for hypersensitivity reactions (rash, dermatitis).  If hypersensitivity reactions occur,  assess clinically and consider discontinuing trientine.

Lab Test Considerations:

• Monitor serum nonceruloplasmin copper levels before starting therapy, 3 mo after starting therapy, and every 6 mo thereafter. May be monitored periodically (every 6–12 mo) with measurement of 24-hr urinary copper excretion.
• Monitor iron levels.
• Monitor liver function tests (ALT, AST, bilirubin, alkaline phosphatase).
• Monitor renal function (BUN, serum creatinine, urinalysis). Observe for proteinuria.
• Monitor CBC with differential. Monitor for anemia and leukopenia.

Implementation

• Confirm penicillamine has been discontinued before starting trientine.
• PO Administer on an empty stomach, >1 hr before or 2 hr after meals, and >1 hr apart from any other drug, food, or milk. Administer >2 hr before or after iron supplements. Administer >1 hr before or 2 hr after other mineral supplements (zinc, calcium, magnesium). Any skin exposed to the contents of a capsule should be promptly washed with water.  DNC: Swallow tablets whole. Do not crush, chew, or dissolve tablets.   For Cuvrior,  do not remove tablets from blister pack until just before dosing, and do not store for future use once blister has been opened. Scored tablets may be divided into two equal halves if patient has difficulty swallowing. Avoid use if patients are unable to swallow tablets.

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Advise to take as directed, and adhere to dietary restrictions. Take a missed dose as soon as remembered. If it is close to the time for next dose, skip the missed dose and go back to normal time. Do not take two doses at the same time or extra doses.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
• Advise patient to adhere to routine laboratory testing.
• Advise patient of signs and symptoms of neurological deterioration, jaundice, or worsening fatigue and to notify health care professional if any occur.
• Advise patient to notify health care professional immediately if signs and symptoms of copper or iron deficiency occur, as well as hypersensitivity reactions.
• Advise patient to restrict high-copper foods (shellfish, whole grains, beans, nuts).
• Educate the patient on the potential of hair loss.
• Rep:  Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Monitor copper levels and use minimum effective dosage throughout pregnancy.

Evaluation/Desired Outcomes

Reduction of copper concentrations in the bloodstream.