Trientine (Syprine) is a chelating agent that forms soluble complexes with copper, iron, and zinc resulting in its excretion via urine. It is used in the treatment of patients with Wilson's disease, especially those who are intolerant to penicillamine.

Trientine Uses:

• Wilson disease:

  • It is indicated for the treatment of patients with Wilson disease who are intolerant to penicillamine.
  • Limitations of use: It is not recommended if the patient has concomitant rheumatoid arthritis and cystinuria. It is also not indicated for the treatment of biliary cirrhosis.

Trientine (Syprine) Dose in Adults

Trientine (Syprine) Dose in the treatment of Wilson disease:

• Initial: 750 to 1,250 mg/day orally in two to four divided doses.
• The dose may be increased if the clinical response is not adequate or the concentration of free serum copper persistently exceeds 20 mcg/dL;
• The maximum daily 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.
• The maintenance dosage should be determined at 6- to 12-month intervals for optimum control.

Trientine (Syprine) Dose in Childrens

Trientine (Syprine) Dose in the treatment of Wilson disease:

• Children and Adolescents:

  • Initial: 20 mg/kg/day orally in two or three divided doses (round the dose to the nearest 250 mg).
  • The maximum initial dose: 1,000 mg/day given orally in divided doses;
  • The dose should be titrated based on the treatment response and free serum copper (non-ceruloplasmin bound copper) concentrations and/or 24-hour urinary copper excretion;
  • The usual maintenance dose is 900 to 1,500 mg/day in two or three divided doses.

  • The maximum daily dose:

    • Children:
      • 1,500 mg/day.
    • Adolescents:
      • 2,000 mg/day

Pregnancy Risk Category: C

• It has not yet been tested in human or animal pregnancies.
• Patients who are already receiving treatment should continue to take the drug.
• However, the dosage should be decreased to 25% - 50% of what was used for pregnancies.

Use during breastfeeding:

• It is unknown if the drug is excreted into breastmilk. It is recommended that breastfeeding mothers avoid using the drug.

Dose in Kidney Disease:

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

Dose in Liver disease:

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

Side effects of Trientine (Syprine):

• Central Nervous System:

  • Dystonia
  • Myasthenia Gravis
  • Neurological Deterioration.

• Endocrine & Metabolic:

  • Iron Deficiency

• Gastrointestinal:

  • Gastritis.

• Hypersensitivity:

  • Fixed Drug Eruption.

• Neuromuscular & Skeletal:

  • Muscle Spasm
  • Systemic Lupus Erythematosus

Contraindications to Trientine (Syprine):

Allergy to trientine and any component of this formulation

Warnings and precautions

• Anemia:

  • Because it is a chelating agent, it can cause iron-deficiency andemia. It is important to monitor patients, particularly women with iron deficiency.

• Copper deficiency:

  • It can cause a copper deficiency and possibly sideroblastic and hepatic iron overload. It is important to reevaluate the dose.

• Neurologic decline:

  • Sometimes, patients may experience a worsening in their neurological symptoms after treatment is initiated. 
  • Penicillamine is less likely to cause neurologic worsening.

Trientine: Drug Interaction

Monitoring parameters:

• Monitor 24-hour urinary copper periodically (assess levels every 6 to 12 months);
• Serum-free copper;
• Liver function tests;
• Complete blood count;
• INR;
• Urinalysis;
• Fever and skin changes during the first month of treatment.

How to administer Trientine (Syprine)?

• It is best administered on an empty stomach and at least one hour apart from any food, drug, or milk.
• It should be taken orally one hour before or two hours after meals.
• The capsule should not be opened, chewed, or broken. It should be swallowed whole with water.
• If the skin is exposed to the drug, it should be washed immediately with water. 

Mechanism of action of Trientine (Syprine):

• It is an oral copper chelating agent that causes the body to excrete copper via urine. 
• It has a unique structure that is different from other chelating drugs. 
• It forms soluble complexes of copper with iron and zinc, which are excreted via the kidneys.

Absorption:

• It is not well absorbed.

Metabolism:

• It is metabolized to acetyltrien. The chelating activity of the metabolite is significantly less than the parent compound.

Excretion:

• It is excreted in the urine (1% as a parent drug and 8% as metabolite).

International Brand Names of Trientine:

• Syprine
• Cuprior

Trientine Brand Names in Pakistan:

No Brands Available in Pakistan.