Usage
- Trientine Hydrochloride is primarily prescribed for the treatment of Wilson’s disease, a genetic disorder characterized by excessive copper accumulation in the body, particularly in the liver, brain, and eyes. It is used in patients who are intolerant to D-penicillamine, the first-line treatment for Wilson’s disease.
- Pharmacological Classification: Chelating agent.
- Mechanism of Action: Trientine works by binding to copper ions, forming a stable complex that can be excreted in the urine. This process reduces the amount of copper in the body, preventing further damage to organs.
Alternate Names
- Trientine Dihydrochloride
- Brand Names: Syprine, Cuvrior, Trientine Waymade, Cufence (various brands exist depending upon the region and manufacturer)
How It Works
- Pharmacodynamics: Trientine’s primary effect is to reduce free copper levels in the body. This prevents the progression of Wilson’s disease and can even reverse some of the damage caused by copper toxicity.
- Pharmacokinetics: Trientine is absorbed orally, but its bioavailability is reduced when taken with food or other medications containing polyvalent cations (e.g., iron, zinc, magnesium). It is minimally metabolized and primarily excreted in the urine as copper-trientine complexes.
- Mode of Action: Trientine acts as a copper chelator, binding to copper ions through its sulfhydryl groups. This chelation prevents copper from participating in harmful reactions and facilitates its removal.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Initial: 750-1250 mg/day orally, divided into 2-4 doses.
- Maximum: 2000 mg/day.
- Maintenance dose is adjusted based on clinical response and serum free copper levels (target usually below 20 mcg/dL or 3.1 µmol/L).
Children (5-17 years):
- Initial: 20 mg/kg/day or 500-750 mg/day, divided into 2-3 doses. Round the dose to the nearest available capsule strength (usually 250mg).
- Maximum for children ≤12 years: 1500 mg/day.
- Dosage adjustments are made as needed based on clinical response and free serum copper levels.
Special Cases:
- Elderly Patients: Start at the lower end of the adult dosage range.
- Patients with Renal Impairment: No specific dosage adjustment is routinely recommended, but caution is advised, and monitoring is crucial.
- Patients with Hepatic Dysfunction: Close monitoring is required due to potential toxicity or lack of effectiveness.
- Patients with Comorbid Conditions: Consider individual patient factors when adjusting dosage.
Clinical Use Cases
Trientine’s use is specific to Wilson’s disease management. It is not indicated for use in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments are necessary based on individual patient response to therapy, serum free copper levels, and renal or hepatic function.
Side Effects
Common Side Effects
- Skin rash
- Iron deficiency anemia
- Gastric irritation (e.g., heartburn, stomach pain)
Rare but Serious Side Effects
- Leukopenia
- Thrombocytopenia
- Systemic lupus erythematosus-like syndrome
- Hepatotoxicity
Long-Term Effects
Long-term use can lead to iron deficiency anemia, which requires monitoring and supplementation.
Adverse Drug Reactions (ADR)
Adverse reactions necessitate dose adjustments or discontinuation of therapy depending upon severity.
Contraindications
- Hypersensitivity to trientine.
Drug Interactions
- Iron supplements, antacids, and other medications containing polyvalent cations can reduce trientine absorption. Administer trientine at least 1 hour before or 2 hours after these medications.
Pregnancy and Breastfeeding
- While not explicitly contraindicated, the safety of trientine during pregnancy has not been definitively established. Its use should be carefully evaluated based on the potential benefits and risks to both the mother and the fetus.
- The excretion of trientine in breast milk is unknown. Caution is advised when administering to breastfeeding mothers.
Drug Profile Summary
- Mechanism of Action: Copper chelator.
- Side Effects: Skin rash, iron deficiency anemia, gastrointestinal issues, rarely blood cell deficiencies or lupus-like syndrome.
- Contraindications: Hypersensitivity.
- Drug Interactions: Polyvalent cations (e.g., iron, zinc, magnesium, antacids).
- Pregnancy & Breastfeeding: Limited data; caution advised.
- Dosage: Adults: 750-1250 mg/day initially; Children: 20 mg/kg/day initially. Adjust based on response and copper levels.
- Monitoring Parameters: Serum free copper levels, complete blood count, liver function tests, urine copper levels.
Popular Combinations
Trientine is typically used as monotherapy for Wilson’s disease.
Precautions
- General Precautions: Monitor for hematological and hepatic side effects.
- Specific Populations: Close monitoring during pregnancy and breastfeeding; initiate therapy with lower doses in the elderly. Monitor for iron deficiency.
- Lifestyle Considerations: Administer on an empty stomach, separate from other medications and food by at least one hour.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trientine Hydrochloride?
A: Adults: 750-1250 mg/day initially, up to a maximum of 2000 mg/day. Children (5-17 years): 20 mg/kg/day or 500-750 mg/day initially, up to 1500 mg/day for those ≤ 12 years old. Doses are divided into 2-4 administrations per day.
Q2: How is Trientine Hydrochloride administered?
A: Orally, on an empty stomach, at least 1 hour before or 2 hours after meals, and at least 1 hour apart from other medications, food, or milk.
Q3: What is the mechanism of action of Trientine Hydrochloride?
A: It chelates copper, forming a stable complex that is excreted in the urine, reducing copper levels in the body.
Q4: What are the common side effects of Trientine Hydrochloride?
A: Skin rash, iron deficiency anemia, and gastrointestinal issues like heartburn and stomach pain are common.
Q5: What are the serious side effects of Trientine Hydrochloride?
A: Rare but serious side effects include bone marrow suppression (leukopenia, thrombocytopenia) and lupus-like syndrome.
Q6: What are the contraindications to Trientine Hydrochloride use?
A: Known hypersensitivity to trientine is a contraindication.
Q7: What are the key drug interactions with Trientine Hydrochloride?
A: Medications containing polyvalent cations (e.g., iron, zinc, antacids) can interfere with absorption; administer separately.
Q8: Can Trientine Hydrochloride be used during pregnancy and breastfeeding?
A: Data are limited; use with caution and only if the potential benefits outweigh the risks. Discuss risks and benefits with patients.
Q9: How often should monitoring be done while on Trientine?
A: Regular monitoring of serum free copper, blood counts, and liver function is necessary to assess treatment efficacy and detect potential adverse effects. The frequency is determined by the patient’s clinical status.
Q10: What is the role of monitoring serum free copper levels in patients treated with Trientine?
A: Monitoring serum free copper levels is essential for adjusting trientine dosage and assessing the treatment’s effectiveness in managing Wilson’s disease.
