Trilawil (Trientine tetrahydrochloride)

What is Trilawil?

Trilawil is a prescription medication containing Trientine tetrahydrochloride, a copper-chelating agent used in the management of Wilson’s disease, a rare genetic disorder characterized by excessive accumulation of copper in the liver, brain, and other tissues. Trilawil helps remove excess copper from the body and prevents its re-accumulation, thereby reducing symptoms and preventing disease progression.

How Trilawil Works?

Trilawil (Trientine tetrahydrochloride) works as a chelating agent by binding free copper ions in the bloodstream and tissues to form a stable complex. These copper–trientine complexes are excreted via the urine, thereby reducing copper levels in the liver and other organs. Additionally, trientine enhances endogenous metallothionein synthesis, a copper-binding protein that reduces copper absorption in the intestine. Overall, this dual action helps maintain safe copper levels in patients with Wilson’s disease.

Who Should Take Trilawil?

Trilawil is indicated for:

• Treatment of Wilson’s disease in patients intolerant to D-penicillamine or when D-penicillamine therapy is contraindicated.
• Maintenance therapy after initial copper reduction to prevent re-accumulation.
• Suitable for both adult and pediatric patients under close medical supervision.

Product Specifications

Dosage and Administration

Standard Dosing: Trientine: 20 mg/kg/day in 2–3 divided doses (max 2 g/day).

Trilawil Capsule:

• Adults (≥13 years): 750 to 1250 mg, orally, in divided doses given 2, 3, or 4 times daily.
  Maximum dose: 2000 mg daily.
• Children (≤12 years): 500 to 750 mg, orally, in divided doses given 2, 3, or 4 times daily.
  Maximum dose: 1500 mg daily to be administered 1 hour before or 2 hours after meals.

Administration Guidelines:

• Take 1 hour before or 2 hours after meals for optimal absorption.
• Avoid taking with iron supplements, zinc, or food, as they reduce absorption.
• Swallow capsules whole with water.
• Maintain consistent dosing times daily.

Monitoring Requirements

Regular monitoring is essential to ensure safe and effective therapy:

• Serum free copper and total copper
• 24-hour urinary copper excretion
• Liver function tests (ALT, AST, bilirubin)
• Complete blood count (CBC)
• Renal function tests

Monitoring frequency should be determined by the treating physician, especially during initiation and dose adjustments.

Safety Information

Common Side Effects

• Most common adverse reactions (>5%) are abdominal pain, change of bowel habits, rash, alopecia, and mood swings.

Serious Warnings

• Potential for Worsening of Clinical Symptoms at Initiation of Therapy: May include neurological deterioration. Adjust dosage or discontinue Trilawil if clinical condition worsens.
• Copper Deficiency: Periodic monitoring is required.
• Iron Deficiency: If iron deficiency develops, a short course of iron supplementation may be given.
• Hypersensitivity Reactions: If rash or other hypersensitivity reaction occurs, consider discontinuing.

Drug Interactions

Avoid concomitant administration with:

• Iron or zinc supplements (take at least 2 hours apart)
• Antacids containing aluminium or magnesium
• Other copper-chelating agents, unless prescribed by a specialist
• Food, as it decreases absorption of trientine

Storage Requirements

• Store below 25°C in a dry, airtight container.
• Protect from moisture and direct light.
• Keep out of reach of children.

Product Pricing and Availability

• Available Pack Sizes: 100 Capsules per bottle
• Pricing Information MRP: ₹18,749 per bottle
• Where to Purchase: Call customer care number: 7337585050

Frequently Asked Questions (FAQ)

FDA Approval and Clinical Evidence

Trientine hydrochloride was first approved by the U.S. FDA as an alternative chelating agent for Wilson’s disease. Clinical studies demonstrate its efficacy in reducing hepatic copper, improving neurological symptoms, and maintaining long-term remission in patients intolerant to D-penicillamine.

Clinical Evidence:

Therapeutic Efficacy and Safety of Trientine Tetrahydrochloride

Trientine tetrahydrochloride is the first drug in its class with an extensive and well-characterized pharmacodynamics, pharmacokinetic, and metabolism profile. Trientine is a selective copper chelator with a dual mechanism of action. As a systemic copper chelator, trientine eliminates absorbed copper from the body by forming a stable complex that is then eliminated through urinary excretion. TETA-4HCl was developed to address room temperature stability and adherence challenges.

The molecular structure of trientine has four amine groups that can bind hydrochloride. The stability challenges associated with its two unbound amine groups to oxidative reactions. These amine groups are sensitive to oxygen, water, temperature, and humidity, which can lead to product degradation over time. Moreover, interactions between these reactive amine groups and excipients may trigger the Maillard reaction, further exacerbating stability issues.

To overcome these stability challenges, the development of TETA-4HCl included the addition of two further hydrochloride groups to the molecule, so that all four amines are bonded to the hydrochloride moiety. This modification effectively neutralized all the reactive amine groups, resulting in a more stable molecule.

The phase I TRIUMPH study conducted in healthy subjects demonstrated that the median time to reach maximum plasma concentration was 2 h for TETA-4HCl provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamics, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics.

Phase III CHELATE Study:

• The CHELATE trial provides robust evidence supporting Trientine tetrahydrochloride the without compromising efficacy in the treatment of Wilson disease. The study enrolled 53 adult subjects (aged 18–75 years) with clinically stable Wilson disease, with a Leipzig score ≥4 at diagnosis
• TETA- 4HCl first-line treatment, post de-coppering, and prior to the development of adverse events secondary to other chelating agent therapy has a conditional boxed warning label because of potential serious adverse reactions and clinical reports of up to 30% of patients experiencing adverse reactions necessitating discontinuation. In contrast, trientine has a better safety profile and is nonimmunogenic.
• Trientine tetrahydrochloride was well tolerated and during treatment, more patients achieved the pre-specified composite endpoint of non-ceruloplasmin-bound copper and 24-hour urinary copper excretion within therapeutic target ranges.

Patient Support and Resources

Important Reminders

• Take Trilawil exactly as prescribed by your healthcare provider
• Do not adjust your dose without medical supervision
• Keep all scheduled appointments for monitoring
• Report any new symptoms or concerns promptly
• Store medication properly and check expiration dates
• Ensure adequate supply and refill prescriptions in advance
• Educate family members and caregivers about your condition and emergency signs