Copper Toxicity & Liver Health: A Guide to Syprine’s Role in Gastroenterology  

Imagine copper, a seemingly ordinary metal, present in our daily lives and even within our bodies. It is, in fact, an essential trace element, a tiny but mighty component crucial for numerous biological processes, from energy production to nerve function. Our bodies need just the right amount – typically around 1.5 milligrams per day, easily obtained from foods like shellfish, chocolate, and nuts. However, like a delicate balance, when this essential element is present in excess, it transforms from a vital nutrient into a silent threat, particularly to our liver.¹

Understanding Copper Toxicity and Its Impact on Liver Function

The liver, our body's primary metabolic hub, plays a central role in regulating copper levels. It absorbs copper from our diet, incorporates it into vital proteins, and excretes any excess through bile. However, when this intricate system falters, copper begins to accumulate, leading to significant health challenges.  

Copper overload can manifest in different ways. One scenario involves acute copper toxicity, which typically occurs from ingesting large, toxic amounts, often accidentally in children (for example, from swallowing coins) or in intentional overdoses. ¹ Initial symptoms can be immediate and severe, including a metallic taste and intense gastrointestinal distress due to irritation of the stomach and small bowel. In severe cases, this can rapidly escalate to cardiovascular collapse, coma, and even death within hours. ¹   

Liver injury usually follows within 24 to 72 hours, marked by elevated liver enzymes (serum aminotransferases), minimal changes in alkaline phosphatase, and a swift progression to liver failure, jaundice, shock, renal failure, and severe hemolytic anemia, a pattern resembling acute hepatic necrosis.¹

The most common and severe form of chronic copper overload is Wilson disease. This is an inherited genetic disorder caused by a mutation in the ATP7B gene, which is responsible for producing a crucial enzyme in the liver that transports and excretes copper. When this gene is faulty, the body cannot properly eliminate excess copper. As a result, copper begins to accumulate, primarily in the liver. While less common, chronic liver injury can also arise from prolonged, excessive dietary copper intake or environmental exposure, such as from copper tubing used in hemodialysis.¹

Signs and Symptoms of Excess Copper Accumulation¹

Acute Copper Overdose (e.g., from ingestion of 1–10g):

         - Metallic taste

         - Gastrointestinal distress (due to gastric or small bowel erosions)

         - Cardiovascular collapse

         - Markedly elevated serum aminotransferases (AST/ALT)

         - Minimal elevation in alkaline phosphatase

         - Hepatic failure

         - Increased prothrombin time

         - Jaundice

         - Acute hepatic necrosis

         - Other associated complications:

         - Renal failure

         - Rhabdomyolysis

         - Severe hemolytic anemia

         - Increased total bilirubin (partly from hemolysis)

Chronic Copper Overload (e.g., from long-term ingestion or exposure):

         - Chronic liver injury

                 - Mimics Wilson disease

                 - May include signs of advanced liver disease

         - Neurological syndromes

         - Hemolytic anemia

         - Possible involvement of brain and kidney over time

Diagnosis and Clinical Markers in Copper Overload 

Diagnosis of copper overload relies on clinical findings supported by specific laboratory and biopsy markers, as real-time testing is often impractical. Whole-blood copper concentration is the preferred marker, as copper rapidly shifts from serum to red blood cells. Normal levels range from 70 to 140 μg/dl, and elevated levels correlate with the severity of poisoning. Free serum copper, though measurable (normal range 4–7 μg/dl), is less reliable in acute settings. In cases of copper poisoning, 24-hour urinary copper excretion typically rises to 5–25 μg, exceeding normal limits. For chronic overload, liver biopsy is crucial, with normal hepatic copper concentrations ranging from 15 to 55 μg/g of dry liver tissue. Obtaining a complete liver core helps reduce sampling variability. Ceruloplasmin, the primary copper-carrying protein in plasma, normally ranges from 20 to 35 mg/dl. While its levels may rise in acute copper poisoning due to increased liver synthesis, this elevation does not provide prognostic information.²

What Is Syprine and How Does It Work? 

Syprine is a brand name for trientine dihydrochloride, a medication used to treat Wilson’s disease. It works as a chelating agent, meaning it binds to excess copper in the body to form a complex that can be safely removed. Once absorbed, trientine and its metabolites bind to free copper and help eliminate it through the urine. However, the drug is not well absorbed when taken with food, so it should be taken on an empty stomach for best effect.³

Syprine’s Mechanism of Action in Chelating Copper

Trientine works through a dual mechanism of action to treat Wilson’s disease by targeting excess copper in the body. First, as a systemic copper chelator, trientine binds to absorbed copper in the bloodstream to form a stable complex that is then eliminated through urinary excretion. This is especially important in newly diagnosed patients where large amounts of copper need to be cleared from organs and tissues. ⁴

Second, trientine acts within the intestinal tract to inhibit copper absorption, thereby reducing copper transport through the portal vein and its uptake by the liver. This intestinal effect helps prevent further accumulation of copper. ⁴

Clinical Benefits of Syprine in Liver-Related Disorders 

Trientine has shown significant clinical benefits in patients with liver-related manifestations. In a prospective pilot study, patients maintained on once-daily weight-based trientine therapy showed stable liver function, with minimal changes in aminotransferase levels and no significant changes in markers of hepatic fibrosis, such as AST-to-platelet ratio. Importantly, INR, albumin, and bilirubin levels remained within normal ranges, suggesting preserved hepatic synthetic function.⁵

Syprine Dosage Guidelines and Administration Protocol⁶ 

The recommended initial daily dose is:

• Pediatric patients (age 12 or under): 500–750 mg/day
• Adults: 750–1250 mg/day

These doses should be divided into two, three, or four doses per day. The dose may be increased if clinical response is inadequate or if free serum copper remains above 20 mcg/dL. The maximum daily dose is 1500 mg for pediatric patients and 2000 mg for adults.

Long-term maintenance dosing should be reassessed every 6 to 12 months based on clinical status and lab monitoring.

For optimal absorption and efficacy, Syprine should be taken on an empty stomach, either at least one hour before meals or two hours after meals, and at least one hour apart from any other food, drug, or milk. Capsules must be swallowed whole with water and should not be opened or chewed.

Syprine vs. Other Copper Chelators 

Unlike other chelators, trientine significantly reduces intestinal uptake of copper isotopes like 64Cu by at least 50%. Together, its systemic and local actions allow trientine to lower free serum copper levels and help maintain long-term copper balance in patients with Wilson’s disease.⁴

Accessing Syprine via the Named Patient Program in India

Syprine is not marketed in India but can be imported legally under the Named Patient Import Program:

1. Treating gastroenterologist registers patient under the program.
2. Valid prescription, diagnosis confirmation, and patient consent obtained.
3. Regulatory clearances, sourcing, and customs.
4. Medication delivered to patient.

Rx4U partners with these logistics experts to streamline Syprine access, ensuring compliance and minimizing turnaround times.

Safety Tips and Considerations for Long-Term Use⁶ 

Syprine capsules should be swallowed whole with water and must not be opened or chewed, as exposure to capsule contents may cause contact dermatitis. Any accidental skin contact should be washed off with water promptly.

During the first month of therapy, patients should check their temperature daily and immediately report symptoms such as fever or skin rashes, as these could indicate a reaction to the medication. While hypersensitivity reactions have not been reported in patients treated with trientine for Wilson’s disease, similar symptoms (including asthma, bronchitis, and dermatitis) have occurred in individuals with prolonged environmental exposure to the compound. Therefore, patients should be observed closely for any signs of hypersensitivity.

Because of the risk of iron deficiency anemia, especially in women, regular monitoring of iron levels is recommended during treatment. Patients should remain under ongoing medical supervision throughout the course of therapy to ensure safe and effective use.

Storage instructions include keeping Syprine at 2° to 8°C (36° to 46°F) and ensuring the container is tightly closed at all times.

FAQs About Syprine Use in Gastroenterology 

Q: Is pediatric use safe?
A: It has been used clinically in pediatric patients as young as 6 years with

no reported adverse experiences.⁶

Q: How does Syprine affect pregnancy?
A: Data are scarce. Use only if benefits outweigh risks; close monitoring is imperative. ⁶

Q: How to get access to Syprine in India?

A: Rx4U navigates the Named Patient Program’s regulatory pathway, coordinating with trusted suppliers to ensure timely, legal importation of Syprine for your patients. Contact Rx4U today to unlock life-saving copper chelation therapy.

Note:

The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.

Disclaimer:

Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import.

References:

1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Copper. [Updated 2017 Oct 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548090/
2. Rahimzadeh MR, Rahimzadeh MR, Kazemi S, Moghadamnia AA. Copper poisoning with emphasis on its clinical manifestations and treatment of intoxication. Biomed Res Int. 2024;2024:6001014. doi:10.1155/2024/6001014
3. Trientine dihydrochloride for Wilson's disease. Aust Prescr. 2021;44(3):111. doi:10.18773/austprescr.2021.022
4. Kamlin COF, M Jenkins T, L Heise J, S Amin N. Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review. Drugs. 2024;84(12):1509-1518. doi:10.1007/s40265-024-02099-0
5. Ala A, Aliu E, Schilsky ML. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease. Dig Dis Sci. 2015;60(5):1433-1439. doi:10.1007/s10620-014-3495-6

 Syprine (trientine tetrahydrochloride) prescribing information. https://pi.bauschhealth.com/globalassets/BHC/PI/Syprine-PI.pdf