Syprine® (trientine hydrochloride) is a chelating agent. Chelating agents are used to remove heavy metals (eg, lead, mercury, copper) from the blood. Syprine, a brand name of trientine, is manufactured by Bausch Health and was approved by the US Food and Drug Administration on November 8, 1985.1 Trientine hydrochloride is N,N’-bis(2-aminoethyl)-1,2-ethanediamine dihydrochloride.2 Syprine is used to treat patients with Wilson disease who are unable to take the drug penicillamine. An excessive amount of copper is stored by the body in Wilson disease. Syprine, unlike penicillamine, is not recommended for patients with cystinuria, rheumatoid arthritis, or biliary cirrhosis because it is not an effective treatment under these conditions.3 

Syprine is available as oral capsules, each containing a 250-mg dose.4 The recommended dose of Syprine is 500 to 750 mg/day for children and 750 to 1250 mg/day for adults. The medication is given in divided doses 2, 3, or 4 times per day. For adults, the dose can be increased to a daily maximum of 2000 mg; for children, it can be increased to a daily maximum of 1500 mg. The daily dose of Syprine should be increased only when the clinical response is insufficient or the quantity of free serum copper is consistently higher than 20 µg/dL.2 Syprine must be taken on an empty stomach at least 1 hour before a meal or 2 hours after a meal, and at least 1 hour before or after any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed.3 

Mechanism of Action

Trientine hydrochloride is a chelating agent that helps rid the body of extra copper.​​ Wilson disease is a metabolic abnormality with autosomal recessive inheritance. An inability of the liver to eliminate free copper into the bile may be the cause of the accumulation of excess copper. When the capacity of the hepatocytes to store excess copper is reached, copper is released into the blood and taken up in extrahepatic locations. A low-copper diet and chelating drugs, which bind copper and help to eliminate it from the body, are used to treat this condition.5 

Read more about Wilson disease therapies

Efficacy in Trials and Trial Results

Patients who had been using penicillamine for at least a year participated in separate trials evaluating the renal clearance of trientine hydrochloride and penicillamine. The 6-hour rates of copper excretion were calculated with the patients off therapy and again after a single dose of either 1.2 g of trientine hydrochloride or 500 mg of penicillamine. Although Syprine appeared to be less potent than penicillamine on a molar basis, the data showed that Syprine is efficacious as a cupriuretic drug in patients with Wilson disease. According to data from research conducted with radioactively labeled copper, the differences in the cupriuretic effects of these 2 medications may be based on differences in their selectivity for various pools of copper pools inside the body.2

In animal studies, Syprine has demonstrated cupriuretic properties in both normal and copper-loaded rats. Even though the rates of urinary copper excretion were much lower in one investigation, the effects of trientine hydrochloride on urinary copper excretion are generally comparable with those of equimolar doses of penicillamine.5

Warnings, Precautions, and Adverse Effects

Trientine hydrochloride has not been associated with hypersensitivity reactions in any of the patients treated for Wilson disease, although asthma, bronchitis, and dermatitis have been reported in individuals exposed to trientine hydrochloride for a long time when they work in environments where it is used as a hardener of epoxy resins. Patients must be monitored continuously for indications of potential hypersensitivity.2 

Patients should be advised not to take mineral supplements while undergoing treatment with Syprine because its absorption can be reduced, and to inform their physicians if they are pregnant, plan to become pregnant, or are breastfeeding.3 

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Patients should be instructed to take their temperature every night for the first month of treatment, and to mention any symptoms such a fever or skin rash.2 While using Syprine, they should continue to receive their usual medical care. A check to detect iron deficiency anemia is done regularly, especially in women.3 

The level of free copper in the serum, which is equal to the difference between the quantitatively determined levels of total copper and ceruloplasmin-copper, is the most reliable indicator for monitoring treatment. The serum free copper concentrations of patients who receive appropriate treatment are frequently less than 10 µg/dL. Every 6 to 12 months, the effects of treatment should be evaluated with a 24-hour urinary copper study.4 

Adverse reactions that have been noted with Syprine include iron deficiency, systemic lupus erythematosus, dystonia, muscular spasm, and myasthenia gravis.4 

References

  1. Generic Syprine availability. Drugs.com. Updated September 8, 2022. Accessed September 28, 2022.
  2. SYPRINE- trientine hydrochloride capsule. DailyMed. Updated September 1, 2020. Accessed September 28, 2022.
  3. Syprine. Bausch Health. Accessed September 28, 2022.
  4. Syprine. Rxlist.com. Updated May 9, 2022. Accessed September 28, 2022.
  5. Syprine® (trientine hydrochloride) capsules. Package insert. Bausch Health; 2020. Accessed September 28, 2022.

Reviewed by Kyle Habet, MD, on 10/27/2022.

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