Tag Archives: Trientine

How Trientine and Penicillamine Work: Cool Visual Study

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FT Kirk et al. Hepatology 2024; 79: 1065-1074. Open Access! Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans

Background: Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN.

Key findings and conclusions:

  • “TRI inhibits intestinal copper absorption, in addition to its cupriuretic effect. In contrast, PEN has modest effects on the intestinal copper absorption. This may explain why TRI and PEN are equally effective although urinary copper excretion is lower with TRI.”
  • ” TRI (n=8) reduced hepatic 64Cu activity 1 hour after 64Cu dose from 6.17 (4.73) to 1.47 (2.97) standard uptake value, p<0.02, and after 15 hours from 14.24 (3.09) to 6.19 (3.43), p<0.02, indicating strong inhibition of intestinal 64Cu absorption.”
  • “PEN (n=8) slightly reduced hepatic standard uptake value at 15 hours, from 16.30 (5.63) to 12.17 (1.44), p<0.04.”
  • “The study questions whether the same therapeutic targets for 24-hour urinary excretion apply to both drugs.”

My take: This is a cool study!

Related blog post: Practice Guidance on Wilson Disease (AASLD) (2023)

“This Is A Stick Up — Your Money or Your Life”

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When I read a recent Hepatology editorial (Hepatology 2015; 61: 1106-8), I could not help think of the aforementioned title of this blog.

Here’s the scoop:

The two most commonly used medications for Wilson’s disease are trientine (Syprine) and D-penicillamine (Cupramine). For about 20 years, the original manufacturer of these medications kept the consumer cost at ~$1 per 250 mg tablet.  Currently the cost of Syprine is ~$200 per 250 mg tablet and Cuprimine costs ~$55 per 250 mg tablet.  This 200-fold increase translates into a yearly cost of ~$300,000.

How did this happen?

  • Little competition
  • Profit motive
  • Patients are reluctant to protest (they need this medication to be manufactured)

Why is this outrageous?

This increase in cost was not driven by any new discovery or research innovation.

Are there options?

Zinc is inexpensive and may be an option after initial period of chelation/normalization of liver biochemistries.  Zinc needs to be taken two to three times per day and “well away from meals for best absorption.”

Bottomline: These medication prices are outrageous.

Briefly noted:

  • “Molecular pathophysiology of portal hypertension”  Hepatology 2015; 61: 1406-15. Terrific review with excellent figures.
  • “Ezetimibe for the treatment of Nonacloholic Steatohepatitis” (MOZART trial) Hepatology 2015; 61: 1239-50. This randomized double-blind, placebo-controlled trial with 50 patients (biopsy-proven NASH) showed that Ezetimbe was not significantly different from placebo in histologic response rates, serum aminotransferases, or in magnetic resonance elastography findings.
  • Van Biervliet et al. “Clinical Zinc Deficiency as Early Presentation of Wilson Disease” JPGN 2015; 60: 457-9. Case report.

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Data on Chelators for Wilson Disease

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A recent retrospective analysis on 405 patients with Wilson disease analyzed the efficacy and safety of oral chelators for Wilson disease (Clin Gastroenterol Hepatol 2013; 11: 1028-35).

The authors noted that there were frequent changes in medication; in total, 471 monotherapies were analyzed: 326 patients with D-penicillamine (DPA) and 141 with trientine.  Trientine was a first line treatment in only 38 patients.  About 50% of patients presented with hepatic symptoms, about 20% neurologic symptoms, about 15% with combined hepatic/neurologic symptoms and the remainder, ~10%, were asymptomatic.

  • 9 of 326 with DPA and 3 of 141 with trientine underwent liver transplantation.
  • Adverse effects were more common with DPA, including arthralgias (8.9%), proteinuria (6.1%), ANA antibodies (6.7%), gastric complaints (2.5%) and polyneuropathy (1.8%).  28.8% of DPA stopped therapy due to adverse effects.
  • Adverse effects with trientine resulted in stopping treatment in 7.1% and included arthralgias in 2.8%, and gastric complaints in 1.4%.
  • Hepatic improvements were observed in >90%

The authors summarize their findings:

“Both DPA and trientine were equally and highly effective in controlling liver disease…In light of recent reports of hepatic deterioration under zinc therapy, the current data emphasize the role of these chelating agents in the treatment of symptomatic hepatic patients.”

Related blog post:

Finding the Right Specialist | gutsandgrowth This post has link to AASLD guidelines for Wilson disease.