Triethylenetetramine (Trientine): A Comprehensive Pharmacological and Clinical Review

I. Introduction and Overview of Triethylenetetramine

Triethylenetetramine (TETA), known by its International Nonproprietary Name (INN) trientine, is a chelating agent with a primary, well-established role in the management of Wilson's disease.[1] Wilson's disease is an autosomal recessive genetic disorder characterized by the pathological accumulation of copper in various tissues, most notably the liver and brain, leading to hepatic, neurological, and psychiatric manifestations if untreated.[3] Trientine is specifically indicated for patients with Wilson's disease who are intolerant to D-penicillamine, the traditional first-line chelator, or for whom penicillamine therapy is otherwise clinically inappropriate.[1]

The development of TETA dates back to its first synthesis in Germany in 1861, with its chelating properties being recognized in 1925.[1] Its entry into clinical practice for Wilson's disease was marked by the FDA approval of trientine hydrochloride (Syprine®) in 1985 as a second-line treatment.[1] This provided a critical therapeutic alternative for a subset of Wilson's disease patients. More recently, advancements in formulation have led to the development and approval of trientine tetrahydrochloride (e.g., Cuvrior®, Cuprior®), which offers improved room temperature stability, a significant advantage for a medication requiring lifelong administration.[9] This evolution in formulation underscores a continuous effort to enhance patient convenience and potentially adherence, which are paramount in the chronic management of Wilson's disease. The stability of the tetrahydrochloride salt, not requiring refrigeration unlike some earlier dihydrochloride preparations, directly addresses a practical barrier to consistent medication use, thereby potentially improving long-term disease control.[9]