Trientine

Primary drug AGALSIDASE Secondary drug Effect Mechanism Precautions 

AGALSIDASE BETA ANTIARRHYTHMICS -AMIODARONE 1 clinical effect of agalsidase beta Uncertain Avoid co-administration 

AGALSIDASE BETA ANTIMALARIALS -CHLOROQUINE L efficacy of agalsidase beta Inhibition of intracellular activity of agalsidase beta Avoid co-administration -manufacturers recommendation 

LARONIDASE ANAESTHETICS-LOCAL-procaine Possibly l efficacy of laronidase Uncertain Avoid co-administration 

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Triethylenetetramine (TRIEN, TETA, trientine) [112-24-3] M 146.2, m 12°, b 157°/20mm, d 0.971, n 1.497, pK 3.32, pKj 6.67, pKj 9.20, pK 9.92. Dried with sodium, then distd under vac. Further purification has been via the nitrate or the chloride. For example, Jonassen and Strickland [J Am Chem Soc 80 312 1958] separated TRIEN from admixture with TREN (38%) by soln in EtOH, cooling to approximately 5° in an ice-bath and adding cone HCl dropwise from a burette, keeping the temperature below 10°, until all of the white crystalline ppte of TREN.HCl had formed and been removed. Further addition of HCl then ppted thick creamy white TRIEN.HCl which was crystd several times from hot water by adding an excess of cold EtOH. The crystals were finally washed with Me2CO, then Et20 and dried in a vacuum desiccator. 

C2H4CI2 107-06-2) see Dofetilide Ethambutol Trientine 2 ,4 -dichloro-5 -fluoroacetophenone (CJH5CI2FO 704-10-9) see Temafloxacin... 

Treatment. Since the 1950s, the treatment of Wilson s disease has relied on chelating agents [25]. Early attempts to use BAL or EDTA for this purpose were unsuccessful, but penicillamine, triethylene tetramine dihydrochloride (trientine), and tetrathiomolybdate, all in combination with a low-copper diet, have proved to be effective, and result in the urinary excretion of large amounts of copper. The use of penicillamine is complicated by the fact that it may induce a transient worsening of neurologic function due to rapid mobilization of copper, and also has other side-effects, such as the development of nephrosis. Tetrathiomolybdate is an effective alternative with fewer side-effects [26]. In cases in which the dose was rapidly escalated, however, bone marrow suppression or liver function abnormalities have been described. 

Iron salts may be affected by the following agents AHA, antacids, ascorbic acid, calcium salts, chloramphenicol, digestive enzymes, H2 antagonists, proton pump inhibitors, tetracyclines, and trientine. 

Pharmacology Wilson disease (hepatolenticular degeneration) is an inherited metabolic defect resulting in excess copper accumulation, possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper, but when their capacity is exceeded, copper is released into the blood and is taken up into extrahepatic sites. Treat this condition with a low copper diet and chelating agents that bind copper to facilitate its excretion from the body. Trientine is a chelating compound for removal of excess copper from the body. 

Children Safety and efficacy for use in children have not been established. Trientine has been used clinically in children as young as 6 years of age with no reported adverse effects. 

Hypersensitivity There are no reports of hypersensitivity in patients given trientine for Wilson disease. However, there have been reports of asthma, bronchitis, and dermatitis occurring after prolonged environmental exposure in workers who use trientine as a hardener of epoxy resins. Observe patients closely for signs of possible hypersensitivity. 

Mineral supplements In general, do not give mineral supplements they may block the absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson disease. If necessary, iron may be given in short courses, but because iron and trientine each inhibit absorption of the other, allow 2 hours to elapse between administration of trientine and iron. 

For patients who are unable to tolerate penicillamine, trientine, another chelating agent, may be used in a daily dose of 1-1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Zinc acetate administered orally increases the fecal excretion of copper and is sometimes used for maintenance therapy. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced. 

Walshe JM (1982) Treatment of Wilson s disease with trientine (triethylene tetramine) dihydrochloride. Lancet, 319 643-647... 

Treatment While damage cannot be cured, disease progression can be slowed down by lifelong chelation therapy. These chelating agents (including d-penicillamine or trientine hydrochloride) can help remove copper from tissue, and zinc supplements may help slow copper absorption, but patients also need to follow a diet low in copper. In extreme conditions where patients do not respond to treatment, liver transplantation may be an option. 

ANTACIDS-CALCIUM-AND MAGNESIUM-CONTAINING TRIENTINE Possibly 1 trientine levels i absorption Separate doses as much as possible take antacids after trientine... 

TRIENTINE IRON-ORAL l iron levels when iron is given orally i absorption Separate doses by at least 2 hours -monitor FBC closely... 

Trientine (triethylenetetramine) was used in 1982 to treat Wilson disease as an alternative to D-peiticillamtne. It is also a chelator of copper and increases urinary excretion of copper. There is less experience with the use of trientine compared to D-penicillamine. Its toxicity is relatively unexplored. The initial effect of this treatment is large cupriuresis but its rate diminishes more rapidly than with D-penicillamine. However, it should be pointed out that this treatment is effective especially in situations for which D-penicillamine must be... 

Molybdate is known to induce copper deficiency, ft was found that the administration of molybdenum compounds, particularly with added sulfate, impaired copper metabolism in ruminants. Tetrathiomolybdate has been used to treat patients who were intolerant to D-penicillanune, trientine, and zinc. Tetrathiomolybdate seems to act both by blocking the intestinal absorption of copper and keeping it in a metabolically inert chelated form, which is not taken up by the liver. However, it induces only a modest cupriuresis. There are also known toxic effects of tetrathiomolybdate on the skeletal system of growing animals. Thus one should be extremely careful in administering this compound. It should be considered as an experimental drug. 

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