educes the likelihood of inactivation of the drug by metal binding in the gastrointestinal tract.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Data on carcinogenesis, mutagenesis, and impairment of fertility are not available.
Pregnancy
Pregnancy Category C
Trientine hydrochloride was teratogenic in rats at doses similar to the human dose. The frequencies of both resorptions and fetal abnormalities, including hemorrhage and edema, increased while fetal copper levels decreased when trientine hydrochloride was given in the maternal diets of rats. There are no adequate and well-controlled studies in pregnant women. SYPRINE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SYPRINE is administered to a nursing mother.
Pediatric Use
Controlled studies of the safety and effectiveness of SYPRINE in pediatric patients have not been conducted. It has been used clinically in pediatric patients as young as 6 years with no reported adverse experiences.
Geriatric Use
Clinical studies of SYPRINE did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience is insufficient to determine differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
Clinical experience with SYPRINE has been limited. The following adverse reactions have been reported in a clinical study in patients with Wilson's disease who were on therapy with trientine hydrochloride: iron deficiency, systemic lupus erythematosus (see CLINICAL PHARMACOLOGY). In addition, the following adverse reactions have been reported in marketed use: dystonia, muscular spasm, myasthenia gravis.
SYPRINE is not indicated for treatment of biliary cirrhosis, but in one study of 4 patients treated with trientine hydrochloride for primary biliary cirrhosis, the following adverse reactions were reported: heartburn; epigastric pain and tenderness; thickening, fissuring and flaking of the skin; hypochromic microcytic anemia; acute gastritis; aphthoid ulcers; abdominal pain; melena; anorexia; malaise; cramps; muscle pain; weakness; rhabdomyolysis. A causal relationship of these reactions to drug therapy could not be rejected or established.
OVERDOSAGE
There is a report of an adult woman who ingested 30 grams of trientine hydrochloride without apparent ill effects. No other data on overdosage are available.
DOSAGE AND ADMINISTRATION
Systemic eva luation of dose and/or interval between dose has not been done. However, on limited clinical experience, the recommended initial dose of SYPRINE is 500-750 mg/day for pediatric patients and 750-1250 mg/day for adults given in divided doses two, three or four times daily. This may be increased to a maximum of 2000 mg/day for adults or 1500 mg/day for pediatric patients age 12 or under.
The daily dose of SYPRINE should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dL. |
