Trientine Hydrochloride

INDICATIONS AND USAGE Trientine hydrochloride capsules USP 250 mg is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with trientine hydrochloride capsules USP 250 mg is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defined. Trientine hydrochloride capsules USP 250 mg and penicillamine cannot be considered interchangeable. Trientine hydrochloride capsules USP 250 mg should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects. Unlike penicillamine, trientine hydrochloride capsules USP 250 mg is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, trientine hydrochloride capsules USP 250 mg was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment. Trientine hydrochloride capsules USP 250 mg is not indicated for treatment of biliary cirrhosis.

DOSAGE AND ADMINISTRATION Systemic evaluation of dose and/or interval between dose has not been done. However, on limited clinical experience, the recommended initial dose of trientine hydrochloride capsules USP 250 mg is 500 to 750 mg/day for pediatric patients and 750 to 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 trientine hydrochloride capsules USP 250 mg should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dL. Optimal long-term maintenance dosage should be determined at 6-12 month intervals (see PRECAUTIONS , Laboratory Tests ). It is important that trientine hydrochloride capsules USP 250 mg be given on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed.

CONTRAINDICATIONS Hypersensitivity to this product.

ADVERSE REACTIONS Clinical experience with trientine hydrochloride 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. Trientine hydrochloride 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. To report SUSPECTED ADVERSE EVENTS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

Drug Interactions In general, mineral supplements should not be given since they may block the absorption of Trientine Hydrochloride Capsule. 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's disease. If necessary, iron may be given in short courses, but since iron and Trientine Hydrochloride Capsule each inhibit absorption of the other, two hours should elapse between administration of Trientine Hydrochloride Capsule and iron. It is important that Trientine Hydrochloride Capsule be taken on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation of the drug by metal binding in the gastrointestinal tract.

DESCRIPTION Trientine hydrochloride is N,N' -bis (2-aminoethyl)-1,2-ethanediamine dihydrochloride. It is a white to pale yellow crystalline hygroscopic powder. It is freely soluble in water, soluble in methanol, slightly soluble in ethanol, and insoluble in chloroform and ether. The empirical formula is C 6 H 18 N 4 •2HCl with a molecular weight of 219.2. The structural formula is: NH 2 (CH 2 ) 2 NH(CH 2 ) 2 NH(CH 2 ) 2 NH 2 •2HCl Trientine hydrochloride is a chelating compound for removal of excess copper from the body. Trientine hydrochloride is available as 250 mg capsules for oral administration. Trientine hydrochloride capsules USP, 250 mg contain stearic acid. In addition, the empty hard gelatin capsule shells contain gelatin, iron oxide black, iron oxide red, iron oxide yellow and titanium dioxide. The capsule shells are imprinted with TEK black ink containing butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac and strong ammonia solution.

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.

HOW SUPPLIED Trientine Hydrochloride Capsule, USP 250 mg, are Size “1” hard gelatin capsule with brown opaque cap/brown opaque body, imprinted “C27” on cap with black ink and “250mg” on body with black ink filled with white to pale yellow powder. They are supplied as follows: NDC 16571-810-01 Bottles of 100 Capsules. Trientine Hydrochloride Capsule, USP 500 mg, are Size “00” hard gelatin capsule with brown opaque cap/ brown opaque body, imprinted “C28” on cap with black ink and “500 mg” on body with black ink filled with white to pale yellow powder. They are supplied as follows: NDC 16571-812-05 Bottles of 50 Capsules. Storage Keep container tightly closed. Store below 25°C (77°F). Store Trientine hydrochloride capsules in its original container. Manufactured for: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Made in India Neutral Code: 4323147/TS/DRUGS/2025 Revised: 08/2025 PIR81205-01