TRIENTINE HYDROCHLORIDE (Page 2 of 2)

CONTRAINDICATIONS

Hypersensitivity to this product.

WARNINGS

Patient experience with trientine hydrochloride is limited (see CLINICAL PHARMACOLOGY). Patients receiving trientine hydrochloride should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia.

PRECAUTIONS

GENERAL PRECAUTIONS

There are no reports of hypersensitivity in patients who have been administered trientine hydrochloride for Wilson’s disease. However, there have been reports of asthma, bronchitis and dermatitis occurring after prolonged environmental exposure in workers who use trientine hydrochloride as a hardener of epoxy resins. Patients should be observed closely for signs of possible hypersensitivity.

INFORMATION FOR PATIENTS

Patients should be directed to take trientine hydrochloride capsules 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. Because of the potential for contact dermatitis, any site of exposure to the capsule contents should be washed with water promptly. For the first month of treatment, the patient should have his temperature taken nightly, and he should be asked to report any symptom such as fever or skin eruption.

LABORATORY TESTS

The most reliable index for monitoring treatment is the determination of free copper in the serum, which equals the difference between quantitatively determined total copper and ceruloplasmin-copper. Adequately treated patients will usually have less than 10 mcg free copper/dL of serum. Therapy may be monitored with a 24-hour urinary copper analysis periodically (i.e., every 6 to 12 months). Urine must be collected in copper-free glassware. Since a low copper diet should keep copper absorption down to less than one milligram a day, the patient probably will be in the desired state of negative copper balance if 0.5 to 1.0 mg of copper is present in a 24-hour collection of urine.

DRUG INTERACTIONS

In general, mineral supplements should not be given since they may block the absorption of trientine hydrochloride. 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 each inhibit absorption of the other, two hours should elapse between administration of trientine hydrochloride and iron. It is important that trientine hydrochloride 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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

Data on carcinogenesis, mutagenesis, and impairment of fertility are not available.

PREGNANCY

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. Trientine hydrochloride 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 trientine hydrochloride is administered to a nursing mother.

PEDIATRIC USE

Controlled studies of the safety and effectiveness of trientine hydrochloride 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 trientine hydrochloride 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 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 REACTIONS, contact Hetero Labs Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 & 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 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 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- to 12-month intervals (see PRECAUTIONS, Laboratory Tests ).
It is important that trientine hydrochloride capsules 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.

HOW SUPPLIED

Trientine hydrochloride capsules USP, 250 mg, are purple opaque cap/purple opaque body size ‘1’ hard gelatin capsules imprinted with ‘H’ on cap and ‘T4’ on the body with black ink, filled with white to pale yellow powder. They are supplied as follows:
Bottles of 100 NDC 31722-683-01

STORAGE
Keep container tightly closed.

Store at 2° to 8°C (36° to 46°F).

Manufactured for:
Camber Pharmaceuticals, Inc.,
Piscataway, NJ 08854

Manufactured by:
HETERO ^TM
HETERO LABS LIMITED
22-110, I.D.A., Jeedimetla,
Hyderabad — 500 055, India. Issued: 07/2022

PACKAGE LABEL PRINCIPAL DISPLAY PANEL

Trientine Hydrochloride Capsules USP 250 mg- Container Carton Label

Trientine Hydrochloride Capsules USP 250 mg- Container Label

TRIENTINE HYDROCHLORIDE trientine hydrochloride capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:31722-683 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (TRIENTINE) TRIENTINE HYDROCHLORIDE 250 mg

Inactive Ingredients Ingredient Name Strength STEARIC ACID D&C RED NO. 28 FD&C BLUE NO. 1 GELATIN TITANIUM DIOXIDE FERROSOFERRIC OXIDE POTASSIUM HYDROXIDE PROPYLENE GLYCOL SHELLAC AMMONIA

Product Characteristics Color purple (opaque) Score no score Shape CAPSULE Size 20mm Flavor Imprint Code H;T4 Contains

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:31722-683-01 1 BOTTLE in 1 CARTON contains a BOTTLE 1 100 CAPSULE in 1 BOTTLE This package is contained within the CARTON (31722-683-01)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA216356 06/23/2022

Labeler — Camber Pharmaceuticals, Inc. (826774775)

Establishment
Name	Address	ID/FEI	Operations
Hetero Labs Limited Unit III		676162024	manufacture (31722-683)

Revised: 08/2022 Camber Pharmaceuticals, Inc.