- Description
- Clinical Pharmacology
- Indications And Usage
- Contraindications
- Warnings
- Precautions
- Adverse Reactions
- Overdosage
- Dosage And Administration
- How Supplied
- Label And Carton
- Storage
- Package Label.principal Display Panel
- Indications And Usage
- Dosage And Administration
- Description
- Clinical Pharmacology
- Indications And Usage
- Contraindications
- Warnings
- Precautions
- Adverse Reactions
- Overdosage
- Dosage And Administration
- How Supplied
- Principal Display Panel - Bottle Label
- Trientine Hydrochloride Capsules, Usp Rx Only
- Carton Label
- Principal Display Panel
- Package Label Principal Display Panel Section
- Principal Display Panel - 250 Mg Capsule Carton
Description ⮝
Trientine hydrochloride, USP 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 molecular formula is C6H18N4 2HCl with a molecular weight of 219.16. The structural formula is:
Trientine hydrochloride is a chelating compound for removal of excess copper from the body. Trientine hydrochloride capsules, USP intended for oral administration contains 250 mg of trientine hydrochloride, USP and contains following inactive ingredients: gelatin, iron oxide red, iron oxide yellow, stearic acid, and titanium dioxide.
The capsule is imprinted with black pharmaceutical ink and contains following inactive ingredients: black iron oxide, potassium hydroxide, propylene glycol, purified water and shellac.
Clinical Pharmacology ⮝
Introduction
Wilson's disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates 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. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body.
Clinical Summary
Forty-one patients (18 male and 23 female) between the ages of 6 and 54 with a diagnosis of Wilson's disease and who were intolerant of d-penicillamine were treated in two separate studies with trientine hydrochloride. The dosage varied from 450 mg to 2,400 mg per day. The average dosage required to achieve an optimal clinical response varied between 1,000 mg and 2,000 mg per day. The mean duration of trientine hydrochloride therapy was 48.7 months (range 2 months to 164 months). Thirty-four of the 41 patients improved, 4 had no change in clinical global response, 2 were lost to follow-up and one showed deterioration in clinical condition. One of the patients who improved while on therapy with trientine hydrochloride experienced a recurrence of the symptoms of systemic lupus erythematosus which had appeared originally during therapy with penicillamine. Therapy with trientine hydrochloride was discontinued. No other adverse reactions, except iron deficiency, were noted among any of these 41 patients.
One investigator treated 13 patients with trientine hydrochloride following their development of intolerance to d penicillamine. Retrospectively, he compared these patients to an additional group of 12 patients with Wilson's disease who were both tolerant of and controlled with d-penicillamine therapy, but who failed to continue any copper chelation therapy. The mean age at onset of disease of the latter group was 12 years as compared to 21 years for the former group. The trientine hydrochloride group received d-penicillamine for an average of 4 years as compared to an average of 10 years for the non-treated group.
Various laboratory parameters showed changes in favor of the patients treated with trientine hydrochloride. Free and total serum copper, SGOT and serum bilirubin all showed mean increases over baseline in the untreated group which were significantly larger than with the patients treated with trientine hydrochloride. In the 13 patients treated with trientine hydrochloride, previous symptoms and signs relating to d-penicillamine intolerance disappeared in 8 patients, improved in 4 patients, and remained unchanged in one patient. The neurological status in the trientine hydrochloride group was unchanged or improved over baseline, whereas in the untreated group, 6 patients remained unchanged and 6 worsened. Kayser-Fleischer rings improved significantly during trientine hydrochloride treatment.
The clinical outcome of the two groups also differed markedly. Of the 13 patients on therapy with trientine hydrochloride (mean duration of therapy 4.1 years; range 1 years to 13 years), all were alive at the data cutoff date, and in the non-treated group (mean years with no therapy 2.7 years; range 3 months to 9 years), 9 of the 12 died of hepatic disease.
Chelating Properties
Studies in animals have shown that trientine hydrochloride has cupriuretic activities in both normal and copper loaded rats. In general, the effects of trientine hydrochloride on urinary copper excretion are similar to those of equimolar doses of penicillamine, although in one study they were significantly smaller.
Human Studies
Renal clearance studies were carried out with penicillamine and trientine hydrochloride on separate occasions in selected patients treated with penicillamine for at least one year. Six hour excretion rates of copper were determined off treatment and after a single dose of 500 mg of penicillamine or 1.2 g of trientine hydrochloride. The mean urinary excretion rates of copper were as follows:
No. of
Patients
Single Dose Treatment
Basal Excretion Rate
(mcg Cu ++ /6hr)
Test-dose Excretion Rate
(mcg Cu++/6hr)
6
Trientine, 1.2 g
19
234
4
Penicillamine, 500 mg
17
320
In patients not previously treated with chelating agents, a similar comparison was made:
No. of
Patients
Single Dose Treatment
Basal Excretion Rate
(mcg Cu ++ /6hr)
Test-dose Excretion Rate
(mcg Cu++/6hr)
8
Trientine, 1.2 g
71
1,326
7
Penicillamine, 500 mg
68
1,074
These results demonstrate that trientine hydrochloride is effective as a cupriuretic agent in patients with Wilson's disease although on a molar basis it appears to be less potent or less effective than penicillamine. Evidence from a radio-labelled copper study indicates that the different cupriuretic effect between these two drugs could be due to a difference in selectivity of the drugs for different copper pools within the body.
Pharmacokinetics
Data on the pharmacokinetics of trientine hydrochloride are not available. Dosage adjustment recommendations are based upon clinical use of the drug (see DOSAGE AND ADMINISTRATION).
Indications And Usage ⮝
Trientine hydrochloride capsules are indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with trientine hydrochloride capsules is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defmed. Trientine hydrochloride capsules and penicillamine cannot be considered interchangeable. Trientine hydrochloride capsules 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 are 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 was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.
Trientine hydrochloride capsules are not indicated for treatment of biliary cirrhosis.
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
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 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 months 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 milligram 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 Zydus Pharmaceuticals USA Inc. at 1-877-993-8779 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 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 are 500 mg/day to 750 mg/day for pediatric patients and 750 mg/day to 1,250 mg/day for adults given in divided doses two, three or four times daily. This may be increased to a maximum of 2,000 mg/day for adults or 1,500 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 month 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 white to pale yellow-colored crystalline powder filled in size '1' capsule having an opaque light brown cap printed with '1203' in black ink and an opaque white body and are supplied as follows:
NDC 70771-1438-1 in bottles of 100 capsules with child-resistant closure.
STORAGE
Keep container tightly closed.
Store at 2 to 8 C (36 to 46 F).
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Cadila Healthcare Limited
Ahmedabad, India.
Rev.: 03/18
Label And Carton ⮝
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:49884-060 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (UNII: HC3NX54582) (TRIENTINE - UNII:SJ76Y07H5F) TRIENTINE HYDROCHLORIDE 250 mg
Inactive Ingredients Ingredient Name Strength GELATIN (UNII: 2G86QN327L) FERRIC OXIDE RED (UNII: 1K09F3G675) FERROSOFERRIC OXIDE (UNII: XM0M87F357) FERRIC OXIDE YELLOW (UNII: EX438O2MRT) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) BUTYL ALCOHOL (UNII: 8PJ61P6TS3) ALCOHOL (UNII: 3K9958V90M) ISOPROPYL ALCOHOL (UNII: ND2M416302) POTASSIUM HYDROXIDE (UNII: WZH3C48M4T) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) SHELLAC (UNII: 46N107B71O) AMMONIA (UNII: 5138Q19F1X)
Product Characteristics Color BROWN (light brown opaque) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code PAR;060 Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:49884-060-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/27/2019
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA210096 09/27/2019
Labeler - Par Pharmaceutical, Inc. (092733690) Revised: 6/2017 Document Id: 8e8769ab-bd38-47df-b878-b0c5f48b209e Set id: 431c7f66-d58b-4eb0-b195-d164788f9acf Version: 5 Effective Time: 20170620 Par Pharmaceutical, Inc.
Storage ⮝
Dispense in a tight container and store in a refrigerator; 2 to 8 C (36 to 46 F). Keep container tightly closed.
Distributed by:
Ewing, NJ 08618
Made in India
Rev. 02/2019
31010119 R0
Package Label.principal Display Panel ⮝
Trientine Hydrochloride Capsules, USP 250 mg
100 Capsules
Rx only
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:70771-1438 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (UNII: HC3NX54582) (TRIENTINE - UNII:SJ76Y07H5F) TRIENTINE HYDROCHLORIDE 250 mg
Inactive Ingredients Ingredient Name Strength FERRIC OXIDE RED (UNII: 1K09F3G675) FERRIC OXIDE YELLOW (UNII: EX438O2MRT) FERROSOFERRIC OXIDE (UNII: XM0M87F357) GELATIN (UNII: 2G86QN327L) POTASSIUM HYDROXIDE (UNII: WZH3C48M4T) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) SHELLAC (UNII: 46N107B71O) STEARIC ACID (UNII: 4ELV7Z65AP) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) WATER (UNII: 059QF0KO0R)
Product Characteristics Color BROWN (light brown cap) , WHITE (white body) Score no score Shape CAPSULE Size 20mm Flavor Imprint Code 1203 Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:70771-1438-1 1 in 1 CARTON 04/29/2019 1 100 in 1 BOTTLE; Type 0: Not a Combination Product
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA211554 04/29/2019
Labeler - Cadila Healthcare Limited (918596198)
Registrant - Cadila Healthcare Limited (918596198)
Establishment Name Address ID/FEI Business Operations Cadila Healthcare Limited 863362789 ANALYSIS(70771-1438) , MANUFACTURE(70771-1438) Revised: 4/2019 Document Id: 2b849c67-13ba-4de7-be28-3aa7a7151ec0 Set id: e7950a50-7528-4458-8b3a-34bb1662f83b Version: 1 Effective Time: 20190429 Cadila Healthcare Limited
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.
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 C6H18N4 2HCl with a molecular weight of 219.2. The structural formula is:
NH2(CH2)2NH(CH2)2NH(CH2)2NH2 2HCl
Trientine hydrochloride is a chelating compound for removal of excess copper from the body. Trientine Hydrochloride Capsules, USP are available as 250 mg capsules for oral administration. Each capsule contains 250 mg trientine hydrochloride, USP and the inactive ingredient stearic acid. The capsule shell consists of gelatin and titanium dioxide. The capsule shell ink contains shellac, titanium dioxide, FD&C yellow #5 aluminum lake, FD&C blue #1 aluminum lake, FD&C blue#2/indigo carmine aluminum lake, and FD&C blue #1/brilliant blue FCF aluminum lake.
Clinical Pharmacology ⮝
Introduction
Wilson s disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates 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. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body.
Clinical Summary
Forty-one patients (18 male and 23 female) between the ages of 6 and 54 with a diagnosis of Wilson s disease and who were intolerant of d-penicillamine were treated in two separate studies with trientine hydrochloride. The dosage varied from 450 to 2400 mg per day. The average dosage required to achieve an optimal clinical response varied between 1000 mg and 2000 mg per day. The mean duration of trientine hydrochloride therapy was 48.7 months (range 2-164 months). Thirty-four of the 41 patients improved, 4 had no change in clinical global response, 2 were lost to follow-up and one showed deterioration in clinical condition. One of the patients who improved while on therapy with trientine hydrochloride experienced a recurrence of the symptoms of systemic lupus erythematosus which had appeared originally during therapy with penicillamine. Therapy with trientine hydrochloride was discontinued. No other adverse reactions, except iron deficiency, were noted among any of these 41 patients.
One investigator treated 13 patients with trientine hydrochloride following their development of intolerance to d-penicillamine. Retrospectively, he compared these patients to an additional group of 12 patients with Wilson s disease who were both tolerant of and controlled with d-penicillamine therapy, but who failed to continue any copper chelation therapy. The mean age at
onset of disease of the latter group was 12 years as compared to 21 years for the former group. The trientine hydrochloride group received d-penicillamine for an average of 4 years as compared to an average of 10 years for the non-treated group.
Various laboratory parameters showed changes in favor of the patients treated with trientine hydrochloride. Free and total serum copper, SGOT, and serum bilirubin all showed mean increases over baseline in the untreated group which were significantly larger than with the patients treated with trientine hydrochloride. In the 13 patients treated with trientine hydrochloride, previous symptoms and signs relating to d-penicillamine intolerance disappeared in 8 patients, improved in 4 patients, and remained unchanged in one patient. The neurological status in the trientine hydrochloride group was unchanged or improved over baseline, whereas in the untreated group, 6 patients remained unchanged and 6 worsened. Kayser-Fleischer rings improved significantly during trientine hydrochloride treatment.
The clinical outcome of the two groups also differed markedly. Of the 13 patients on therapy with trientine hydrochloride (mean duration of therapy 4.1 years; range 1 to 13 years), all were alive at the data cutoff date, and in the non-treated group (mean years with no therapy 2.7 years; range 3 months to 9 years), 9 of the 12 died of hepatic disease.
Chelating Properties
Preclinical Studies
Studies in animals have shown that trientine hydrochloride has cupriuretic activities in both normal and copper-loaded rats. In general, the effects of trientine hydrochloride on urinary copper excretion are similar to those of equimolar doses of penicillamine, although in one study they were significantly smaller.
Human Studies
Renal clearance studies were carried out with penicillamine and trientine hydrochloride on separate occasions in selected patients treated with penicillamine for at least one year. Six-hour excretion rates of copper were determined off treatment and after a single dose of 500 mg of penicillamine or 1.2 g of trientine hydrochloride. The mean urinary excretion rates of copper were as follows:
No. of Patients
Single Dose Treatment
Basal Excretion Rate
(mcg Cu + + /6hr)Test-dose Excretion Rate
(mcg Cu + + /6hr)6
Trientine, 1.2 g
19
234
4
Penicillamine, 500 mg
17
320
In patients not previously treated with chelating agents, a similar comparison was made:
No. of Patients
Single Dose Treatment
Basal Excretion Rate
(mcg Cu + + /6hr)Test-dose Excretion Rate
(mcg Cu + + /6hr)8
Trientine, 1.2 g
71
1326
7
Penicillamine, 500 mg
68
1074
These results demonstrate that Trientine hydrochloride is effective as a cupriuretic agent in patients with Wilson s disease although on a molar basis it appears to be less potent or less effective than penicillamine. Evidence from a radio-labelled copper study indicates that the different cupriuretic effect between these two drugs could be due to a difference in selectivity of the drugs for different copper pools within the body.
Pharmacokinetics
Data on the pharmacokinetics of trientine hydrochloride are not available. Dosage adjustment recommendations are based upon clinical use of the drug (see DOSAGE AND ADMINISTRATION).
Indications And Usage ⮝
Trientine hydrochloride is indicated in the treatment of patients with Wilson s disease who are intolerant of penicillamine. Clinical experience with Trientine hydrochloride 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 and penicillamine cannot be considered interchangeable. Trientine hydrochloride should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.
Unlike penicillamine, trientine hydrochloride 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 was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.
Trientine hydrochloride is not indicated for treatment of biliary cirrhosis.
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
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.
This product contains FD&C Yellow #5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow #5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Information for Patients
Patients should be directed to take trientine hydrochloride 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 6-12 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 milligram 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 Kadmon Pharmaceuticals, LLC at 1-877-377-7862 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 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 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 trientine hydrochloride 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 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 opaque white capsules coded KD034 250 mg on the body of the capsule printed in green ink and Kadmon on the cap of the capsule printed in blue ink. They are supplied as follows:
NDC 66435-700-10 in bottles of 100.
STORAGE
Keep container tightly closed.
Store at 2-8 C (36 F and 46 F).
Manufactured by:
Xcelience
Tampa, FL 33607, USAManufactured For:
Kadmon Pharmaceuticals, LLC
Warrendale, PA 15086, USAC151.00042
Rev. 12/2018
Principal Display Panel - Bottle Label ⮝
Bottle Label
NDC 66435-700-10 Rx only
Trientine Hydrochloride
Capsules, USP
250 mgEach capsule contains
trientine hydrochloride 250 mgKadmon
Pharmaceuticals, LLC 100 capsulesStore at 2-8 C (36-46 F).
Usual Dosage: See accompanying
prescribing information.Keep container tightly closed.
Dispense in tight container.
Contains FD&C Yellow No. 5
(tartrazine) as a color additive.Distributed by:
Kadmon Pharmaceuticals, LLC
Warrendale, PA 15086, USAManufactured by:
Xcelience
Tampa, FL 33607, USAProduct of the USA
C151.00038
70014020
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:66435-700 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (UNII: HC3NX54582) (TRIENTINE - UNII:SJ76Y07H5F) TRIENTINE HYDROCHLORIDE 250 mg
Inactive Ingredients Ingredient Name Strength GELATIN, UNSPECIFIED (UNII: 2G86QN327L) STEARIC ACID (UNII: 4ELV7Z65AP) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) SHELLAC (UNII: 46N107B71O) ALCOHOL (UNII: 3K9958V90M) ISOPROPYL ALCOHOL (UNII: ND2M416302) BUTYL ALCOHOL (UNII: 8PJ61P6TS3) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) AMMONIA (UNII: 5138Q19F1X) FD&C YELLOW NO. 5 (UNII: I753WB2F1M) FD&C BLUE NO. 1 (UNII: H3R47K3TBD) FD&C BLUE NO. 2 (UNII: L06K8R7DQK)
Product Characteristics Color WHITE (opaque) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code KD034;250mg;Kadmon Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:66435-700-10 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/30/2019
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA209415 09/30/2019
Labeler - Kadmon Pharmaceuticals, LLC (843913216) Revised: 9/2019 Document Id: d0dbfacd-8c38-40ed-b41e-cdb91b0cf1d8 Set id: f04c6ec0-4855-448e-b9f4-f361571f2860 Version: 2 Effective Time: 20190927 Kadmon Pharmaceuticals, LLC
Trientine Hydrochloride Capsules, Usp Rx Only ⮝
DESCRIPTION
Trientine hydrochloride, USP 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 6H 18N 4 2HCl with a molecular weight of 219.2. The structural formula is: NH 2(CH 2) 2NH(CH 2) 2NH(CH 2) 2NH 2 2HCl
Trientine hydrochloride (HCl), USP is a chelating compound for removal of excess copper from the body. Each trientine HCl capsule, USP for oral administration contains 250 mg of trientine HCl, USP with the following inactive ingredient: stearic acid. The hard gelatin capsule shells contain the following inactive ingredients: black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide. The black ink contains the following inactive ingredients: black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution.
CLINICAL PHARMACOLOGY
Introduction
Wilson s disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates 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. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body.
Clinical Summary
Forty-one patients (18 male and 23 female) between the ages of 6 and 54 with a diagnosis of Wilson s disease and who were intolerant of d-penicillamine were treated in two separate studies with trientine HCl. The dosage varied from 450 to 2,400 mg per day. The average dosage required to achieve an optimal clinical response varied between 1,000 mg and 2,000 mg per day. The mean duration of trientine HCl therapy was 48.7 months (range 2 to 164 months). Thirty-four of the 41 patients improved, 4 had no change in clinical global response, 2 were lost to follow-up and one showed deterioration in clinical condition. One of the patients who improved while on therapy with trientine HCl experienced a recurrence of the symptoms of systemic lupus erythematosus which had appeared originally during therapy with penicillamine. Therapy with trientine HCl was discontinued. No other adverse reactions, except iron deficiency, were noted among any of these 41 patients.
One investigator treated 13 patients with trientine HCl following their development of intolerance to d-penicillamine. Retrospectively, he compared these patients to an additional group of 12 patients with Wilson s disease who were both tolerant of and controlled with d-penicillamine therapy, but who failed to continue any copper chelation therapy. The mean age at onset of disease of the latter group was 12 years as compared to 21 years for the former group. The trientine HCl group received d-penicillamine for an average of 4 years as compared to an average of 10 years for the non-treated group.
Various laboratory parameters showed changes in favor of the patients treated with trientine HCl. Free and total serum copper, SGOT and serum bilirubin all showed mean increases over baseline in the untreated group which were significantly larger than with the patients treated with trientine HCl. In the 13 patients treated with trientine HCl, previous symptoms and signs relating to d-penicillamine intolerance disappeared in 8 patients, improved in 4 patients, and remained unchanged in one patient. The neurological status in the trientine hydrochloride group was unchanged or improved over baseline, whereas in the untreated group, 6 patients remained unchanged and 6 worsened. Kayser-Fleischer rings improved significantly during trientine HCl treatment.
The clinical outcome of the two groups also differed markedly. Of the 13 patients on therapy with trientine HCl (mean duration of therapy 4.1 years; range 1 to 13 years), all were alive at the data cutoff date, and in the non-treated group (mean years with no therapy 2.7 years; range 3 months to 9 years), 9 of the 12 died of hepatic disease.
Chelating Properties
Preclinical Studies
Studies in animals have shown that trientine HCl has cupriuretic activities in both normal and copper-loaded rats. In general, the effects of trientine HCl on urinary copper excretion are similar to those of equimolar doses of penicillamine, although in one study they were significantly smaller.
Human Studies
Renal clearance studies were carried out with penicillamine and trientine HCl on separate occasions in selected patients treated with penicillamine for at least one year. Six-hour excretion rates of copper were determined off treatment and after a single dose of 500 mg of penicillamine or 1.2 g of trientine HCl. The mean urinary excretion rates of copper were as follows:
No. of
Patients
Single
Dose
Treatment
Basal
Excretion
Rate
(mcg Cu + + /6hr)
Test-dose
Excretion
Rate
(mcg Cu + + /6hr)
6
Trientine, 1.2 g
19
234
4
Penicillamine,
500 mg
17
320
In patients not previously treated with chelating agents, a similar comparison was made:
No. of
Patients
Single
Dose
Treatment
Basal
Excretion
Rate
(mcg Cu + + /6hr)
Test-dose
Excretion
Rate
(mcg Cu + + /6hr)
8
Trientine, 1.2 g
71
1,326
7
Penicillamine,
500 mg
68
1,074
These results demonstrate that trientine HCl is effective as a cupriuretic agent in patients with Wilson s disease although on a molar basis it appears to be less potent or less effective than penicillamine. Evidence from a radio-labelled copper study indicates that the different cupriuretic effect between these two drugs could be due to a difference in selectivity of the drugs for different copper pools within the body.
Pharmacokinetics
Data on the pharmacokinetics of trientine HCl are not available. Dosage adjustment recommendations are based upon clinical use of the drug (see DOSAGE AND ADMINISTRATION).
INDICATIONS AND USAGE
Trientine HCl capsules are indicated in the treatment of patients with Wilson s disease who are intolerant of penicillamine. Clinical experience with trientine HCl capsules 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 HCl capsules and penicillamine cannot be considered interchangeable. Trientine HCl capsules should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.
Unlike penicillamine, trientine HCl capsules are 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 HCl capsules was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.
Trientine HCl capsules are not indicated for treatment of biliary cirrhosis.
CONTRAINDICATIONS
Hypersensitivity to this product.
WARNINGS
Patient experience with trientine HCl is limited (see CLINICAL PHARMACOLOGY). Patients receiving trientine HCl 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
There are no reports of hypersensitivity in patients who have been administered trientine HCl for Wilson s disease. However, there have been reports of asthma, bronchitis and dermatitis occurring after prolonged environmental exposure in workers who use trientine HCl 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 HCl 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 milligram 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 HCl. 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 HCl each inhibit absorption of the other, two hours should elapse between administration of trientine HCl and iron.
It is important that trientine HCl 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
Pregnancy Category C. Trientine HCl 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 HCl 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 HCl is administered to a nursing mother.
Pediatric Use
Controlled studies of the safety and effectiveness of trientine HCl 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 HCl 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 HCl 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 HCl: 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 HCl is not indicated for treatment of biliary cirrhosis, but in one study of 4 patients treated with trientine HCl 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 Amneal Pharmaceuticals at 1-877-835-5472 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 HCl without apparent ill effects. No other data on overdosage are available.
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 HCl capsules is 500 to 750 mg/day for pediatric patients and 750 to 1,250 mg/day for adults given in divided doses two, three or four times daily. This may be increased to a maximum of 2,000 mg/day for adults or 1,500 mg/day for pediatric patients age 12 or under.
The daily dose of trientine HCl 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 HCl 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 HCl capsules, USP, 250 mg, are supplied as hard gelatin caramel colored capsules printed with black ink: TRIENTINE on cap and 250 mg on body. They are available as follows:
Bottles of 100: NDC 69238-1545-1
STORAGE
Keep container tightly closed.
Store refrigerated at 2 to 8 C (36 to 46 F).
Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807
Made in Portugal
Rev. 09-2017-00
Carton Label ⮝
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:43986-008 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (UNII: HC3NX54582) (TRIENTINE - UNII:SJ76Y07H5F) TRIENTINE HYDROCHLORIDE 250 mg
Inactive Ingredients Ingredient Name Strength ISOPROPYL ALCOHOL (UNII: ND2M416302) AMMONIA (UNII: 5138Q19F1X) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) FERROSOFERRIC OXIDE (UNII: XM0M87F357) SHELLAC (UNII: 46N107B71O) BUTYL ALCOHOL (UNII: 8PJ61P6TS3) ALCOHOL (UNII: 3K9958V90M) WATER (UNII: 059QF0KO0R)
Product Characteristics Color brown ((Carmel)) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code TRIENTINE;250mg Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:43986-008-01 1 in 1 CARTON 06/01/2019 1 100 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA210619 06/01/2019
Labeler - Bluepharma - Industria Farmaceutica, S.A. (449909329)
Registrant - Bluepharma - Industria Farmaceutica, S.A. (449909329) Revised: 10/2019 Document Id: 94f98c17-b443-7d8e-e053-2a95a90a7776 Set id: 89a7bc7c-e52f-4dfe-e053-2995a90a3782 Version: 7 Effective Time: 20191015 Bluepharma - Industria Farmaceutica, S.A.
Principal Display Panel ⮝
NDC 0591-4910-01
TrientineHydrochloride
Capsules, USP
250 mg
100 Capsules
Rx only
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0591-4910 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIENTINE HYDROCHLORIDE (UNII: HC3NX54582) (TRIENTINE - UNII:SJ76Y07H5F) TRIENTINE HYDROCHLORIDE 250 mg
Inactive Ingredients Ingredient Name Strength FERROSOFERRIC OXIDE (UNII: XM0M87F357) GELATIN, UNSPECIFIED (UNII: 2G86QN327L) POTASSIUM HYDROXIDE (UNII: WZH3C48M4T) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) SHELLAC (UNII: 46N107B71O) STEARIC ACID (UNII: 4ELV7Z65AP) TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
Product Characteristics Color WHITE (white to off-white) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code A272 Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0591-4910-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 02/08/2018
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA207567 02/08/2018
Labeler - Actavis Pharma, Inc. (119723554) Revised: 5/2017 Document Id: bcbb8581-a9bc-4a51-b2fd-9a059a2e6411 Set id: 89970c97-2535-4856-b155-62d195b5147c Version: 7 Effective Time: 20170531 Actavis Pharma, Inc.
Package Label Principal Display Panel Section ⮝
Trientine Hydrochloirde Capsules USP, 250 mg - Container Label 100's Count
Unvarnished Area consists of: 2D Barcode, Lot Number, Expiry Date and Serial Number.
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:43598-459 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Trientine Hydrochloride (UNII: HC3NX54582) (Trientine - UNII:SJ76Y07H5F) Trientine Hydrochloride 250 mg
Inactive Ingredients Ingredient Name Strength Silicon Dioxide (UNII: ETJ7Z6XBU4) Ferric Oxide Yellow (UNII: EX438O2MRT) Gelatin, Unspecified (UNII: 2G86QN327L) Magnesium Stearate (UNII: 70097M6I30) Polyethylene Glycol, Unspecified (UNII: 3WJQ0SDW1A) Titanium Dioxide (UNII: 15FIX9V2JP) Ferrosoferric Oxide (UNII: XM0M87F357) Potassium Hydroxide (UNII: WZH3C48M4T) Propylene Glycol (UNII: 6DC9Q167V3) Shellac (UNII: 46N107B71O)
Product Characteristics Color YELLOW (yellow opaque) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code RDY;459 Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:43598-459-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 07/03/2019
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA211076 07/03/2019
Labeler - Dr.Reddys Laboratories Inc (802315887)
Establishment Name Address ID/FEI Business Operations Dr. Reddys Laboratories Limited (SEZ UNIT) 860037244 analysis(43598-459) , manufacture(43598-459) Revised: 7/2019 Document Id: 472252a1-4789-c27d-ef58-254bc014519e Set id: fff41159-af99-94bf-4327-8a6a7ee77b36 Version: 3 Effective Time: 20190704 Dr.Reddys Laboratories Inc
Principal Display Panel - 250 Mg Capsule Carton ⮝
NDC 68682-212-10
Rx only
Trientine
Hydrochloride
Capsules250 mg
Oceanside
Pharmaceuticals100Capsules
TRIENTINE HYDROCHLORIDE
trientine hydrochloride capsule
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68682-212 Route of Administration ORAL
Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength trientine hydrochloride (UNII: HC3NX54582) (trientine - UNII:SJ76Y07H5F) trientine hydrochloride 250 mg
Inactive Ingredients Ingredient Name Strength GELATIN, UNSPECIFIED (UNII: 2G86QN327L) Stearic Acid (UNII: 4ELV7Z65AP) Titanium Dioxide (UNII: 15FIX9V2JP)
Product Characteristics Color BROWN (light brown) Score no score Shape CAPSULE Size 19mm Flavor Imprint Code Aton;710;Syprine Contains
Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68682-212-10 1 in 1 CARTON 02/09/2018 1 100 in 1 BOTTLE; Type 0: Not a Combination Product
Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA authorized generic NDA019194 02/09/2018
Labeler - Oceanside Pharmaceutials (832011691)
Establishment Name Address ID/FEI Business Operations Valeant Pharmaceuticals International, Inc. 253292734 MANUFACTURE(68682-212) Revised: 11/2016 Document Id: ac2a4c8c-32ab-4d50-9b12-e8fdbe88d5c3 Set id: 1080f833-a727-4260-b412-519f1612a83c Version: 14 Effective Time: 20161101 Oceanside Pharmaceutials
