Trientine Tetrahydrochloride
FDA Drug Information • Also known as: Cuvrior
- Brand Names
- Cuvrior
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION CUVRIOR contains trientine tetrahydrochloride which is a salt of trientine, a copper chelator. The structural formula of trientine tetrahydrochloride is: Molecular Formula C 6 H 22 Cl 4 N 4 Molecular Weight 292.08 g mol -1 CUVRIOR (trientine tetrahydrochloride) tablets are for oral administration and contain 300 mg of trientine tetrahydrochloride (equivalent to 150 mg trientine). Tablets include the following inactive ingredients: colloidal silicon dioxide, glyceryl dibehenate, and mannitol. The film coating comprises ferric oxide yellow, glyceryl monocaprylocaprate (Type I), polyvinyl alcohol, purified talc, sodium lauryl sulfate, and titanium dioxide. Chemical Structure
What Is Trientine Tetrahydrochloride Used For?
1 INDICATIONS AND USAGE CUVRIOR is indicated for the treatment of adult patients with stable Wilson's disease who are de-coppered and tolerant to penicillamine. CUVRIOR is a copper chelator indicated for the treatment of adult patients with stable Wilson's disease who are de-coppered and tolerant to penicillamine. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Recommended Dosage and Administration Starting total daily dosage of CUVRIOR in adults is 300 mg up to 3,000 mg orally in divided doses (2 times daily). See full prescribing information for recommended conversion table when switching from penicillamine to CUVRIOR. ( 2.1 ) Total daily dosage of CUVRIOR should not exceed 3,000 mg. ( 2.1 ) If the number of CUVRIOR tablets prescribed per day cannot be equally divided among doses, then divide total daily dosage such that the higher number of tablets is taken with the first daily dose. ( 2.1 ) Take CUVRIOR on an empty stomach. ( 2.2 ) Swallow tablets without crushing, chewing, or dissolving tablets. ( 2.2 ) Switching from Other Trientine Products CUVRIOR is not substitutable on a milligram-per-milligram basis with other trientine products. ( 2.3 ) See full prescribing information for additional information on switching from other trientine products. ( 2.3 ) Clinical Monitoring and Laboratory Monitoring of Copper Adjust CUVRIOR dosage according to clinical assessment and laboratory monitoring of copper. ( 2.4 ) See full prescribing information for monitoring recommendations. ( 2.4 ) 2.1 Recommended Dosage and Administration The recommended starting total daily dosage of CUVRIOR in adult patients is 300 mg up to 3,000 mg taken orally in divided doses (two times daily). Table 1 provides the recommended starting total daily dosage of CUVRIOR in adult patients switching from penicillamine to CUVRIOR [see Clinical Studies (14) ] . Discontinue penicillamine before starting CUVRIOR. Table 1: Recommended Starting Total Daily Dosage of CUVRIOR when Switching from Penicillamine to CUVRIOR Penicillamine Total Daily Dosage CUVRIOR Starting Total Daily Dosage 125 mg 300 mg 250 mg 600 mg 375 mg 900 mg 500 mg 900 mg 625 mg 1,200 mg 750 mg 1,500 mg 875 mg 1,800 mg 1,000 mg 2,100 mg 1,125 mg 2,400 mg 1,250 mg 2,400 mg 1,375 mg 2,700 mg 1,500 mg or greater 3,000 mg Adjust the total daily dosage of CUVRIOR according to clinical assessment and laboratory monitoring of copper [see Dosage and Administration (2.4) ] . The total daily dosage of CUVRIOR should not exceed 3,000 mg. If the number of CUVRIOR tablets prescribed per day cannot be equally divided among doses, then divide the total daily dosage such that the higher number of tablets is administered with the first daily dose. Table 2 provides the recommended approach to administration of CUVRIOR tablets to achieve the total daily dosage. Table 2: Recommended Administration Schedule of CUVRIOR Tablets to Achieve Total Daily Dosage CUVRIOR Number of CUVRIOR Tablets to Administer Total Daily Dosage Morning Evening 300 mg 1 0 600 mg 1 1 900 mg 2 1 1,200 mg 2 2 1,500 mg 3 2 1,800 mg 3 3 2,100 mg 4 3 2,400 mg 4 4 2,700 mg 5 4 3,000 mg 5 5 2.2 Important Administration Instructions Discontinue penicillamine before starting CUVRIOR [see Dosage and Administration (2.1) ] . Administer CUVRIOR on an empty stomach, at least 1 hour before meals or 2...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Potential for Worsening of Clinical Symptoms at Initiation of Therapy [see Warnings and Precautions (5.1) ] Copper Deficiency [see Warnings and Precautions (5.2) ] Iron Deficiency [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] Most common adverse reactions (>5%) are abdominal pain, change of bowel habits, rash, alopecia, and mood swings. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orphalan at 1-800-961-8320 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Common Adverse Reactions Table 3 presents common adverse reactions over a 24-week period from Trial 1, a prospective, randomized, multi-center study that was conducted in adult patients with Wilson's disease who were de-coppered and tolerant to penicillamine [see Clinical Studies (14) ] . Patients were either switched to receive CUVRIOR (N=26) or continued to receive penicillamine (N=27). Table 3: Common Adverse Reactions Adverse reactions that occurred in >5% of CUVRIOR-treated patients and greater than in patients who continued to receive penicillamine. from a Clinical Study of CUVRIOR in Adult Patients with Wilson's Disease (Trial 1) Adverse Reaction CUVRIOR (N=26) n (%) Penicillamine (N=27) n (%) Abdominal pain Abdominal pain is composed of several similar terms 5 (19%) 1 (4%) Change of bowel habits Includes constipation, abnormal feces, soft feces 4 (15%) 0 Rash Rash is composed of several similar terms 3 (12%) 0 Alopecia 2 (8%) 1 (4%) Mood swings 2 (8%) 0 Other Adverse Reactions In Trial 1, anemia developed in 4% (1/26) of CUVRIOR-treated patients and in no patients who continued to receive penicillamine. In addition, the following adverse reactions have been reported in clinical studies of patients with Wilson's disease who were on therapy with trientine hydrochloride: Metabolism and Nutrition Disorders : Iron deficiency Musculoskeletal and Connective Tissue Disorders : Systemic lupus erythematosus 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of trientine hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Gastrointestinal Disorders : Colitis Musculoskeletal and Connective Tissue Disorders : Muscle spasms, Rhabdomyolysis Nervous System Disorders: Dystonia, Myasthenia gravis
Drug Interactions
7 DRUG INTERACTIONS Mineral Supplements (e.g. iron, zinc, calcium, magnesium): Avoid concomitant use. If concomitant use is unavoidable ( 2.2 , 7.1 ): Iron : Take CUVRIOR at least 2 hours before or 2 hours after iron. Other Mineral Supplements : Take CUVRIOR at least 1 hour before or 2 hours after other mineral supplements. Other Drugs for Oral Administration : Take CUVRIOR at least 1 hour apart from any other oral drug. ( 2.2 , 7.1 ) 7.1 Mineral Supplements and Other Oral Drugs CUVRIOR has the potential to chelate non-copper cations in mineral supplements and other oral drugs, and could be rendered ineffective prior to systemic absorption. Mineral Supplements Avoid concomitant use of mineral supplements such as iron, zinc, calcium, or magnesium with CUVRIOR because they may reduce the absorption of CUVRIOR. However, if iron deficiency develops [see Warnings and Precautions (5.3) ], iron supplementation may be given in short courses, but because iron and CUVRIOR each inhibit absorption of the other, administer CUVRIOR at least 2 hours before or 2 hours after administration of an iron supplement [see Dosage and Administration (2.2) ]. If concomitant use of other mineral supplements is unavoidable, administer CUVRIOR at least 1 hour before or 2 hours after administration of other mineral supplements. Other Drugs for Oral Administration Administer CUVRIOR at least 1 hour apart from any other oral drug.
Contraindications
4 CONTRAINDICATIONS CUVRIOR is contraindicated in patients with hypersensitivity to trientine or to any of the excipients in CUVRIOR [see Warnings and Precautions (5.4) ] . Hypersensitivity to trientine or to any of the excipients in CUVRIOR. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Available data from published literature and postmarketing experience over several decades with use of trientine for the treatment of Wilson's disease have not identified any drug-associated risks for major birth defects, miscarriages, or other adverse maternal or fetal outcomes. Untreated Wilson's disease may result in worsening disease symptoms during pregnancy and increase the risk of miscarriages in some symptomatic patients (see Clinical Considerations ) . In animal reproduction studies, oral administration of trientine in rats during organogenesis resulted in increased embryo-fetal loss at a dose lower than the maximum recommended dose and produced fetal abnormalities at 2.7 times the maximum recommended dose. Copper supplementation in pregnant rats produced a marked reduction in trientine-induced fetal abnormalities. Oral administration of trientine dihydrochloride to pregnant mice during organogenesis increased the percentage of mice with total embryo-fetal loss at approximately 4.3 times the maximum recommended dose and produced fetal abnormalities at approximately 1.1 times the maximum recommended dose. The mechanism of embryo-fetal harm (e.g., copper depletion) was not determined in the mouse study [see Warnings and Precautions (5.2) and Data ]. Monitor copper levels throughout pregnancy and use the minimum effective dosage of CUVRIOR throughout pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Untreated Wilson's disease or discontinuation of treatment during pregnancy may result in worsening neurological and hepatic...
Overdosage
10 OVERDOSAGE Occasional cases of trientine overdose have been reported. A large overdose of 60 g of trientine hydrochloride (equivalent to 80 g CUVRIOR) resulted in nausea, vomiting, dizziness, mild acute kidney injury, mild hypophosphatemia, low serum zinc, and low serum copper. The patient recovered following intravenous hydration and supportive measures. There is no antidote for trientine acute overdose. Chronic use of trientine hydrochloride at dosages above the maximum recommended dosage has resulted in sideroblastic anemia.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING CUVRIOR tablets, 300 mg of trientine tetrahydrochloride, are oblong, yellow coated, functionally scored, and imprinted with OL75 on each side. Each large carton (NDC 81802-001-72) contains nine child-resistant small cartons (NDC 81802-001-08), each containing a blister pack of 8 tablets (a total of 72 tablets in the large carton). The fewest number of tablets that can be dispensed is 8 tablets in a small carton. Do not remove tablets from the blister pack until the time of dosing. Store at a controlled room temperature of 20°C to 25°C (68°F to 77°F); excursions between 15°C and 30°C (59°F and 86°F) are permitted [see USP Controlled Room Temperature] .
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.