Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED Tralement (trace elements injection 4*, USP) is a clear, colorless to slightly blue solution supplied as follows: NDC 0517-9305-01 1 mL single-dose vial NDC 0517-9305-25 Packaged in trays containing 25 vials per tray *Each mL of Tralement contains zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg. Vial closure is not made with natural rubber latex. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Store admixed solution at 2ºC to 8ºC (36ºF to 46ºF) [see Dosage and Administration ( 2.3 )].; PRINCIPAL DISPLAY PANEL - Container Label (1 mL) 0517-9305-01 Rx Only Tralement ® (trace elements injection 4*, USP) *Each mL provides: zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg Contains no more than 6,000 mcg/L of aluminum. For intravenous infusion after admixing For use in adult and pediatric patients weighing at least 10 kg 1 mL Single-Dose Vial Discard Unused Portion 1ml via label tralement; PRINCIPAL DISPLAY PANEL - Carton Labeling (1 mL) 0517- 9305 -25 Rx Only Tralement ® (trace elements injection 4*, USP) *Each mL provides: zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg For intravenous infusion after admixing For use in adult and pediatric patients weighing at least 10 kg 25 x 1 mL Single-Dose Vials Discard Unused Portion 1ml carton tralement
- 16 HOW SUPPLIED Tralement (trace elements injection 4*, USP) is a clear, colorless to slightly blue solution supplied as follows: NDC 0517-9305-01 1 mL single-dose vial NDC 0517-9305-25 Packaged in trays containing 25 vials per tray *Each mL of Tralement contains zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg. Vial closure is not made with natural rubber latex. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Store admixed solution at 2ºC to 8ºC (36ºF to 46ºF) [see Dosage and Administration ( 2.3 )].
- PRINCIPAL DISPLAY PANEL - Container Label (1 mL) 0517-9305-01 Rx Only Tralement ® (trace elements injection 4*, USP) *Each mL provides: zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg Contains no more than 6,000 mcg/L of aluminum. For intravenous infusion after admixing For use in adult and pediatric patients weighing at least 10 kg 1 mL Single-Dose Vial Discard Unused Portion 1ml via label tralement
- PRINCIPAL DISPLAY PANEL - Carton Labeling (1 mL) 0517- 9305 -25 Rx Only Tralement ® (trace elements injection 4*, USP) *Each mL provides: zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg For intravenous infusion after admixing For use in adult and pediatric patients weighing at least 10 kg 25 x 1 mL Single-Dose Vials Discard Unused Portion 1ml carton tralement
Overview
Tralement ® (trace elements injection 4*, USP) is a sterile, non-pyrogenic, clear, and colorless to slightly blue solution, intended for use as a combination of four trace elements and an additive to intravenous solutions for parenteral nutrition. It contains no preservative. Each single-dose vial contains 1 mL and each multiple-dose vial contains 10 mL. *Each mL contains zinc 3 mg (equivalent to zinc sulfate 7.41 mg), copper 0.3 mg (equivalent to cupric sulfate 0.75 mg), manganese 55 mcg (equivalent to manganese sulfate 151 mcg), selenium 60 mcg (equivalent to selenious acid 98 mcg), and water for injection. Sulfuric acid may be added to adjust pH between 1.5 and 3.5. Zinc sulfate exists as a heptahydrate. The structural formula is: Molecular formula: ZnSO 4 • 7H 2 O. Molecular weight: 287.54 g/mol. Cupric sulfate exists as a pentahydrate. The structural formula is: Molecular formula: CuSO 4 • 5H 2 O. Molecular weight: 249.69 g/mol. Manganese sulfate exists as a monohydrate. The structural formula is: Molecular formula: MnSO 4 • H 2 O. Molecular weight: 169.02 g/mol. The structural formula of selenious acid is: Molecular formula: H 2 SeO 3 . Molecular weight: 128.97 g/mol. Tralement contains no more than 6,000 mcg/L of aluminum. Zinc Sulfate Structural Formula Cupric Sulfate Structural Formula Manganese Structural Formula Selenious Acid Structural Formula
Indications & Usage
Tralement ® is indicated in adult and pediatric patients weighing at least 10 kg as a source of zinc, copper, manganese, and selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Tralement is a combination of trace elements (zinc sulfate, cupric sulfate, manganese sulfate and selenious acid) indicated in adult and pediatric patients weighing at least 10 kg as a source of zinc, copper, manganese, and selenium for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. ( 1 )
Dosage & Administration
Single-dose vial amd multiple-dose vial . Not for direct intravenous infusion. ( 2.1 ) See full prescribing information for information on preparation, administration and general dosing considerations. ( 2.1 , 2.2 , 2.3 , 2.4) Recommended Dosage Each mL of Tralement provides zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg. ( 2.5 ) Adults and Pediatric Patients Weighing at Least 50 kg : The recommended dosage of Tralement is 1 mL per day added to parenteral nutrition. Tralement is not recommended for patients who may require a lower dosage of one or more of the individual trace elements. ( 2.5 ) Pediatric Patients Weighing 10 kg to 49 kg : The recommended dosage of Tralement based on body weight is 0.2 mL to 0.8 mL per day added to parenteral nutrition. Tralement does not provide the recommended daily dosage of zinc (in heavier patients in some weight bands), copper or selenium. Additional supplementation using single trace element products may be needed for these patients. For complete dosing information see table in the full prescribing information. ( 2.4 , 2.5 ) Monitor trace element concentrations in blood during long-term administration of parenteral nutrition. ( 2.5 ) 2.1 Important Administration Information Tralement is supplied as a single-dose vial and multiple-dose vial for admixture use only. It is not for direct intravenous infusion . Prior to administration, Tralement must be transferred to a separate parenteral nutrition container and used as an admixture in parenteral nutrition solution. The final parenteral nutrition solution is for intravenous infusion into a central or peripheral vein. The choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [ see Warnings and Precautions ( 5.2 )] . 2.2 Preparation and Administration Instructions Tralement is not for direct intravenous infusion. Prior to administration, Tralement must be prepared and used as an admixture in parenteral nutrition solution. Add Tralement to the parenteral nutrition solution in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). The key factor in the preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients. Inspect the parenteral nutrition solution containing Tralement for particulate matter before admixing, after admixing, and prior to administration. 2.3 Preparation Instructions for Admixing Using a Parenteral Nutrition Container Inspect Tralement single-dose vial and multiple-dose vial for particulate matter. Transfer Tralement to the parenteral nutrition container after the admixture of amino acids, dextrose, lipid emulsion (if added), and electrolytes solutions is prepared. Because additives may be incompatible, evaluate all additions to the parenteral nutrition container for compatibility and stability of the resulting preparation. Consult with pharmacist, if available. For introducing additives to the parenteral nutrition container, use aseptic technique. An interaction may occur between cupric ion and ascorbic acid; therefore, multivitamin additives should be added to the admixed parenteral nutrition solution shortly before infusion. Inspect the final parenteral nutrition solution containing Tralement to ensure that: o Precipitates have not formed during mixing or addition on additives. o The emulsion has not separated, if lipid emulsion has been added. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. o Discard if any precipitates are observed. Stability and Storage Single-dose vial. Discard unused portion. Multiple-dose vial: May puncture up to 20 times. Discard any unused portion after 28 days. Use parenteral nutrition solutions containing Tralement promptly after mixing. Any storage of the admixture should be under refrigeration from 2ºC to 8ºC (36ºF to 46ºF) and limited to a period of no longer than 9 days. After removal from refrigeration, use promptly and complete the infusion within 24 hours. Discard any remaining admixture. Protect the parenteral nutrition solution from light. 2.4 Overview of Dosing Prior to administration of parenteral nutrition solution containing Tralement, correct severe fluid, electrolyte, and acid-base disorders. The dosage of the final parenteral nutrition solution containing Tralement must be based on the concentrations of all components in the solution, the patient’s clinical condition, nutritional requirements, and the contribution of oral or enteral intake. For pediatric patients weighing 10 to 49 kg, Tralement does not provide the recommended daily dosage of zinc (in heavier patients in some weight bands), copper or selenium. Additional supplementation using single trace element products may be needed for these patients [ see Dosage and Administration (2.5)]. Monitor fluid and electrolyte status during treatment use of Tralement and adjust the parenteral nutrition solution as needed 2.5 Recommended Dosage and Monitoring in Adult and Pediatric Patients Tralement is a fixed-combination product. Each mL of Tralement provides zinc 3 mg, copper 0.3 mg, manganese 55 mcg, and selenium 60 mcg. Tralement is recommended only for patients who require supplementation with all four of the individual trace elements (i.e., zinc, copper, manganese and selenium). Adults and Pediatric Patients Weighing at least 50 kg : The recommended dosage of Tralement is 1 mL per day added to parenteral nutrition (zinc 3 mg/copper 0.3 mg/manganese 55 mcg/selenium 60 mcg). Tralement is not recommended for those patients who may require a lower dosage of one or more of the individual trace elements. Pediatric Patients Weighing 10 kg to 49 kg : The recommended dosage of Tralement by volume to be added to parenteral nutrition is based on body weight and ranges from 0.2 mL to 0.8 mL per day as shown in Table 1. Body Weight Recommended Weight-Based Dosage of Tralement in Volume Amount of Trace Element Provided by the Corresponding Tralement Volume Zinc Copper Manganese Selenium 10 kg to 19 kg 0.2 mL 600 mcg 60 mcg 11 mcg 12 mcg 20 kg to 29 kg 0.4 mL 1,200 mcg 120 mcg 22 mcg 24 mcg 30 kg to 39 kg 0.6 mL 1,800 mcg 180 mcg 33 mcg 36 mcg 40 kg to 49 kg 0 .8 mL 2,400 mcg 240 mcg 44 mcg 48 mcg Use Additional Supplementation with Tralement For pediatric patients weighing 10 kg to 49 kg, additional zinc (in heavier patients in some weight bands), copper and selenium may be needed to meet the recommended daily dosage of these trace elements, shown below. To determine the additional amount of supplementation that is needed, compare the calculated daily recommended dosage based on the body weight of the patient to the amount of each trace element provided by Tralement (Table 1) and other oral or enteral nutrition sources. Zinc: 50 mcg/kg/day (up to 3,000 mcg/day) Copper: 20 mcg/kg/day (up to 300 mcg/day) Selenium: 2 mcg/kg/day (up to 60 mcg/day) Do not supplement Tralement with additional manganese. Accumulation of manganese in the brain can occur with long-term administration with higher than the recommended dosage of 1 mcg/kg/day (up to 55 mcg/day) [ see Warnings and Precautions (]. Monitoring Monitor serum zinc, copper, and selenium concentrations and manganese whole blood concentrations during long-term administration of parenteral nutrition. Trace elements concentrations may vary depending on the assay used and the laboratory reference range. The collection, processing, and storage of the blood samples should be performed according to the laboratory’s sample requirements for analysis. o Zinc : In serum, the reported concentration range in healthy adults is 60 to 140 mcg/dL. Zinc concentrations in hemolyzed samples may be falsely elevated due to release of zinc from erythrocytes. o Copper : In serum, the reported concentration range in healthy adults is 70 to 175 mcg/dL; consider obtaining concentrations of ceruloplasmin along with serum copper. o Manganese : In whole blood, the reported concentration range in healthy adults is 4 to 16 mcg/L. o Selenium : In serum, the reported concentration range in healthy adults is 7 to 19 mcg/dL.
Warnings & Precautions
Pulmonary Embolism due to Pulmonary Vascular Precipitates : If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. (5.1) Vein Damage and Thrombosis : Solutions with osmolarity of 900 mOsmol/L or more must be infused through a central catheter. ( 2.1 , 5.2 ) Neurologic Toxicity with Manganese : Monitor for clinical signs and symptoms of neurotoxicity, whole blood manganese concentrations and liver function tests in patients receiving long-term Tralement. Discontinue Tralement and consider brain magnetic resonance imaging (MRI) if toxicity suspected. ( 5. 3) Hepatic Accumulation of Copper and Manganese : Assess for development of hepatic or biliary dysfunction. Monitor concentrations of copper and manganese in patients with cholestasis, biliary dysfunction or cirrhosis receiving Tralement long-term. ( 5.4 ) Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm infants. ( 5.5 , 8.4 ) Monitoring and Laboratory Tests : Monitor blood zinc, copper, manganese, and selenium concentrations, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count and coagulation parameters. ( 5.6 , 2.4 ) Hypersensitivity Reactions with Zinc and Copper : If reactions occur, discontinue Tralement and initiate appropriate medical treatment. ( 5.7) To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. The cause of precipitate formation has not been determined in all cases; however, in some fatal cases, pulmonary emboli occurred as a result of calcium phosphate precipitates. Precipitation has occurred following passage through an in-line filter; in vivo precipitate formation may also have occurred. If signs of pulmonary distress occur, stop the parenteral nutrition infusion and initiate a medical evaluation. In addition to inspection of the solution [ see Dosage and Administration (2.2, 2.3)] , the infusion set, and catheter should also periodically be checked for precipitates. 5.2 Vein Damage and Thrombosis Tralement must be prepared and used as an admixture in parenteral nutrition solution. It is not for direct intravenous infusion. In addition, consider the osmolarity of the final parenteral nutrition solution in determining peripheral versus central administration. Solution with an osmolarity of 900 mOsmol/L or greater must be infused through a central catheter [ see Dosage and Administration ( 2.1 )]. The infusion of hypertonic nutrient solution into a peripheral vein may result in vein irritation, vein damage, and/or thrombosis. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or a palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops. 5.3 Neurologic Toxicity with Manganese Manganese accumulation in the basal ganglia has been reported in adult and pediatric patients on long-term parenteral nutrition receiving manganese at higher than recommended dosages and in association with cholestatic liver disease. Some adult patients with brain MRI findings reportedly experienced neuropsychiatric symptoms, including changes in mood or memory, seizures and/or parkinsonian-like tremors, dysarthria, mask-face, and halting gait. Some pediatric patients experienced dystonic movements or seizures. Brain MRI findings and clinical symptoms have also been observed in patients who received manganese at or below the recommended dosage and with normal blood manganese concentrations. Regression of symptoms and MRI findings have occurred over weeks to months following discontinuation of manganese in most patients but have not always completely resolved. Monitor patients receiving long-term parenteral nutrition solutions containing Tralement for neurologic signs and symptoms and routinely monitor whole blood manganese concentrations and liver function tests. In case of suspected manganese toxicity or new neuro-psychiatric manifestations, temporarily discontinue Tralement, check manganese whole blood concentrations, and consider brain MRI evaluation. Monitor patients receiving Tralement for cholestasis or other biliary liver disease. Consider individual trace element products as an alternative to Tralement in patients with hepatic and/or biliary dysfunction [ see Warnings and Precautions ( 5. 4) ]. 5.4 Hepatic Accumulation of Copper and Manganese Copper is primarily eliminated in the bile and excretion is decreased in patients with cholestasis and/or cirrhosis. Hepatic accumulation of copper and manganese have been reported in autopsies of patients receiving long-term parenteral nutrition containing copper and manganese at dosages higher than recommended. Patients receiving parenteral nutrition with cholestasis and/or cirrhosis are at increased risk of manganese brain deposition and neurotoxicity [see Warnings and Precautions ( 5.3 ) ]. Administration of copper to patients with cholestasis, and/or cirrhosis may cause hepatic accumulation of copper. Administration of copper to patients with Wilson disease, an inborn error of copper metabolism with defect in hepatocellular copper transport, may cause both increased hepatic accumulation of copper and aggravation of the underlying hepatocellular degeneration. For patients with cholestasis, biliary dysfunction, or cirrhosis, monitor hepatic and biliary function during long-term administration of Tralement. If a patient develops signs or symptoms of hepatic or biliary dysfunction during the use of Tralement, obtain serum concentrations of copper and ceruloplasmin as well as manganese whole blood concentrations. Consider using individual trace element products in patients with hepatic and/or biliary dysfunction [ see Use in Specific Populations ( 8.6) ] . 5.5 Aluminum Toxicity Tralement contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Preterm infants, including preterm neonates, are particularly at risk because their kidneys are immature and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including preterm infants and premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration or lower daily amounts. Exposure to aluminum from Tralement is no more than 0.1 mcg/kg/day. When prescribing Tralement for use in parenteral nutrition containing other small volume parenteral products, the total daily patient exposure to aluminum from the admixture should be considered and maintained at no more than 5 mcg/kg/day [see Use in Specific Populations ( 8.4 )] . 5.6 Monitoring and Laboratory Tests Monitor blood zinc, copper, manganese, and selenium concentrations, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count, and coagulation parameters during use of parenteral nutrition containing Tralement [ see Dosage and Administration ( 2.4 ) ]. 5.7 Hypersensitivity Reactions with Zinc and Copper Hypersensitivity reactions to subcutaneously administered zinc-containing insulin products and copper-containing intrauterine devices (IUD) were identified in postmarketing case reports. If hypersensitivity reactions occur in patients receiving Tralement in parenteral nutrition, discontinue Tralement, and initiate appropriate medical treatment [ see Contraindications ( 4 )] . Zinc For patients prescribed zinc-containing insulin products, reported reactions included injection site induration, erythema, pruritus, papular rash, generalized urticaria, facial swelling, and dyspnea. Patients did not manifest symptoms after changing to zinc-free insulin or another insulin product with a reduced amount of zinc. In some cases, allergy testing confirmed the allergy to the zinc component of the insulin product. Copper For women with copper IUD implantation, reported reactions included diffuse eczematous dermatitis, maculopapular skin eruption, urticaria, and angioedema of the eyelids, face, and labia weeks or months after IUD insertion. In most cases, the patch test for copper was positive, and the adverse reactions resolved after IUD removal.
Contraindications
Tralement is contraindicated in patients with hypersensitivity to zinc or copper [ see Warnings and Precautions ( 5.7 )]. Hypersensitivity to zinc or copper ( 4, 5.7 )
Adverse Reactions
The following adverse reactions were identified in clinical studies or post-marketing reports. Given that some of these reactions were 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. Adverse reactions with other components of parenteral nutrition solutions : • Pulmonary embolism due to pulmonary vascular precipitates [ see Warnings and Precautions ( 5. 1 )] • Vein damage and thrombosis [ see Warnings and Precautions ( 5.2 )] • Aluminum toxicity [see Warnings and Precautions ( 5.5 )] Adverse reactions with the use of trace elements administered parenterally or by other routes of administration : • Neurologic toxicity with manganese [see Warnings and Precautions ( 5.3 )] • Hepatic accumulation of copper and manganese [see Warnings and Precautions ( 5.4 )] • Hypersensitivity reactions with zinc and copper [ see Warnings and Precautions ( 5.7) ] No adverse reactions related to zinc, copper, selenium, or manganese have been reported in patients receiving intravenously administered parenteral solutions containing these trace elements within the recommended dosage range. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088, or www.fda.gov/medwatch.
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