Cupric sulfate, manganese sulfate, selenious acid, and zinc sulfate

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.

Consider using individual trace element products in patients with hepatic and/or biliary dysfunction [ see Use in Specific Populations ] . 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] . 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 ]. 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.

Hepatic Impairment Copper is primarily excreted in the bile. Excretion is decreased in patients with cholestasis and/or cirrhosis. Manganese is found, and presumed to be excreted, in bile [see Clinical Pharmacology]. Hepatic accumulation of copper and manganese have been reported with long-term administration in parenteral nutrition at dosages higher than recommended [see Warnings and Precautions ].

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 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.

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] .

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.

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.

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]. Monitor fluid and electrolyte status during treatment use of Tralement and adjust the parenteral nutrition solution as needed