threonine 500 MG Oral Capsule

INDICATIONS AND USAGE TRAVASOL is indicated as a source of amino acids for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. TRAVASOL may be used to treat negative nitrogen balance in patients. TRAVASOL is indicated as a source of amino acids for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. TRAVASOL may be used to treat negative nitrogen balance in patients. (1)

DOSAGE AND ADMINISTRATION • Pharmacy Bulk Package. Not for direct intravenous infusion. (2.1) • See full prescribing information for information on preparation, administration, instructions for use, dosing considerations, including the recommended dosage in adults and pediatrics, and dosage modifications in patients with renal impairment. ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 ) • Protect the admixed parenteral nutrition solution from light. ( 2.3 ) 2.1 Important Preparation Information TRAVASOL is supplied as a pharmacy bulk package for admixing only and is not for direct intravenous infusion . Prior to administration, TRAVASOL must be transferred to a separate parenteral nutrition container, diluted and used as an admixture with or without dextrose, electrolytes and/or lipid emulsion. • The key factor in preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients. • Do not remove container from overpouch until ready to use. • Tear protective overpouch across top at slit and remove solution container. Small amounts of moisture may be found on the solution container from water permeating from inside the container. The amount of permeated water is insufficient to affect the solution significantly. If larger amounts of water are found, the container should be checked for tears or leaks. • Inspect TRAVASOL prior to use. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Evaluate the following: o If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. o Check to ensure the solution is clear, colorless or slightly yellow. Discard if the solution is bright yellow or yellowish brown. o Check for minute leaks by squeezing inner container. If leaks are found, discard container. • TRAVASOL is intended for use in the preparation of sterile, intravenous admixtures. Because additives may be incompatible with TRAVASOL, evaluate all additions for compatibility. 2.2 Administration Instructions TRAVASOL is for admixing use only. It is not for direct intravenous infusion. Prior to administration, TRAVASOL must be diluted with other compatible intravenous fluids or used as an admixture with or without dextrose, electrolytes and/or lipid emulsion. • TRAVASOL is to be used only 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. • TRAVASOL is for admixing with dextrose injection and/or lipid emulsions using a parenteral nutrition container. • When TRAVASOL is admixed with dextrose injection and/or lipid emulsion, the choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with greater than 5% dextrose or with osmolarity of 900 mOsm/L or greater must be infused through a central venous catheter [see Warnings and Precautions (5.6) ]. • Use a dedicated line for parenteral nutrition solutions. • Intravenous lipid emulsions can be infused concurrently into the same vein as TRAVASOL-dextrose solutions by a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps. • For administration without lipid emulsion, use a 0.22 micron in-line filter. If lipid emulsion is also administered, use a 1.2 micron in-line filter • To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible containers in series, fully evacuate residual gas in the container prior to administration, do not pressurize the flexible container to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the container runs dry. • If admixed or infused with lipid emulsion, do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer. • Calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium phosphate precipitates [see Warnings and Precautions (5.1) ]. • Prior to infusion, visually inspect the diluted parenteral nutrition solution containing TRAVASOL for particulate matter. The solution should be clear and there should be no precipitates. A slight yellow color does not alter the quality and efficacy of this product. If lipid has been added, ensure the emulsion has not separated. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the mixed emulsion. Discard the admixture if any of the above are observed. 2.3 Preparation Instructions for Admixing Using a Parenteral Nutrition Container • Open by tearing protective overwrap across top at slit and remove solution container. If overpouch has been previously opened or is damaged, discard solution. • If the outlet port protector is damaged, detached, or not present, discard the container. • Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. • Check for minute leaks by squeezing the inner container firmly. If leaks are found, discard solution. • Once the protective foil overwrap has been removed, suspend container from eyelet support. • Remove plastic protector from outlet port at bottom of container. • Attach solution transfer set. Refer to complete directions accompanying set. Note: The closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set which allows measured dispensing of the contents. • Prepare the admixture into the parenteral nutrition container using strict aseptic techniques to avoid microbial contamination. • Do not add the lipid emulsion to the parenteral nutrition container first; destabilization of the lipid emulsion may occur from such an admixture. • TRAVASOL may be mixed with dextrose injection and/or lipid emulsion. The following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic dextrose injections are not mixed with lipid emulsions alone: 1. Transfer dextrose injection to the parental nutrition pooling container. 2. Transfer amino acid injection. 3. Transfer lipid emulsion. • 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. Questions about compatibility may be directed to Baxter. If it is deemed advisable to introduce additives to the parenteral nutrition container, use aseptic technique. • Use gentle agitation during admixing to minimize localized concentration effects; shake containers gently after each addition. • Alternatively, simultaneous transfer to the parenteral nutrition container of TRAVASOL, dextrose injection and lipid emulsion is also permitted. • For admixing using an automated device, refer to Instructions for Use of the applicable device. • The prime destabilizers of emulsions are excessive acidity (such as pH below 5) and inappropriate electrolyte content. Give careful consideration to additions of divalent cations (Ca++ and Mg++), which have been shown to cause emulsion instability. Amino acid solutions exert buffering effects that protect the emulsion. • Inspect the final parenteral nutrition solution containing TRAVASOL to ensure that: o Precipitates have not formed during the mixing or addition of additives. o The emulsion has not separated. Separation of the emulsion ca

WARNINGS AND PRECAUTIONS • Pulmonary Embolism due to Pulmonary Vascular Precipitates: if signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. (5.1) • Hypersensitivity Reactions : monitor for signs and symptoms and discontinue infusion if reactions occur. (5.2) • Risk of Infections, Refeeding Complications, and Hyperglycemia or Hyperosmolar Hyperglycemic State : monitor for signs and symptoms; monitor laboratory parameters. (5.3 , 5.4 , 5.5) • Vein Damage and Thrombosis: solutions with osmolarity of 900 mOsm/L or more must be infused through a central catheter. (2.2 , 5.6) • Hepatobiliary Disorders: monitor liver function parameters and ammonia levels. (5.7) • Aluminum Toxicity: increased risk in patients with renal impairment, including preterm infants. (5.8 , 8.4) • Parenteral Nutrition Associated Liver Disease: increased risk in patients who receive parenteral nutrition for extended periods of time, especially preterm infants; monitor liver function tests, if abnormalities occur consider discontinuation or dosage reduction. (5.9 , 8.4) • Electrolyte Imbalance and Fluid Overload: patients with cardiac insufficiency or renal impairment may require adjustment of fluid, protein and electrolyte content. (5.10 , 8.4) 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, including TRAVASOL. In some cases, fatal outcomes due to pulmonary embolism have occurred. TRAVASOL contains no added phosphorus. Patients, especially those with hypophosphatemia, may require the addition of phosphate. To prevent hypocalcemia, calcium supplementation should always accompany phosphate administration. Excessive addition of calcium and phosphate increases the risk of the formation of calcium phosphate precipitates. Precipitates have been reported even in the absence of phosphate salt in the solution. Precipitation following passage through an in-line filter and suspected in vivo precipitate formation has also been reported. If signs of pulmonary distress occur, stop the infusion and initiate a medical evaluation. In addition to inspection of the solution [see Dosage and Administration (2.1 , 2.2 , 2.3 , 2.4 )] , the infusion set and catheter should also periodically be checked for precipitates. 5.2 Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis have been reported with parenteral nutrition solutions containing TRAVASOL. Stop the infusion immediately and treat patient accordingly if any signs or symptoms of a hypersensitivity reaction develop. Signs or symptoms may include: hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, urticaria, rash, pruritus, erythema, hyperhidrosis, pyrexia, and chills. 5.3 Risk of Infections Patients who require parenteral nutrition are at high risk of infections because the nutritional components of these solutions can support microbial growth. Infection and sepsis may also occur as a result of the use of intravenous catheters to administer parenteral nutrition. The risk of infection is increased in patients with malnutrition-associated immunosuppression, hyperglycemia exacerbated by dextrose infusion, long-term use and poor maintenance of intravenous catheters, or immunosuppressive effects of other concomitant conditions, drugs, or other components of the parenteral formulation (e.g., lipid emulsion). To decrease the risk of infection, ensure aseptic technique in catheter placement and maintenance, as well as aseptic technique in the preparation and administration of the nutritional formula. Monitor for signs and symptoms (including fever and chills) of early infections, including laboratory test results (including leukocytosis and hyperglycemia) and frequent checks of the parenteral access device and insertion site for edema, redness and discharge. 5.4 Refeeding Syndrome Refeeding severely undernourished patients may result in refeeding syndrome, characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. To prevent these complications, monitor severely undernourished patients and slowly increase nutrient intakes. 5.5 Hyperglycemia or Hyperosmolar Hyperglycemic State Administration of parenteral nutrition solutions containing dextrose in patients with diabetes mellitus, impaired glucose tolerance may worsen hyperglycemia. Administration of dextrose at a rate exceeding the patient’s utilization rate may lead to hyperglycemia, coma, and death. Patients with underlying confusion and renal impairment who receive dextrose infusions, may be at greater risk of developing hyperosmolar hyperglycemic state. Monitor blood glucose levels and treat hyperglycemia to maintain optimum levels while administering parenteral nutrition solutions containing dextrose. Insulin may be administered or adjusted to maintain optimal blood glucose levels during administration of parenteral nutrition solutions containing dextrose. 5.6 Vein Damage and Thrombosis TRAVASOL must be diluted and used as an admixture with or without dextrose, electrolytes and/or lipid emulsion. It is not for direct intravenous infusion. Solutions containing more than 5% dextrose or with an osmolarity of 900 mOsm/L or greater must be infused through a central catheter [see Dosage and Administration (2.2) ] . The infusion of hypertonic nutrient injections 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. 5.7 Hepatobiliary Disorders Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive parenteral nutrition, including cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic failure. The etiology of these disorders is thought to be multifactorial and may differ between patients. Increase in blood ammonia levels and hyperammonemia may occur in patients receiving amino acid solutions, including TRAVASOL. In some patients this may indicate hepatic insufficiency or the presence of an inborn error of amino acid metabolism [see Contraindications (4) and Use in Specific Populations (8.4) ] . Monitor liver function parameters and ammonia levels. Patients developing signs of hepatobiliary disorders should be assessed early by a clinician knowledgeable in liver diseases in order to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions. 5.8 Aluminum Toxicity TRAVASOL contains no more than 25 mcg/L of aluminum. However, with prolonged parenteral administration in patients with renal impairment, the aluminum contained in TRAVASOL may reach toxic levels. Preterm infants are at a greater risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with renal impairment, including preterm infants, 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. 5.9 Risk of Parenteral Nutrition Associated Liver Disease Parenteral Nutrition Associated Liver Disease (PNALD) has been reported in patients who receive parenteral nutrition for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis. The exact etiology is unknown and is likely multifactorial. If patients treated with parenteral nutrition solutions containing TRAVASOL develop liver test abnormalities,

CONTRAINDICATIONS The use of TRAVASOL is contraindicated in: • Patients with known hypersensitivity to one or more amino acids [see Warnings and Precautions (5.2) ] . • Patients with inborn errors of amino acid metabolism due to risk of severe metabolic or neurologic complications. • Patients with pulmonary edema or acidosis due to low cardiac output. • Known hypersensitivity to one or more amino acids. (4) • Inborn errors of amino acid metabolism. (4) Patients with pulmonary edema or acidosis due to low cardiac output. (4)

Mechanism of Action TRAVASOL is used as a supplement of nutrition in patients, providing amino acids parenterally. The amino acids provide the structural units that make up proteins and are used to synthesize proteins and other biomolecules or are oxidized to urea and carbon dioxide as a source of energy.