Glutamic Acid

N - Nervous System Small molecule Natural product

Mechanism of Action

— Nutritional support

Indications

Off-label

Sleep Wake Disorders

Contraindications

Source: openFDA

The use of PROSOL 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 ) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

General disorders and administration site conditions (4)

Not Known Discontinue The Infusion · Evaluate The Patient · Inline Filters · Such As Antibiotics

Dosing

Source: openFDA

• 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 PROSOL is supplied as a pharmacy bulk package for admixing only and is not for direct intravenous infusion . Prior to administration, PROSOL 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 PROSOL 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. Amino acid crystals may be present. Crystals will re-dissolve upon dilution during admixture compounding. 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. • PROSOL is intended for use in the preparation of sterile, intravenous admixtures. Because additives may be incompatible with PROSOL, evaluate all additions for compatibility. 2.2 Administration Instructions PROSOL is for admixing use only. It is not for direct intravenous infusion. Prior to administration, PROSOL must be diluted with other compatible intravenous fluids or used as an admixture with or without dextrose, electrolytes and/or lipid emulsion. • PROSOL 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. • PROSOL is for admixing with dextrose injection and/or lipid emulsions using a parenteral nutrition container. • When PROSOL 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 PROSOL -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 pr

Warnings & Precautions

Source: openFDA

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 ) • 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 mOsmol/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 )

Pulmonary Embolism due to Pulmonary Vascular Precipitates Pulmonary va

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. In some cases, fatal outcomes due to pulmonary embolism have occurred. PROSOL 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.

Hypersensitivity Reactions Hypersensitivity reactions including anaphy

Hypersensitivity Reactions Hypersensitivity reactions including anaphylaxis have been reported with parenteral nutrition solutions containing PROSOL. 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.

Risk of Infections Patients who require parenteral nutrition are at hi

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.

Refeeding Syndrome Refeeding severely undernourished patients may resu

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.

Hyperglycemia or Hyperosmolar Hyperglycemic State Administration of pa

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.

Vein Damage and Thrombosis PROSOL must be diluted and used as an admix

Vein Damage and Thrombosis PROSOL 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 mOsmol/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.

Hepatobiliary Disorders Hepatobiliary disorders are known to develop i

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 PROSOL. In some patients, this may indicate hepatic insufficiency or the presence of an inborn error of amino acid metabolism [see Contraindications (4) , 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.

Aluminum Toxicity PROSOL contains no more than 25 mcg/L of aluminum

Aluminum Toxicity PROSOL contains no more than 25 mcg/L of aluminum. However, with prolonged parenteral administration in patients with renal impairment, the aluminum contained in PROSOL 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.

Risk of Parenteral Nutrition Associated Liver Disease Parenteral Nutri

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 PROSOL develop liver test abnormalities, consider discontinuation or dosage reduction.

Electrolyte Imbalance and Fluid Overload Patients with renal impairmen

Electrolyte Imbalance and Fluid Overload Patients with renal impairment, such as pre-renal azotemia, renal obstruction, and protein-losing nephropathy may be at increased risk of electrolyte and fluid volume imbalance. Patients with cardiac insufficiency and pulmonary congestion are susceptible to excess fluid accumulation. Use parenteral nutrition solutions containing PROSOL with caution in patients with cardiac insufficiency or renal impairment. The dosage of parenteral nutrition may require adjustment with specific attention to fluid, protein, and electrolyte content in these patients. Monitor renal function parameters. Patients developing signs of renal impairment should be assessed early by a clinician knowledgeable in renal disease in order to determine the appropriate parenteral nutrition dosage and other treatment options.

Monitoring/Laboratory Tests Monitor fluid and electrolyte status, seru

Monitoring/Laboratory Tests Monitor fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count and coagulation parameters throughout treatment. If electrolyte levels are severely elevated, stop parenteral nutrition containing PROSOL until levels have been corrected.

Chemistry & Properties

Formula	C5H9NO4
Molecular weight	147.13 g/mol
IUPAC name	(2S)-2-aminopentanedioic acid
CAS	56-86-0
PubChem CID	33032
InChIKey	`WHUUTDBJXJRKMK-VKHMYHEASA-N`
logP	-0.74 (XLogP -3.7)
Polar surface area	100.62 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.49
Lipinski violations	0

SMILES

N[C@@H](CCC(=O)O)C(=O)O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.96 h
Volume of distribution	0.222 L/kg
Protein binding	7.4%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—
CYP2D6	Substrate	—

Receptor binding (top 9)

Target	Action	Affinity
Glutamate-Kainate EAA1 (GRIK4)	Binding	pKi 7.7
metabotropic glutamate 8 (GRM8)	Binding	pKi 7.7
metabotropic glutamate 5 (GRM5)	Binding	pKi 7.6
Glutamate-AMPA (GRIA3)	Binding	pKi 6.6
metabotropic glutamate 5a	Binding	pKi 5.8
Metabotropic Glutamate 1a	Binding	pKi 5.8
metabotropic glutamate 4a	Binding	pKi 5.5
metabotropic glutamate 2 (GRM2)	Binding	pKi 5.4
metabotropic glutamate 3 (GRM3)	Binding	pKi 5.4

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MCT1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT(unspecified) (Inhibitor)P-gp (Inhibitor)OCT(unspecified) (Substrate)P-gp (Substrate)

Drug–drug interactions (5, DDInter)

Interacting drug	Severity	Management
Amphetamine	moderate
Benzphetamine	moderate
Dextroamphetamine	moderate
Lisdexamfetamine	moderate
Metamfetamine	moderate

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Olimel N12E	Solution Alanine 10.99 g/1000 ml, Arginine 7.44 g/1000 ml, L-Aspartic acid 2.20 g/1000 ml, Glutamic acid 3.79 g/1000 ml, Glycine 5.26 g/1000 ml, HISTIDINE 4.53 g/1000 ml, isoleucine 3.79 g/1000 ml, Leucine 5.26 g/1000 ml, Lysine acetate 8.43 g/1000 ml, methionine 3.79 g/1000 ml, phenylalanine 5.26 g/1000 ml, proline 4.53 g/1000 ml, Serine 3 g/1000 ml, threonine 3.79 g/1000 ml, Tryptophan 1.26 g/1000 ml, Tyrosine 0.2 g/1000 ml, valine 4.86 g/1000 ml, Sodium Acetate Trihydrate 1.5 g/1000 ml, Sodium Glycerophosphate (Liq 50 %) 3.67 g/1000 ml, Potassium Chloride 2.24 g/1000 ml, Magnesium Chloride Hexahydrate 0.81 g/1000 ml, Calcium Chloride Dihydrated 0.52 g/1000 ml, Glucose Monohydrate 80.67 g/1000 ml, Olive Oil 28 g/1000 ml, Soyabean Oil 7 g/1000 ml	1000 ml	Khoury Drug Store	—
Olimel N12E	Solution Alanine 7.14 g/650 ml, Arginine 4.84 g/650 ml, L-Aspartic acid 1.43 g/650 ml, Glutamic acid 2.46 g/650 ml, Glycine 3.42 g/650 ml, HISTIDINE 2.94 g/650 ml, isoleucine 2.46 g/650 ml, Leucine 3.42 g/650 ml, Lysine acetate 5.48 g/650 ml, methionine 2.46 g/650 ml, phenylalanine 3.42 g/650 ml, proline 2.94 g/650 ml, Serine 1.95 g/650 ml, threonine 2.46 g/650 ml, Tryptophan 0.82 g/650 ml, Tyrosine 0.13 g/650 ml, valine 3.16 g/650 ml, Sodium Acetate Trihydrate 0.97 g/650 ml, Sodium Glycerophosphate (Liq 50 %) 2.39 g/650 ml, Potassium Chloride 1.45 g/650 ml, Magnesium Chloride Hexahydrate 0.53 g/650 ml, Calcium Chloride Dihydrated 0.34 g/650 ml, Glucose Monohydrate 52.43 g/650 ml, Olive Oil 18.2 g/650 ml, Soyabean Oil 4.55 g/650 ml	650 ml	Khoury Drug Store	—
PeriOlimel N4E	Solution Arginine 3.72 g/1500 ml, L-Aspartic acid 1.1 g/1500 ml, Glutamic acid 1.90 g/1500 ml, Glycine 2.63 g/1500 ml, HISTIDINE 2.26 g/1500 ml, isoleucine 1.90 g/1500 ml, Leucine 2.63 g/1500 ml, Lysine acetate 4.21 g/1500 ml, methionine 1.90 g/1500 ml, phenylalanine 2.63 g/1500 ml, proline 2.26 g/1500 ml, Serine 1.5 g/1500 ml, threonine 1.9 g/1500 ml, Tryptophan 0.64 g/1500 ml, Tyrosine 0.1 g/1500 ml, valine 2.43 g/1500 ml, Sodium Acetate Trihydrate 1.73 g/1500 ml, Sodium Glycerophosphate (Liq 50 %) 2.87 g/1500 ml, Potassium Chloride 1.79 g/1500 ml, Magnesium Chloride Hexahydrate 0.67 g/1500 ml, Calcium Chloride Dihydrated 0.440 g/1500 ml, Glucose Monohydrate 123.75 g/1500 ml, Olive Oil 45 g/1500 ml, Soyabean Oil 45 g/1500 ml, Alanine 5.5 g/1500 ml	1500 ml	Khoury Drug Store	—