Magnesium Chloride

CLINIMIX E (Amino Acids with Electrolytes in Dextrose Injection) products are indicated as a source of amino acids and carbohydrate calories in clinical conditions where enteral nutritional supply is or is expected to be insufficient or impossible in order to offset or prevent nitrogen loss or negative nitrogen balance.

1 Pediatrics Pediatrics (<18 years of age): There have been no studies performed by Baxter Corporation in the pediatric population. 3 Pediatrics regarding monitoring for hyperammonemia in pediatric patients. 2 Geriatrics Geriatrics (> 65 years of age): In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

1 Dosing Considerations  CLINIMIX E products contain dextrose and amino acids (Blend C) (see Table 1). 4 Administration). 4 Administration) prior to use (see Table 1 for the contents of the products in the resulting Admixed solution).

 Do not infuse the solution packaged in a chamber without prior mixing. 4 Administration when including electrolytes and lipid emulsion.  Do not add any additives including electrolytes and lipid emulsion until the solutions in the two chambers are thoroughly mixed to reduce the risk of instability of the resulting solution and formation of precipitates which may result in serious clinical outcomes (see 2 CONTRAINDICATIONS, Respiratory subsection of 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

Additives must be added before lipid component to facilitate visual inspection for incompatibility.  Since CLINIMIX E products contain phosphate ions (Table 1), addition of certain cations, especially calcium ions, into the Admixed solution may result in precipitation of phosphate salts which may result in serious clinical outcomes (see 2 CONTRAINDICATIONS, Respiratory subsection of 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

 Discard any solution where precipitates, particulate matter, cloudiness, discoloration and/or other unusual appearance are observed. 4 Administration).  During infusion, the infused solution, infusion set and catheter should periodically be checked for precipitates.

If precipitates (particulate matter) are observed, the infusion must be stopped immediately and medical evaluation initiated.  Adequate measures should be taken to prevent hyperkalemia when CLINIMIX E products are used due to the high potassium concentration of the products (30 mmol/L, see Table 1)  If electrolytes are to be added to CLINIMIX E products, the type and the amount of electrolytes should be dictated by the status of electrolyte balance, disease condition and related vital organ function of the patient.

 For single use only.

Product Monograph Master Template Template Date:

September 2020 CLINIMIX E (Blend C) Page 6 of 31  When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure after admixture through administration.  It is recommended that after opening the bag, the contents should be used immediately, and should not be stored for a subsequent infusion.

Table 1 - The Contents of the Admixed Solution* of CLINIMIX E Amino Acids (Blend C) with Electrolytes in Dextrose Injection. 4 Dextrose (g/L) 100 166 Energy: Total energy from amino acids and dextrose approx. (Kcal/L) 540 764 Energy from dextrose approx.

5 / 5 Phosphate (mmol/L) / (mEq/L) 15 / 30 15 / 30 Chloride (mmol/L) 35 35 Acetate (mmol/L) 75 75 Osmolarity approx. , amino acids and dextrose) should be based on individual nutritional requirements and patient tolerance. The total daily dose of these solutions depends on the patient’s metabolic requirement and clinical response.

The determination of nitrogen balance and accurate daily body weights (corrected for fluid balance), are probably the best means of assessing individual nitrogen requirements. 8 g/kg of body weight for adults. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially.

5 g/kg of body weight for adults and 2 to 3 g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate will be necessary to promote adequate patient response to therapy.

The severity of the illness being treated is the primary consideration in determining proper dose level. Higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation. Care should be exercised to ensure the maintenance of proper levels of serum potassium.

It may be necessary to add additional quantities of this electrolyte to the solution in order to meet the patient’s potassium intake needs. Potassium requirements in a parenteral nutrition (PN) formulation for generally healthy people with normal losses are 1-2 mmol/kg/day, but should be customized to meet individual patient needs.

CLINIMIX E product inherently contains potassium 30 mmol/L, and this should be taken into account prior to any supplemental potassium additions. g. renal failure), acceptable total daily administration volumes are dependent upon the fluid balance requirements of the patient.

Extreme care should be given to prevent fluctuations of blood osmolarity and serum electrolyte concentrations. Frequent and careful monitoring is mandatory when fluid restricted patients […]

). Additives must be added before lipid component to facilitate visual inspection for incompatibility.  Since CLINIMIX E products contain phosphate ions (Table 1), addition of certain cations, especially calcium ions, into the Admixed solution may result in precipitation of phosphate salts which may result in serious clinical outcomes (see 2 CONTRAINDICATIONS, Respiratory subsection of 7 WARNINGS AND PRECAUTIONS and 8 ADVERSE REACTIONS).

 Discard any solution where precipitates, particulate matter, cloudiness, discoloration and/or other unusual appearance are observed. 4 Administration).  During infusion, the infused solution, infusion set and catheter should periodically be checked for precipitates.

If precipitates (particulate matter) are observed, the infusion must be stopped immediately and medical evaluation initiated.  Adequate measures should be taken to prevent hyperkalemia when CLINIMIX E products are used due to the high potassium concentration of the products (30 mmol/L, see Table 1)  If electrolytes are to be added to CLINIMIX E products, the type and the amount of electrolytes should be dictated by the status of electrolyte balance, disease condition and related vital organ function of the patient.

 For single use only.

Product Monograph Master Template Template Date:

September 2020 CLINIMIX E (Blend C) Page 6 of 31  When used in neonates and children below 2 years, the solution (in bags and administration sets) should be protected from light exposure after admixture through administration.  It is recommended that after opening the bag, the contents should be used immediately, and should not be stored for a subsequent infusion.

Table 1 - The Contents of the Admixed Solution* of CLINIMIX E Amino Acids (Blend C) with Electrolytes in Dextrose Injection. 4 Dextrose (g/L) 100 166 Energy: Total energy from amino acids and dextrose approx. (Kcal/L) 540 764 Energy from dextrose approx.

5 / 5 Phosphate (mmol/L) / (mEq/L) 15 / 30 15 / 30 Chloride (mmol/L) 35 35 Acetate (mmol/L) 75 75 Osmolarity approx. , amino acids and dextrose) should be based on individual nutritional requirements and patient tolerance. The total daily dose of these solutions depends on the patient’s metabolic requirement and clinical response.

The determination of nitrogen balance and accurate daily body weights (corrected for fluid balance), are probably the best means of assessing individual nitrogen requirements. 8 g/kg of body weight for adults. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially.

5 g/kg of body weight for adults and 2 to 3 g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate will be necessary to promote adequate patient response to therapy.

The severity of the illness being treated is the primary consideration in determining proper dose level. Higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation. Care should be exercised to ensure the maintenance of proper levels of serum potassium.

It may be necessary to add additional quantities of this electrolyte to the solution in order to meet the patient’s potassium intake needs. Potassium requirements in a parenteral nutrition (PN) formulation for generally healthy people with normal losses are 1-2 mmol/kg/day, but should be customized to meet individual patient needs.

CLINIMIX E product inherently contains potassium 30 mmol/L, and this should be taken into account prior to any supplemental potassium additions. g. renal failure), acceptable total daily administration volumes are dependent upon the fluid balance requirements of the patient.

Extreme care should be given to prevent fluctuations of blood osmolarity and serum electrolyte concentrations. Frequent and careful monitoring is mandatory when fluid restricted patients are receiving intravenous nutrition. Although CLINIMIX E products contains electrolytes, supplementations may be indicated according to the clinical needs of the patient.

4 Administration). 4 Administration). 4 Administration Preparation of the Product for Administration: Prior to use, the solutions in the two chambers must be thoroughly mixed following the procedure described below. Any additives including electrolytes and lipid emulsion, if needed, should only be added to the mixed solution of the product.

For details on the product packaging, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. Before Mixing:  Do not open the overwrap until ready for use. The […]

The use of all formulations of CLINIMIX E (Amino Acids with Electrolytes in Dextrose Injection) is contraindicated in the following populations / situations:  Known hypersensitivity to any of the substances or component of the container.

For a complete listing, see Table 1 and 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.  Concomitant administration of ceftriaxone in newborns (≤ 28 days of age), even if separate infusion lines are used due to risk of fatal ceftriaxone-calcium salt precipitation in the neonate’s bloodstream.

, via Y-port/Y- site) in patients older than 28 days of age. If the same infusion line is used for sequential administration, the line must be thoroughly flushed between infusions with a compatible fluid.  CLINIMIX E must not be administered to patients with pathologically elevated plasma concentrations of sodium, potassium, magnesium, calcium and/or phosphorus.

 Known allergy to corn or corn products since the products contain corn-derived dextrose  Patients with acute renal failure and without undergoing renal replacement therapy.  Patients with severe liver failure or hepatic coma  Congenital abnormality of amino acid metabolism  Severe hyperglycemia (glucose concentration greater than 180 mg/dL or 10 mmol/L)  Hyperkalemia (see 7 WARNINGS AND PRECAUTIONS)  Hypercalcaemia (see 7 WARNINGS AND PRECAUTIONS)  Hyperphosphatemia (see 7 WARNINGS AND PRECAUTIONS)  Hypernatremia Product Monograph Master Template Template Date: September 2020 CLINIMIX E (Blend C) Page 5 of 31  Hypermagnesemia  Co-administration with calcium-containing intravenous solutions (see 7 WARNINGS AND PRECAUTIONS)

Synthamin 17, 10% Amino Acid Intravenous Infusion provides a biologically available source of nitrogen (L-amino acids) for amino acids synthesis. When administered with an adequate source of energy such as concentrated carbohydrate solutions, minerals and vitamins, the mixture provides (with the exception of essential fatty acids) sufficient parenteral nutrition for patients unable to absorb adequate oral nutrition.

The solution is for administration by intravenous infusion through a central venous catheter with the tip located in the central vena cava. The total daily dose of the solution depends upon the patient’s metabolic requirement and clinical response.

The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements. In addition to meeting nitrogen needs, the rate of administration is governed, especially during the first few days of therapy, by the patient’s ability to tolerate glucose.

Daily intake of amino acids, electrolytes and glucose should be increased gradually to the maximum required dose as indicated by frequent determination of urine and blood sugar levels. 2g/kg of body weight for infants to 56g of protein per day for adults weighing 70kg.

75 megajoules (180kcal) per gram of nitrogen. In the initial treatment of severe trauma or in the presence of marked malnutrition, higher doses of amino acids with correspondingly larger quantities of carbohydrate will be necessary to promote adequate patient response to therapy.

The degree of negative nitrogen balance being treated is the primary consideration in determining replacement therapy. 2). Fat emulsion co-administration should be considered when prolonged parenteral nutrition is required in order to prevent essential fatty acid deficiency (EFAD).

2). The osmolarity of a specific infusion solution must be taken into account when peripheral administration is considered. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

The flow rate should be increased gradually during the first hour. The flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion. Use of a final filter is recommended during administration of all parenteral nutrition solutions.

Paediatric population In children, the dosage of parenteral nutrition should be individually tailored to the amino acid, electrolyte and energy requirements of the patient. 6).

The following adverse reactions have been reported in the post-marketing experience.

Other adverse reactions reported with parenteral amino acid products include:

Tabulated list of adverse reactions System Organ Class Preferred MedDRA Term Frequency Immune system disorders Anaphylactic/anaphylactoid reactions* Hypersensitivity** Not known Not known Vascular disorders Pulmonary vascular precipitate Not known *Including: skin, gastrointestinal and severe circulatory (shock) and respiratory manifestations **Includes the following manifestations: Pyrexia, Chills, Hypotension, Hypertension, Anthralgia, Myalgia, Urticaria, Rash, Pruritus, Erythema, Headache.

Other adverse reactions reported with parenteral amino acid products include: • Azotemia, Hyperammonemia Adverse reactions reported with parenteral nutrition to which the amino acid component may play a causal or contributory role include: • Hepatic failure, Hepatic cirrhosis, Hepatic fibrosis, Cholestasis, Hepatic steatosis, Blood bilirubin increased, Hepatic enzyme increased; Cholecystitis, Cholelithiasis • Infusion site thrombophlebitis; Venous irritation (infusion site phlebitis, pain, erythema, warmth, swelling, induration).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Synthamin is contraindicated in patients with: • Known hypersensitivity to any of the active substances or excipients, or to components of the container • Congenital abnormality of amino acid metabolism Synthamin must not be administered to patients with clinically significant elevation of plasma concentrations of sodium, potassium, magnesium, and/or phosphorus.

Uses:

For temporary relief of minor: urinary discomfort* backache* fatigue* swelling* *Claims based on traditional homeopathic practice, not accepted medical evidence. Not FDA evaluated.

Directions:

Adults & children ages 12 years and over: Take 10 drops under the tongue 3 times a day, or as directed by your healthcare professional. Consult a physician for use in children under 12 years of age.

Stop use and ask a doctor if urinary discomfort, backache, fatigue, swelling, or other symptoms do not improve within 7 days or are accompanied by fever.