Primene (Amino Acids)

PRIMENE®

Clintec

Amino Acids

I.V. Nutritive Supplement

Action And Clinical Pharmacology: Primene is a sterile, nonpyrogenic, hypertonic solution of essential and nonessential amino acids in a Pharmacy Bulk Package. A Pharmacy Bulk Package is a container of a sterile preparation for parenteral use in a pharmacy admixture program and is restricted to the preparation of admixtures for i.v. infusion.

Primene provides a mixture of essential and nonessential amino acids as well as taurine and cysteine. This amino acid injection has been specifically formulated to provide a well tolerated nitrogen source for nutritional support for neonates, infants and young children. The amino acid profile corresponds qualitatively and quantitatively to the protein needs in this patient population. Of the total amino acids, essential amino acids comprise 47.5% and branched chain amino acids comprise 24%.

Clinical studies in infants and young children who required TPN therapy showed that infusion of Primene resulted in a normalization of the plasma amino acid concentrations. In addition, weight gains, nitrogen balance, and serum protein concentrations were consistent with an improving nutritional status.

When infused with hypertonic dextrose as a calorie source, electrolytes, vitamins, and minerals, Primene provides total parenteral nutrition in infants and young children, with the exception of essential fatty acids.

The amounts of chloride present in Primene are not of clinical significance.

The electrolyte content of any additives that are introduced should be carefully considered and included in total input computations.

Indications And Clinical Uses: The nutritional support of infants (including those of low birth weight) and young children requiring TPN via either central or peripheral infusion routes. The purpose of the solution is to prevent nitrogen and weight loss or treat negative nitrogen balance in infants and young children where: the alimentary tract cannot or should not be used, gastrointestinal absorption of protein is impaired, or metabolic requirements for protein are substantially increased, as with extensive burns.

Contra-Indications: In patients with untreated anuria, hepatic coma, inborn errors of amino acid metabolism, including those involving branched chain amino acid metabolism such as maple syrup urine disease and isovaleric acidemia, or hypersensitivity to one or more amino acids present in the solution.

Manufacturers’ Warnings In Clinical States: This solution is for compounding only, not for direct infusion.

Proper administration of this injection requires knowledge of fluid and electrolyte balance and nutrition as well as clinical expertise in recognition and treatment of the complications which may occur.

Frequent clinical evaluation and laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentration, osmolarity, and acid base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Studies should include blood sugar, serum proteins, blood ammonia levels, kidney and liver function tests, electrolytes, hemogram, arterial blood gases, serum osmolarities and blood cultures.

Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino acid imbalances, hyperammonemia, prerenal azotemia, stupor and coma.

The i.v. administration of these solutions can lead to fluid or solute overload resulting in hyper or hypoosmolal states. The risk of hypoosmolal states is especially present in conditions associated with ADH secretion and is proportional to the infusion rate. Hyperammonemia is of special significance in infants. This reaction appears to be related to a deficiency of the urea cycle enzymes of genetic or product origin. It is essential that blood ammonia be measured frequently in infants.

Conservative doses of this injection should be given to patients with known or suspected hepatic dysfunction. Should symptoms of hyperammonemia develop, administration should be discontinued and the patient’s clinical status re-evaluated.

Administration of amino acids in the presence of impaired renal function or gastrointestinal bleeding may augment an already elevated blood urea nitrogen. Patients with azotemia from any cause should not be infused with amino acids without regard to total nitrogen intake.

This injection should not be administered simultaneously with blood through the same infusion set because of the possibility of pseuodoagglutination.

Precautions: It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis. Concentrated dextrose solutions are an effective source of such calories. With the administration of Primene in combination with highly concentrated dextrose solutions, hyperglycemia, glycosuria and hyperosmolar syndrome may result. Blood and urine glucose should be monitored on a routine basis in patients receiving this therapy.

Sudden cessation in administration of a concentrated dextrose solution may result in insulin reaction due to continued endogenous production. Parenteral nutrition mixtures should be withdrawn slowly.

Special care must be taken when giving hypertonic dextrose to a diabetic or prediabetic patient. To prevent severe hyperglycemia in such patients, insulin may be required.

Electrolytes may be added with this injection as dictated by the patient’s electrolyte profile.

Strongly hypertonic nutrient solutions should be administered through an indwelling i.v. catheter with the tip located in the superior vena cava.

Peripheral administration of Primene requires appropriate dilution and provision of adequate calories. Care should be taken to assure proper placement of the needle within the lumen of the vein. The venipuncture site should be inspected frequently for signs of infiltration. If venous thrombosis or phlebitis occurs, discontinue infusions or change infusion site and initiate appropriate treatment.

Because of its antianabolic activity, concurrent administration of tetracycline may reduce the protein-sparing effects of infused amino acids.

During administration of amino acids in the absence of supporting carbohydrate metabolism, an accumulation of ketone bodies in the blood often occurs. Correction of ketonemia usually can be accomplished by administering some carbohydrates.

Primene contains no added electrolytes. Patients, especially those with hypophosphatemia, may require the addition of phosphate. To prevent hypocalcemia, calcium supplementation should always accompany phosphate administration. To assure adequate intake, serum levels should be monitored frequently.

To minimize the risk of possible incompatibilities arising from mixing this injection with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration.

Unit must be used with a vented set or a nonvented set with a vented spike adapter.

Special Precautions: Administration of amino acid solutions and other nutrients via central or peripheral venous catheter may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure. This includes attention to solution preparation, administration and patient monitoring. It is essential that a carefully prepared protocol, based on current medical practices, be followed, preferably by an experienced team.

Although a detailed discussion of the complications is beyond the scope of this insert, the following summary lists those based on current literature:

Technical: The placement of a central venous catheter should be regarded as a surgical procedure. The physician should be fully acquainted with various techniques of catheter insertion as well as recognition and treatment of complications. For details of techniques and placement sites, consult the medical literature. X-ray is the best means of verifying catheter placement. Complications known to occur from the placement of central venous catheters are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, cardiac arrhythmia and catheter embolus.

Septic: The constant risk of sepsis is present during administration of parenteral nutrition solutions. Since contaminated solutions and infusion catheters are potential sources of infection, it is imperative that the preparation of the solution and the placement and care of catheters be accomplished under controlled aseptic conditions. If fever develops, the solution, its delivery system and the site of the indwelling catheter should be changed. Blood cultures should be taken and the remainder of fluid should be saved for examination when deemed necessary.

Solutions ideally should be prepared in the hospital pharmacy under a laminar flow hood. The key factor in their preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and addition of other nutrients.

These solutions should be used promptly after admixing. Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.

Metabolic: The following metabolic complications have been reported: metabolic acidosis, hypophosphatemia, alkalosis, hyperglycemia and glycosuria, osmotic diuresis and dehydration, rebound hypoglycemia, elevated liver enzymes, hypo and hyper vitaminosis, electrolyte imbalances and hyperammonemia. Frequent clinical evaluation and laboratory determinations are necessary, especially during the first few days of therapy, to prevent or minimize these complications.

Adverse Reactions: See Warnings and Precautions, Special Precautions.

In cases of excessive administration, there is a possibility of metabolic acidosis and of elevated blood urea nitrogen in children with renal insufficiency.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See Warnings and Precautions.

Dosage And Administration: The total daily dose of Primene depends on daily protein requirements and on the patient’s metabolic 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 protein requirements. Dosage should also be guided by the patient’s fluid intake limits and glucose and nitrogen tolerances, as well as by metabolic and clinical response.

The recommended dosage of Primene is 1.5 to 3.5 g of amino acids/kg body weight/day.

Typically, Primene is admixed with 50% dextrose and supplemented with electrolytes and administered continuously over a 24 hour period.

The healthy newborn child requires 2.2 g/kg of protein and 120 kcal/kg/day. For premature infants, especially those in catabolic state, these requirements could be even higher.

Total daily fluid intake should be appropriate for the patient’s age and size. A fluid dose of 125 mL/kg body weight/day is appropriate for most infants on TPN. Provision of additional nitrogen may not be possible due to fluid intake limits, nitrogen, or glucose intolerance. In addition, the provision of sufficient intracellular electrolytes, principally potassium, magnesium, and phosphate, is required for optimum utilization of amino acids, and sufficient quantities of the major extracellular electrolytes sodium, calcium, and chloride, must be given. Therefore if oral feeding is not possible or advisable and TPN is necessary, the volume restrictions dictate how to administer Primene, dextrose and most electrolytes in the same hypertonic solution through i.v. lines. Even such hypertonic solutions will not provide the required daily calories. If prolonged TPN is required (5 days or more), i.v. lipid emulsions will also have to be administered. The following scenario can serve as an example. See Table I.

Premature baby, weight 1 kg, requiring 2.5 g/kg of amino acid/day and 125 mL/kg/day fluid volume.

When prolonged parenteral nutrition (more than 5 days) is required fat emulsion should also be considered in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat free total parenteral nutrition.

In patients with hyperchloremic or other metabolic acidoses, sodium and potassium may be added as the acetate salts to provide bicarbonate precursor. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently.

Additional electrolytes and trace elements should be administered as required.

Central Vein Administration: When enteral feeding is inadvisable, Primene given by central venous infusion in combination with energy sources, vitamins, trace elements and electrolytes, will meet the requirements for weight maintenance or weight gain, depending on the dose selected. The energy component in parenteral nutrition by central infusion may be derived solely from dextrose or may be provided by a combination of dextrose and i.v. fat emulsion. The addition of i.v. fat emulsion provides essential fatty acids and permits a dietary balance of fat and carbohydrate, at the same time offering the option of reducing the dextrose load and/or increasing the total caloric input. An adequate energy supply is essential for optimal utilization of amino acids.

Hypertonic mixtures of amino acids and dextrose may be administered safely by continuous infusion through a central vein catheter with the tip located in the vena cava. Initial infusion rates should be slow, and gradually increased to the recommended 60 to 120 mL/kg body weight/day. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient’s tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of urine and blood sugar levels.

Peripheral Vein Administration: For patients requiring parenteral nutrition in whom the central vein route is not indicated, this injection can be mixed with low concentration dextrose solutions and administered by peripheral vein in conjunction with or without fat emulsions. Reduction of protein loss can be achieved by use of diluted Primene in combination with dextrose or with dextrose and i.v. fat emulsion by peripheral infusion. Complete peripheral i.v. nutrition can be achieved in patients with low caloric requirements by a Primene-dextrose-fat regimen.

In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria.

Parenteral nutrition may be started with infusates containing lower concentrations of dextrose; dextrose content may be gradually increased to estimated caloric needs as the patient’s glucose tolerance increases.

Sudden cessation in administration of concentrated dextrose solution may result in insulin reaction due to continued endogenous insulin production. Such solutions should be withdrawn slowly.

I.V. fat emulsions provide approximately 1.2 kcal/mL (10%) or 2 kcal/mL (20%) and may be administered along with amino acid-dextrose solutions by means of a short Y-connector near the infusion site to supplement caloric intake. Fat, however, should not be the sole caloric intake since studies have indicated that glucose is more nitrogen sparing in the stressed patient.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.

A slight yellow color does not alter the quality and efficacy of the product.

Primene in the Pharmacy Bulk Package is intended for use in the preparation of sterile, i.v. admixtures. Additives may be incompatible with the fluid withdrawn from this container. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of Primene.

Solutions should be used promptly after mixing. Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.

Directions for Use of the Pharmacy Bulk Package Container: For compounding only, not for direct infusion: 1. The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). 2. Remove outer seal and metal disc. Swab surface of stopper using approved technique. 3. Insert vented connector of solution transfer set and suspend unit. Refer to directions accompanying set. 4. Once container closure has been penetrated, withdrawal of contents should be completed without delay. After initial entry, maintain contents at room temperature (25°C) and dispense within 4 hours.

Stability and Storage Recommendations: Exposure of pharmaceutical products to heat should be minimized. Solutions should be used promptly after admixing. Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours. Protect from freezing. It is recommended the product be stored at temperatures between 15 and 25°C, protected from light.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible. A slight yellow color does not alter the quality and efficacy of the product.

Parenteral Products: To minimize the risk of possible incompatibilities arising from mixing this injection with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of Primene.

Availability And Storage: Each 100 mL contains

Glass pharmacy bulk package of 250 mL.

PRIMENE® Clintec Amino Acids I.V. Nutritive Supplement

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