Aminosyn-PF Dailymed

Description

Aminosyn^®-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) is a sterile, nonpyrogenic solution for intravenous infusion. Aminosyn-PF 10% is oxygen sensitive. The Pharmacy Bulk Package is a sterile dosage form which contains multiple single doses for use only in a pharmacy bulk admixture program. The formulation is described below:

Aminosyn-PF 10%
An Amino Acid Injection — Pediatric Formula
Essential Amino Acids (mg/100 mL)
Isoleucine	760
Leucine	1200
Lysine (acetate)*	677
Methionine	180
Phenylalanine	427
Threonine	512
Tryptophan	180
Valine	673
* Amount cited is for lysine alone and does not include the acetate salt.

Nonessential Amino Acids (mg/100 mL)
Alanine	698
Arginine	1227
Aspartic Acid	527
Glutamic Acid	820
Glycine	385
Histidine	312
Proline	812
Serine	495
Taurine	70
Tyrosine	44

Electrolytes (mEq/L)
Sodium (Na+)	None
Potassium (K+)	None
Chloride (Cl−)	None
Acetate (C2H3O2 −) a	46

Product Characteristics
Protein Equivalent (Approx. grams/L)	100
Total Nitrogen (grams/L)	15.2
Osmolarity (mOsmol/L)	788
pH (range)	5.5 (5.0 to 6.5)
Specific Gravity	1.03
a From lysine acetate.

The formulas for the individual amino acids present in Aminosyn-PF 10% are as follows:

Essential Amino Acids
Isoleucine	CH3CH2CH(CH3)CH(NH2)COOH
Leucine	(CH3)2CHCH2CH(NH2)COOH
Lysine Acetate	H2N(CH2)4CH(NH2)COOH • CH3COOH
Methionine	CH3S(CH2)2CH(NH2)COOH
Phenylalanine
Threonine	CH3CH(OH)CH(NH2)COOH
Tryptophan
Valine	(CH3)2CHCH(NH2)COOH

Nonessential Amino Acids
Alanine	CH3CH(NH2)COOH
Arginine	H2NC(NH)NH(CH2)3CH(NH2)COOH
L-Aspartic Acid	HOOCCH2CH(NH2)COOH
L-Glutamic Acid	HOOC(CH2)2CH(NH2)COOH
Glycine	H2NCH2COOH
Histidine
Proline
Serine	HOCH2CH(NH2)COOH
Taurine	H2N − CH2CH2− SO3H
Tyrosine

The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly.

Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials.

Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.

The Pharmacy Bulk Package is designed for use with manual, gravity flow operations and automated compounding devices for preparing sterile parenteral nutrient admixtures; it contains no bacteriostat. Multiple single doses may be dispensed during continual aliquoting operations. Withdrawal of container contents should be promptly completed within 4 hours after initial closure puncture.

Clinical Pharmacology

Aminosyn-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) contains a mixture of essential and nonessential amino acids as well as taurine. The amino acid composition has been specifically formulated to provide a well-tolerated nitrogen source for nutritional support and therapy for infants and young children. When administered in conjunction with a cysteine hydrochloride additive, Aminosyn-PF 10% results in plasma amino acid concentrations approximating a profile consistent with that of a breast-fed infant.

The rationale for Aminosyn-PF 10% is based on the observation of inadequate levels of essential amino acids in the plasma of infants receiving total parenteral nutrition (TPN) using conventional amino acid solutions.

Clinical studies in infants who required TPN therapy showed that infusion of Aminosyn-PF 10% resulted in plasma amino acid concentrations approximating those of normal breast or formula fed infants. 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, supplemented with cysteine hydrochloride, electrolytes, vitamins, and minerals, Aminosyn-PF 10% provides TPN for infants and young children, with the exception of essential fatty acids.

It is thought that the acetate from lysine acetate under the conditions of parenteral nutrition, does not impact net acid-base balance when renal and respiratory functions are normal. Clinical evidence seems to support this thinking; however, confirmatory experimental evidence is not available. The amounts of sodium and acetate in Aminosyn-PF 10% are not of clinical significance.

The addition of a cysteine hydrochloride additive will contribute to the chloride load.

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

The human newborn conjugates bile with taurine which becomes the primary method of biliary excretion. Taurine deficiency because of its effect on bile salt conjugation and, therefore, on bile salt flow may be of major importance in the genesis of cholestasis. Taurine has also been shown to play a role in central nervous system development.

Indications And Usage

Aminosyn-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) is indicated for the nutritional support of infants (including those of low birth weight) and young children requiring TPN via either central or peripheral infusion routes. Parenteral nutrition with Aminosyn-PF 10% is indicated to prevent nitrogen and weight loss or treat negative nitrogen balance in infants and young children where (1) the alimentary tract by the oral gastrostomy, or jejunostomy route, cannot or should not be used or adequate protein intake is not feasible by these routes; (2) gastrointestinal absorption of protein is impaired; or (3) protein requirements are substantially increased as with extensive burns. Dosage, route of administration, and concomitant infusion of non-protein calories are dependent on various factors, such as nutritional and metabolic status of the patient, anticipated duration of parenteral nutrition support, and vein tolerance. See DOSAGE AND ADMINISTRATION for additional information.

Central Venous Infusion

Central venous infusion should be considered when amino acid solutions are to be admixed with hypertonic dextrose to promote protein synthesis in hypercatabolic or severely depleted infants or those requiring long-term parenteral nutrition.

Peripheral Parenteral Nutrition

For moderately catabolic or depleted patients in whom the central venous route is not indicated, diluted amino acid solutions mixed with 5 to 10% dextrose solutions may be infused by peripheral vein, supplemented, if desired, with fat emulsion.

Safe, effective use of parenteral nutrition requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of the complications which can occur. FREQUENT EVALUATION AND LABORATORY DETERMINATIONS ARE NECESSARY FOR PROPER MONITORING OF PARENTERAL NUTRITION. Studies should include blood sugar, serum proteins, kidney and liver function tests, electrolytes, hemogram, carbon dioxide content, serum osmolalities, blood cultures, and blood ammonia levels.

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.

Administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentrations of the solutions.

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

Hyperammonemia is of special significance in infants , as its occurrence in the syndrome caused by genetic metabolic defects is sometimes associated, although not necessarily in a causal relationship, with mental retardation. This reaction appears to be dose-related and is more likely to develop during prolonged therapy. It is essential that blood ammonia levels be measured frequently in infants.

Conservative doses of amino acids should be given, dictated by the nutritional status of the patient. Should symptoms of hyperammonemia develop, amino acid dosage levels should be reduced and titrated against serum ammonia levels.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature 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 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.

Precautions

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require the use of additional electrolyte supplements.

Strongly hypertonic nutrient solutions should be administered via an intravenous catheter placed in a central vein, preferably the superior vena cava.

Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency.

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

Administration of glucose at a rate exceeding the patient’s utilization rate may lead to hyperglycemia, coma, and death.

The effect of infusion of amino acids, without dextrose, upon carbohydrate metabolism of children is not known at this time. It is essential to provide adequate exogenous dextrose calories concurrently with amino acids. Administration of amino acids without carbohydrates may result in the accumulation of ketone bodies in the blood. Correction of this ketonemia may be achieved by the administration of carbohydrate.

Essential fatty acid deficiency (EFAD) is becoming increasingly recognized in patients on long term TPN (more than 5 days). The use of fat emulsion to provide 4 — 10% of total caloric intake as linoleic acid may prevent EFAD.

Peripheral administration of Aminosyn-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) 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 infusion or change infusion site and initiate appropriate treatment.

Extraordinary electrolyte losses such as may occur during protracted nasogastric suction, vomiting, diarrhea, or gastrointestinal fistula drainage may necessitate additional electrolyte supplementation.

Metabolic acidosis can be prevented or readily controlled by adding a portion of the cations in the electrolyte mixture as acetate salts and in the case of hyperchloremic acidosis, by keeping the total chloride content of the infusate to a minimum.

Aminosyn-PF 10% contains no chloride.

Aminosyn-PF 10% 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. To assure adequate intake, serum levels should be monitored frequently.

Aminosyn-PF 10% contains no more than 25 mcg/L of aluminum.

To minimize the risk of possible incompatibilities arising from mixing this solution 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.

BOXED WARNING SECTION

SPECIAL PRECAUTIONS FOR

CENTRAL INFUSIONS

ADMINISTRATION BY CENTRAL VENOUS CATHETER SHOULD BE

USED ONLY BY THOSE FAMILIAR WITH THIS TECHNIQUE

AND ITS COMPLICATIONS.

Central vein infusion (with added concentrated carbohydrate solutions) of amino acid solutions requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of complications. Attention must be given 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.

SUMMARY HIGHLIGHTS OF COMPLICATIONS (See also Current Medical Literature).

• 
  Technical
  
  The placement of a central venous catheter should be regarded as a surgical procedure. One should be fully acquainted with various techniques of catheter insertion. For details of technique 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 and air and catheter emboli.
  
• 
  Septic
  
  The constant risk of sepsis is present during administration of total parenteral nutrition. It is imperative that the preparation of the solution and the placement and care of catheters be accomplished under strict aseptic conditions.
  
  Solutions should ideally be prepared in the hospital pharmacy under a laminar flow hood using careful aseptic technique to avoid inadvertent touch contamination. Solutions should be used promptly after mixing. Storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.
  
  Administration time for a single container and set should never exceed 24 hours.
  
• 
  Metabolic
  
  The following metabolic complications have been reported with TPN administration: Metabolic acidosis and alkalosis, hypophosphatemia, hypocalcemia, osteoporosis, hyperglycemia and glycosuria, rebound hypoglycemia, osmotic diuresis and dehydration, elevated liver enzymes, hypo- and hypervitaminosis, electrolyte imbalances and hyperammonemia in children. Frequent evaluations are necessary especially during the first few days of therapy to prevent or minimize these complications.
  
  Administration of glucose at a rate exceeding the patient’s utilization rate may lead to hyperglycemia, coma and death. CLINICAL EVALUATION AND LABORATORY DETERMINATIONS, AT THE DISCRETION OF THE ATTENDING PHYSICIAN ARE NECESSARY FOR PROPER MONITORING DURING ADMINISTRATION. Do not withdraw venous blood for blood chemistries through the peripheral infusion site, as interference with estimations of nitrogen-containing substances may occur. Blood studies should include glucose, urea nitrogen, serum electrolytes, ammonia, cholesterol, acid-base balance, serum proteins, kidney and liver function tests, osmolarity and hemogram. White blood count and blood cultures are to be determined if indicated. Urinary osmolality and glucose should be determined as necessary.
  

Pregnancy Category C

Animal reproduction studies have not been conducted with Aminosyn-PF 10%. It is also not known whether Aminosyn-PF 10% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Aminosyn-PF 10% should be given to a pregnant woman only if clearly needed.

Adverse Reactions

Local reactions consisting of erythema, phlebitis and thrombosis at the infusion site have occurred with peripheral intravenous infusion of amino acids particularly if other substances, such as antibiotics, are also administered through the same site. In such cases the infusion site should be changed promptly to another vein. Use of large peripheral veins, inline filters, and slowing the rate of infusion may reduce the incidence of local venous irritation. Electrolyte additives should be spread throughout the day. Irritating additive medications may need to be injected at another venous site.

Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino acid solutions.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

Overdosage

In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS and PRECAUTIONS .