Perikabiven - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
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Perikabiven - Scientific Information

Manufacture: Fresenius Kabi USA, LLC
Country: United States
Condition: Total Parenteral Nutrition
Class: Intravenous nutritional products
Form: Liquid solution, Intravenous (IV)
Ingredients: Dextrose monohydrate, soybean oil, sodium acetate, potassium chloride, sodium glycerophosphate anhydrous, magnesium sulfate heptahydrate, calcium chloride, lysine hydrochloride, phenylalanine, leucine, valine, threonine, methionine, isoleucine, tryptophan, alanine, arginine, glycine, proline, histidine, glutamic acid, serine, aspartic acid, tyrosine, egg phospholipids, glycerin, water, sodium hydroxide, acetic acid.

Description

PERIKABIVEN is a sterile, hypertonic emulsion, for peripheral or central venous administration, in a Three Chamber Bag. The product contains no added sulfites.

Chamber 1 contains Dextrose solution for fluid replenishment and caloric supply.

Chamber 2 contains the Amino Acid solution with Electrolytes, which comprises essential and nonessential amino acids provided with electrolytes.

Chamber 3 contains Intralipid 20% (a 20% Lipid Injectable Emulsion), prepared for intravenous administration as a source of calories and essential fatty acids.

See below for formulations of each chamber and Table 2 for strength, pH, osmolarity, ionic concentration and caloric content of PERIKABIVEN when all the chambers are mixed together.

Chamber 1: Contains sterile, hypertonic solution of Dextrose, USP in water for injection with a pH range of 3.5 to 5.5. Dextrose, USP is chemically designated D-glucose, monohydrate (C6H12O6 • H2O) and has the following structure:

Chamber 2: Contains a sterile solution of amino acids and electrolytes in water for injection. In addition, glacial acetic acid has been added to adjust the pH so that the final solution pH is 5.4 to 5.8. The formulas for the individual electrolytes and amino acids are as follows:

Electrolytes
Sodium Acetate Trihydrate, USP CH3COONax3H2O
Potassium Chloride, USP KCl
Sodium Glycerophosphate C3H5(OH)2PO4Na2xH2O
Magnesium Sulfate Heptahydrate, USP MgSO4x7H2O
Calcium Chloride Dihydrate, USP CaCl2x2H2O
Essential Amino Acids
Lysine (added as the hydrochloride salt) H2N(CH2)4CH(NH2)COOH.HCl
Phenylalanine
Leucine (CH3)2CHCH2CH(NH2)COOH
Valine (CH3)2CHCH(NH2)COOH
Threonine CH3CH(OH)CH(NH2)COOH
Methionine CH3S(CH2)2CH(NH2)COOH
Isoleucine CH3CH2CH(CH3)CH(NH2)COOH
Tryptophan
Nonessential Amino Acids
Alanine CH3CH(NH2)COOH
Arginine H2NC(NH)NH(CH2)3CH(NH2)COOH
Glycine H2NCH2COOH
Proline
Histidine
Glutamic Acid HOOC(CH2)2CH(NH2)COOH
Serine HOCH2CH(NH2)COOH
Aspartic Acid HOOCCH2CH(NH2)COOH
Tyrosine

Chamber 3: Contains a 20% Lipid Injectable Emulsion (Intralipid 20%) which is made up of 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and water for injection. In addition, sodium hydroxide has been added to adjust the pH. The final product pH range is 6 to 9.

The soybean oil is a refined natural product consisting of a mixture of neutral triglycerides of predominantly unsaturated fatty acids with the following structure:

where andare saturated and unsaturated fatty acid residues. The major component fatty acids are linoleic (48 to 58 %), oleic (17 to 30%), palmitic (9 to 13%), linolenic (5 to 11%) and stearic acid (2.5 to 5%). These fatty acids have the following chemical and structural formulas:

Linoleic acid
C18H32O2
Oleic acid
C18H34O2
Palmitic acid
C16H32O2
Linolenic acid
C18H30O2
Stearic acid
C18H36O2

Purified egg phosphatides are a mixture of naturally occurring phospholipids which are isolated from the egg yolk. These phospholipids have the following general structure:

andcontain saturated and unsaturated fatty acids that abound in neutral fats. R3 is primarily either the choline or ethanolamine ester of phosphoric acid.

Glycerin is chemically designated C3H8O3 and is a clear colorless, hygroscopic syrupy liquid. It has the following structural formula:

The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional oxygen and moisture barrier when necessary. An oxygen absorber is placed between the inner bag and the overpouch.

The container is not made with natural rubber latex or polyvinyl chloride (PVC).

Clinical Pharmacology

Mechanism of Action

PERIKABIVEN is used as a supplement or as the sole source of nutrition in patients, providing macronutrients (amino acids, dextrose and lipids) and micronutrients (electrolytes) 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.

The administered dextrose is oxidized to carbon dioxide and water, yielding energy.

Intravenously administered lipids provide a biologically utilizable source of calories and essential fatty acids. Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy derived from fatty acid metabolism is beta- oxidation. Fatty acids are important for membrane structure and function, precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression.

Pharmacokinetics

The infused lipid particles provided by PERIKABIVEN are expected to be cleared from the blood stream in a manner thought to be comparable to the clearing of chylomicrons. In healthy volunteers, the maximum clearance rate of the triglycerides after fasting overnight has been found to be 3.8 ± 1.5 g/kg per 24 hours.

Both elimination and oxidation rates are dependent on the patient's clinical condition; elimination is faster and utilization is increased in postoperative patients, in sepsis, burns and trauma, while patients with renal impairment and hypertriglyceridemia may show lower utilization of exogenous lipid emulsions. Due to differences in elimination, patients with these conditions should be closely monitored during PERIKABIVEN administration [see Warnings and Precautions].

The disposition of infused amino acids, dextrose and electrolytes are essentially the same as those supplied by ordinary food.

A clinical study in healthy volunteers employing high intravenous doses (80 mmol) of either sodium glycerophosphate used in PERIKABIVEN or reference, inorganic sodium phosphate demonstrated that both compounds resulted in comparable serum inorganic phosphate concentrations after a single intravenous dose. Changes from baseline in the serum levels of sodium, potassium and total calcium were comparable across the two phosphate sources in this study.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been conducted to evaluate carcinogenic potential of PERIKABIVEN or its effect on fertility. Genotoxicity studies have not been conducted with PERIKABIVEN to assess its mutagenic potential.