Mixing with confidence: stability and compatibility resources for parenteral nutrition (PN)
PN is an important therapeutic intervention for patients of all ages managed across care settings—from the intensive care unit to the home.1 Compromised stability and/or compatibility of a PN admixture can have serious consequences for patients—yet the terms are often conflated. Understanding the distinction is essential for safe compounding and administration.
Stability and compatibility—what’s the difference?
Stability refers to maintaining the integrity―both chemical and physical―of the components within a formulation over time, avoiding any instability, which is typically irreversible.1
Compatibility refers to the ability of 2 or more components to be combined without producing a physical or chemical reaction—whether visible or not—that alters the formulation or compromises its safety.1
Compatibility asks: Can these components coexist? Stability asks: Will they stay that way? Both questions must be answered before administering a PN admixture.
Factors influencing stability and compatibility of a PN admixture
A PN admixture may include amino acids, dextrose, lipid injectable emulsion (ILE), and numerous additives (ie, electrolytes, vitamins, and trace elements). ILEs are essential components of PN as sources of energy and essential fatty acids; however, they are inherently unstable systems and, over time, may undergo various stages of destabilization.1 The stability and compatibility of an ILE when mixed with amino acids and dextrose depend on:
- pH: ILEs are most stable at pH 7-8. Dextrose is acidic and lowers the final admixture pH; amino acids are buffers and the rate-limiting factors for admixture stability.1-3
- Macronutrient concentrations: Based on soybean oil ILE data, minimum final concentrations of dextrose ≥10%, amino acids ≥4%, and ILE ≥2% are generally required for admixture stability (the “10/4/2 rule”). These concentrations may differ between ILE products.1,4 Refer to the manufacturer’s stability data for specific concentrations.
- Micronutrients: Calcium, magnesium, and iron can neutralize the emulsifier’s surface charge and destabilize the emulsion.3
- Light and oxygen: Exposure to light and oxygen can degrade lipids and vitamins within an ILE, making them unstable. The American Society for Parenteral and Enteral Nutrition (ASPEN) recommends photoprotection of PN admixtures and ILEs for neonates.4
PN administration considerations
PN can be administered as a total nutrient admixture (TNA) or co-infused via a Y-site connection.
- TNAs combine all macronutrients, including the ILE, in a single bag. Stability must be maintained across the full beyond-use period, and data are product and formulation specific.1
- Results from one amino acid or ILE product cannot be extrapolated to another.3
- Y-site connections permit co-infusion of an ILE with another PN or a PN with a medication.2
- Stability and compatibility should be verified using product-specific data and should not be assumed based on visual inspection or prior experience.
SMOFlipid® and Omegaven® stability and compatibility resources
As the US market leader in ILEs,5 Fresenius Kabi is excited to offer stability and compatibility resources for SMOFlipid (lipid injectable emulsion), for intravenous use, and Omegaven (fish oil triglycerides) injectable emulsion, for intravenous use, to help clinicians make informed, evidence-based decisions.
Under the resources page, you will find SMOFlipid and Omegaven Admixture Stability Reference Guides for Adults and Pediatrics, Y-Site Drug Compatibility Guides, and other helpful SMOFlipid and Omegaven resources that are backed by current guidelines and robust data.
- SMOFlipid is the first and only 4-oil ILE—combining soybean oil, medium-chain triglycerides, olive oil, and fish oil—approved for use in adult and pediatric patients.6
- Omegaven is the first and only fish oil ILE approved in the US as a source of calories and fatty acids in pediatric patients with PN-associated cholestasis.7
Fresenius Kabi is committed to bringing more to PN—and these resources reflect that commitment.
Fresenius Kabi Product Resources and Informative Podcasts
SMOFlipid (lipid injectable emulsion), for intravenous use
IMPORTANT SAFETY INFORMATION
What is SMOFlipid?
- Indicated in adult and pediatric patients as a source of calories and essential fatty acids for parenteral nutrition (PN) when oral or enteral nutrition is not possible, insufficient, or contraindicated.
- The hourly infusion rate in pediatrics should not exceed 0.75 mL/kg/hour and 0.5 mL/kg/hour in adults.
SMOFlipid should not be received by patients who have:
- A known allergy to fish, egg, soybean, or peanut, or to any of the active or inactive ingredients in SMOFlipid.
- Abnormally high levels of lipid (triglycerides) in the blood.
SMOFlipid may cause serious side effects including:
- Serious Adverse Reactions with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants: Strictly follow the recommended total daily dosage and do not exceed the maximum infusion rate. If poor clearance of fats occurs, the infusion should be stopped, and a medical evaluation started.
- Risk of Parenteral Nutrition-Associated Liver Disease: Parenteral nutrition-associated liver disease (PNALD) may progress to liver inflammation and damage caused by a buildup of fat in the liver with scarring and cirrhosis.
- Allergic Reactions: Contact your healthcare provider immediately if you are experiencing an allergic reaction.
- Fat Overload Syndrome, Refeeding Syndrome, Elevated Triglycerides (Hypertriglyceridemia): Your healthcare provider will monitor you for signs and symptoms of early infection and blood levels.
Monitoring/Laboratory Tests: The content of vitamin K may interfere with blood clotting activity of medications.
The most common side effects (>1%) in adult patients include nausea, vomiting, and high levels of glucose in the blood and in pediatric patients include low levels of red blood cells, vomiting, increased levels of liver enzymes (i.e., gamma-glutamyltransferase) and hospital-acquired infections.
These are not all the possible side effects associated with SMOFlipid. Call your healthcare provider for medical advice regarding SMOFlipid side effects. You are encouraged to report negative side effects of SMOFlipid. Contact Fresenius Kabi USA, LLC at: 1-800-551-7176 or FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch. The FDA-approved product labeling can be found at https://freseniuskabinutrition.com/SMOFlipidPI.
OMEGAVEN (fish oil triglycerides) injectable emulsion, for intravenous use
IMPORTANT SAFETY INFORMATION
These highlights do not include all the information needed to use OMEGAVEN safely and effectively. To learn more about OMEGAVEN for your child, talk to your child’s healthcare provider. OMEGAVEN is available by prescription only. The FDA-approved product labeling can be found at https://freseniuskabinutrition.com/OmegavenPI.
What is OMEGAVEN?
- A fish oil-based intravenous lipid emulsion that is a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC).
- Does not prevent PNAC.
- It has not been demonstrated that the clinical outcomes seen in pediatric patients are a result of the omega-6:omega-3 fatty acid ratio of the product.
- The hourly infusion rate should not exceed 1.5 mL/kg/hour
OMEGAVEN should not be received by patients who have:
- a known allergy to fish or egg protein or to any of the ingredients in OMEGAVEN.
- a severe bleeding disorder.
- abnormally high levels of lipid (triglycerides) in the blood.
What important safety information should I know about OMEGAVEN?
- Serious Adverse Reactions with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants: Strictly follow the recommended total daily dosage and do not exceed the maximum infusion rate. If poor clearance of fats occurs, the infusion should be stopped, and a medical evaluation started.
- Allergic Reactions: Contact your healthcare provider immediately if you are experiencing an allergic reaction.
- Fat Overload Syndrome, Refeeding Syndrome, Elevated Triglycerides (Hypertriglyceridemia): Your healthcare provider will monitor you for signs and symptoms of early infection and blood levels.
The most common side effects, (>15%) include: vomiting, agitation, slower than normal heartbeat, interruption of breathing, and viral infection.
These are not all the possible side effects associated with OMEGAVEN. Call your healthcare provider for medical advice regarding OMEGAVEN side effects. You are encouraged to report negative side effects of OMEGAVEN. Contact Fresenius Kabi USA, LLC at: 1-800-551-7176 or FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch. The FDA-approved product labeling can be found at https://freseniuskabinutrition.com/OmegavenPI.