Data from FDA - Curated by EPG Health - Last updated 30 August 2017


1 INDICATIONS AND USAGE Smoflipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. Limitations of Use The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in Smoflipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions [See Clinical Studies (14)]. Smoflipid is indicated in adults as a source of calories and essential fatty acids for parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated.(1) Limitations of Use The omega-6: omega-3 fatty acid ratio and Medium Chain Triglycerides in Smoflipid have not been shown to improve clinical outcomes compared to other intravenous lipid emulsions. (1)

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Advisory information

4 CONTRAINDICATIONS Use of Smoflipid is contraindicated in patients with: Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients, or Severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentrations > 1,000 mg/dL) [see Warnings and Precautions (5.8)] Known hypersensitivity to fish, egg, soybean, or peanut protein, or to any of the active ingredients or excipients. (4) Severe hyperlipidemia or severe disorders of lipid metabolism with serum triglycerides > 1,000 mg/dL. (4, 5.8)
Adverse reactions
6 ADVERSE REACTIONS Adverse reactions described elsewhere in labeling: Death in Preterm Infants [see Warnings and Precautions (5.1)] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Risk of Catheter-Related Infections [see Warnings and Precautions (5.3) ] Fat Overload Syndrome [see Warnings and Precautions (5.4) ] Refeeding Syndrome [see Warnings and Precautions (5.5) ] Aluminum Toxicity [see Warnings and Precautions (5.6) ] Risk of Parenteral Nutrition-Associated Liver Disease [see Warnings and Precautions (5.7) ] Hypertriglyceridemia [see Warnings and Precautions (5.8) ] Most common adverse drug reactions (>1%) from clinical trials were nausea, vomiting, hyperglycemia, flatulence, pyrexia, abdominal pain, increased blood triglycerides, hypertension, sepsis, dyspepsia, urinary tract infection, anemia and device related infection. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety database for Smoflipid reflects exposure in 229 patients exposed for 5 days to 4 weeks in 5 clinical trials. The pooled population exposed to Smoflipid was adult patients up to 89 years old (20 to 89 years of age), 43% female, and 99% Caucasian. The most frequently reported medical histories in the Smoflipid group were surgical and medical procedures (84%), neoplasms (57%), gastrointestinal disorders (53%), vascular disorders (37%), and infections and infestations (20%). Smoflipid was used as a component of PN which also included dextrose, amino acids, vitamins, and trace elements. Two of the 5 studies were performed with Smoflipid as a component of PN delivered in a 3‑chamber bag. Adverse reactions occurring in at least 1% of patients who received Smoflipid are shown in Table 2. Table 2: Adverse Reactions in > 1% of Patients Treated with Smoflipid Adverse Reaction Number of Patients in Smoflipid Group (N=229) Number of Patients in Comparator Group (N=230) Nausea 20 (9%) 26 (11%) Vomiting 15 (7%) 12 (5%) Hyperglycemia 12 (5%) 5 (2%) Flatulence 10 (4%) 4 (2%) Pyrexia 9 (4%) 11 (5%) Abdominal pain 8 (4%) 5 (2%) Blood triglycerides increased 6 (3%) 4 (2%) Hypertension 6 (3%) 9 (4%) Sepsis 5 (2%) 4 (2%) Dyspepsia 5 (2%) 1 (0%) Urinary tract infection 4 (2%) 3 (1%) Anemia 4 (2%) 2 (1%) Device related infection 4 (2%) 2 (1%) Less common adverse reactions in ≤ 1% of patients who received Smoflipid were dyspnea, leukocytosis, diarrhea, pneumonia, cholestasis, dysgeusia, increased blood alkaline phosphatase, increased gamma-glutamyltransferase, increased C-reactive protein, tachycardia, liver function test abnormalities, headache, pruritis, dizziness, rash and thrombophlebitis. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Smoflipid in countries where it is registered. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. Infections and Infestations: infection Respiratory, Thoracic and Mediastinal Disorders: dyspnea

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION For intravenous infusion only into a peripheral or central vein. (2.1) Recommended dosage depends on age, energy expenditure, clinical status, body weight, tolerance, ability to metabolize, and consideration of additional energy given to the patient. (2.4) The usual daily dosage in adults is 1 to 2 grams/kg per day and should not exceed 2.5 grams/kg per day (2.4) 2.1 Administration Instructions Smoflipid is for central or peripheral intravenous infusion. When administered with dextrose and amino acids, the choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of ≥ 900 mOsm/L must be infused through a central vein. Use a 1.2 micron in-line filter. Use a dedicated line for parenteral nutrition (PN). Smoflipid can be infused concurrently into the same vein as dextrose-amino acid solutions (as part of PN) by a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps. To prevent air embolism, use a non-vented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible bags in series, fully evacuate residual gas in the bag prior to administration, do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the bag runs dry. Do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer. 2.2 Instructions for Use After removing the overpouch, Smoflipid should be used immediately. If not used immediately, the product should not be stored longer than 24 hours at 2° to 8°C (36° to 46°F). After removal from storage, the emulsion should be infused within 24 hours. instructions instructions instructions instructions instructions 2.3 Admixing Instructions Prepare the admixture in PN containers using strict aseptic techniques to avoid microbial contamination. Do not add Smoflipid to the PN container first; destabilization of the lipid may occur. Smoflipid may be mixed with amino acid and dextrose injections to produce “all-in-one” PN admixtures. The following proper mixing sequence must be followed to minimize pH-related problems by ensuring that typically acidic dextrose injections are not mixed with lipid emulsions alone: Transfer dextrose injection to the PN container. Transfer amino acid injection. Transfer Smoflipid. Simultaneous transfer of amino acid injection, dextrose injection, and Smoflipid to the PN container is also permitted. Use gentle agitation during admixing to minimize localized concentration effects; shake bags gently after each addition. Do not inject additives directly into Smoflipid. Additions to the PN admixtures should be evaluated by a pharmacist for compatibility. Questions about compatibility may be directed to Fresenius Kabi USA, LLC. If it is deemed advisable to introduce additives, use strict aseptic techniques to avoid microbial contamination. The prime destabilizers of emulsions are excessive acidity (such as a pH < 5) and inappropriate electrolyte content. Amino acid solutions exert buffering effects that protect the emulsion from destabilization. Give careful consideration to the addition of divalent cations (Ca++ and Mg++), which have been shown to cause emulsion instability. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect the admixture to ensure that: precipitates have not formed during preparation of the admixture, and the emulsion has not separated. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. Discard the admixture if any of these are observed. The remaining contents of a partly used bag must be discarded. Infuse admixtures containing Smoflipid immediately. Admixtures should be used promptly with storage under refrigeration at 2° to 8°C (36° to 46°F) not to exceed 24 hours and must be infused completely within 24 hours after removal from refrigeration. 2.4 Adult Dosing Information The dosing of Smoflipid depends on the patient’s individual energy requirements influenced by age, body weight, tolerance, clinical status, and the ability to eliminate and metabolize lipids. When determining dose, energy supplied by dextrose and amino acids from PN, as well as energy from oral or enteral nutrition, has to be taken into account. Energy and lipid provided from lipid-based medications should also be taken into account (e.g., propofol). Prior to administration of Smoflipid, correct severe fluid and electrolyte disorders. Smoflipid contains 0.163 to 0.225 mg/mL of all-rac-α-tocopherol. The daily US recommended dietary allowance (RDA) in adults for α-tocopherol (Vitamin E) is 15 mg. Take into account the amount of α-tocopherol in Smoflipid when determining the need for additional supplementation. Recommended Adult Dosing The recommended dosage of Smoflipid for adult patients is 1 to 2 grams/kg per day and should not exceed 2.5 grams/kg per day.1 The initial rate of infusion should be 0.5 mL/min for the first 15 to 30 minutes of infusion. If tolerated, gradually increase until reaching the required rate after 30 minutes. Maximum infusion rate should not exceed 0.5 mL/kg/hour. The daily dose should also not exceed a maximum of 60% of total energy requirements [see Overdosage (10)]. The recommended duration of infusion for Smoflipid is between 12 and 24 hours, depending on the clinical situation. The administration flow rate is determined by dividing the volume of lipid by the duration of the infusion. Before starting the infusion, determine serum triglyceride levels to establish the baseline value. In patients with elevated triglyceride levels, initiate Smoflipid at a lower dosage and advance in smaller increments, monitoring the triglyceride levels with each adjustment [see Warnings and Precautions (5.8, 5.9)].
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on risks associated with Smoflipid when used in pregnant women. Animal reproduction studies have not been conducted with Smoflipid. It is not known whether Smoflipid can cause fetal harm when administered to a pregnant woman. Consider the benefits and risks of Smoflipid when prescribing to a pregnant woman. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Severe malnutrition in a pregnant woman is associated with preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations, and perinatal mortality. Parenteral nutrition should be considered if the pregnant woman’s nutritional requirements cannot be fulfilled by oral or enteral intake. 8.2 Lactation Risk summary No data are available regarding the presence of Smoflipid in human milk, the effects on the breast fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Smoflipid, and any potential adverse effects on the breastfed infant from Smoflipid, or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of Smoflipid have not been established in pediatric patients. Deaths in preterm infants after infusion of intravenous lipid emulsion have been reported [see Warnings and Precautions (5.1)]. Because of immature renal function, preterm infants receiving prolonged treatment with Smoflipid may be at risk of aluminum toxicity [see Warnings and Precautions (5.6)]. Patients, including pediatric patients, may be at risk for PNALD [see Warnings and Precautions (5.6)]. There are insufficient data from pediatric studies to establish that Smoflipid injection provides sufficient amounts of essential fatty acids (EFA) in pediatric patients. Pediatric patients may be particularly vulnerable to neurologic complications due to EFA deficiency if adequate amounts of EFA are not provided [see Warnings and Precautions (5.9)]. In clinical trials of a soybean oil-based intravenous lipid emulsion product, thrombocytopenia in neonates occurred (less than 1%). Smoflipid contains soybean oil (30% of total lipids). 8.5 Geriatric Use Energy expenditure and requirements may be lower for older adults than younger patients. Of the 354 patients in clinical studies of Smoflipid, 35% were > 65 years of age and 10% were > 75 years of age. No overall differences in the safety and efficacy of Smoflipid were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity in some older patients cannot be ruled out. 8.6 Hepatic Impairment Parenteral nutrition should be used with caution in patients with hepatic impairment. Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive parenteral nutrition, including cholestasis, hepatic steatosis, fibrosis and cirrhosis (parenteral nutrition associated liver disease), possibly leading to hepatic failure. Cholecystitis and cholelithiasis have also been observed. The etiology of these disorders is thought to be multifactorial and may differ between patients. Monitor liver function parameters closely. Patients developing signs of hepatobiliary disorders should be assessed early by a clinician knowledgeable in liver diseases in order to identify causative and contributory factors, and possible therapeutic and prophylactic interventions.


7 DRUG INTERACTIONS Coumarin and Coumarin Derivatives, Including Warfarin: Anticoagulant activity may be counteracted; monitor laboratory parameters. (7.1) 7.1 Coumarin and Coumarin Derivatives No drug interaction studies have been performed with Smoflipid. Soybean oil and olive oil have a natural content of vitamin K1 that may counteract the anticoagulant activity of coumarin and coumarin derivatives including warfarin. Monitor laboratory parameters for anticoagulant activity in patients who are on both Smoflipid 20% and coumarin or coumarin derivatives.

More information

Category Value
Authorisation number NDA207648
Agency product number 6UYK2W1W1E
Orphan designation No
Product NDC 63323-820
Date Last Revised 02-05-2016
Marketing authorisation holder Fresenius Kabi USA, LLC
Warnings WARNING: DEATH IN PRETERM INFANTS Deaths in preterm infants after infusion of intravenous lipid emulsions have been reported in the medical literature. Autopsy findings included intravascular fat accumulation in the lungs. Preterm infants and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. [See Warnings and Precautions (5.1) and Use in Specific Populations (8.4)] WARNING: DEATH IN PRETERM INFANTS See full prescribing information for complete boxed warning. Deaths in preterm infants have been reported in literature. (5.1, 8.4) Autopsy findings included intravascular fat accumulation in the lungs. (5.1,8.4) Preterm and low-birth-weight infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. (5.1, 8.4)