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. ( 2.5) The usual daily dosage in adults is 1 to 2 grams/kg per day and should not exceed 2.5 grams/kg per day ( 2.5) Smoflipid Pharmacy Bulk Package is only indicated for use in pharmacy admixture program for the preparation of three-in-one or total nutrition admixtures (TNAs) ( 2.3) 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 Smoflipid 1000 mL is supplied as a Pharmacy Bulk Package for admixing only and is not for direct infusion. Prior to administration, transfer to a separate PN container [see Dosage and Administration ( 2.3)]. 2.2 Instructions for Use Inspect the integrity indicator (Oxalert ®) (A) before removing the overpouch. Discard the product if the indicator is black. Place the bag on a clean, flat surface. Remove the overpouch by tearing at the notch and pulling down along the container. The Oxalert sachet (A) and the oxygen absorber (B) should be discarded. Inspect the bag and contents prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect Smoflipid to ensure that the emulsion has not separated. The lipid emulsion should be a homogenous liquid with a milky appearance. Discard the bag if there appears to be a phase separation of the emulsion, or if any signs of discoloration, particulates, and/or leakage are observed. Break off the BLUE infusion port cap with the arrow pointing away from the bag. NOTE: Choose a nonvented infusion set or close the air vent on a vented set. Follow the instructions for use for the infusion set. Use infusion sets (according to ISO Number 8536-4) with an external spike diameter of 5.5 to 5.7 mm. Use a 1.2 micron in-line filter during administration. Hold the base of the infusion port. Insert the spike through the infusion port by rotating your wrist slightly until the spike is inserted. Hang the bag using the hanger cut For Single Use Only Discard unused portion. Smoflipid 100 mL, 250 mL and 500 mL Flexible Containers After removing the overpouch, infuse 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, infuse within 24 hours. Figure Figure Figure Figure Figure 2.3 Preparation of Pharmacy Bulk Package Smoflipid 1000 mL Pharmacy Bulk Package is for admixing use only. It is not for direct intravenous infusion. Prior to administration, transfer to a separate PN container for individual patient use. Use the Pharmacy Bulk Package only in a suitable work area such as a laminar flow hood or an equivalent clean air compounding area. Do not pierce infusion port more than once. Transfer the contents through the blue infusion port using a suitable sterile transfer device or dispensing set. Discard any unused contents. Use the Pharmacy Bulk Package immediately for admixing after removal from overpouch. If not used immediately, the product can be stored for up to 24 hours at 2° to 8°C (36° to 46°F). After removal from storage, and once the closure is penetrated, use Pharmacy Bulk Package contents within 4 hours. [see Dosage and Administration ( 2.4)] . 2.4 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; follow automated compounding device instructions as indicated. 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 at 1-800-551-7176. 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. If not used immediately, store admixtures under refrigeration at 2° to 8°C (36° to 46°F) not to exceed 24 hours. Infusion must be complete within 24 hours after removal from refrigeration. Discard any remaining admixture. 2.5 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)].